NEWS - TABLE OF CONTENTS 2006

BACK TO ENTIRE TABLE OF CONTENTS (2007 - 1972)

May, 2007
(31 May) Humans have a bit of shark in them
(30 May) Researchers discover gene essencial to cerebellum formation
(25 May) Astrophysicists Find Fractal Image Of Sun's 'Storm Season' Imprinted On Solar Wind
(23 May) How Google wants to know everything about you [Searching in your Junk?
(17 May) Genome Is Larger and More Complex Compared to Fruit Fly and Mosquito Species That Carries Malaria
(15 May) Rosetta Genomics Receives First Ever Patent Supporting MicroRNA-Based Diagnostics and Therapeutics
(12 May) [Viral microRNA] - Cancer Virus' Genetic Targets Identified
(11 May) Is the universe a fractal? [With the DNA no exception to the universe? - AJP]
(10 May) Opossum Provides Insight into Human Evolution
(08 May) [Los Alamos] Genome Institute Reaches Milestone with a Mighty Microbe [to neutralize Uranium pollution]
(02 May) The Next Human Genome Project: Our Microbes [MetaGenomics and PostGenetics; Common computer algorithms]

April, 2007
(30 Apr) MicroRNA found in unicellular organism
(28 Apr) Mouse microRNA knockout uncovers critical roles in immune system
(26 Apr) Japanese Tohoku University International Innovation Forum in Silicon Valley, California
(25 Apr) Cure for Alzheimer's: Japanese Vaccine Works On Mice
(24 Apr) [Eric Mathur] named vice president of the J. Craig Venter Co. [La Jolla]
(23 Apr) 'Junk' DNA now looks like powerful regulator, Stanford researcher finds
(20 Apr) Could US scientists get EU funding?
(20 Apr) MicroRNAs Debut [at NIH] as Key Actors in Health and Disease
(14 Apr) Genomicists Tackle the Primate Tree
(12 Apr) J. Craig Venter Institute Announces Management Team and Organizational Structure
(12 Apr) Internationally Known Scientist [Claire Fraser-Liggett] to Head Institute of Genome Sciences at [University of Maryland] School of Medicine
(10 Apr) Scientists reveal structure of gateways to gene control
(05 Apr) Is Biology Reducible to the Laws of Physics? [Philosophy of PostGenetics is to come]
(02 Apr) Trillion-dollar prize turns dotcom into watt-com
(02 Apr) 'Junk DNA' Offers Up Prostate Cancer Clues
(02 Apr) Cancer epigenomics: DNA methylomes and histone-modification maps

March, 2007
(25 Mar) An Introduction to Synthetic Biology

(25 Mar) Biofuels launch biotech's 'third wave'
(25 Mar) Microsoft Goes Bio
(24 Mar) A Tiny Knock Out [effect of "knock out microRNA"]
(23 Mar) MetaGenomics: Ocean Study Yields a Tidal Wave of Microbial DNA [Dawn of Scientific PostDarwinism]
(15 Mar) Copy number linked to autism [a growing shift of focus towards PostGenetics]
(12 Mar) A [fractal] theory with the potential to unify all of biology
(12 Mar) Bucking the Zeitgeist - What happens when biologists and a physicist try to create a grand unifying theory of biology?

(10 Mar) Researchers Create Bacterial DNA Memory [The "Triple Helix" of "Biotech-Nanotech-Infotech" is complete]
(09 Mar) Rosetta Genomics underwriters exercise green shoe option [If the genome is a goldmine, where is the gold?]
(07 Mar) Little genomes for big dinosaurs [C-value fractal interpretation]
(05 Mar) Alnylam and Isis Announce Allowance of First U.S. Patent Covering Human microRNAs
(04 Mar) Netherlands Genomics Initiative: Strategic Plan 2008 - 2012: additional € 298 million public investment
(03 Mar) Microsatellite Instability and EGFR Testing in Colorectal Cancer ['Junk' repairs DNA?]
(02 Mar) Non-coding RNAs: lessons from the small nuclear and small nucleolar RNAs

February, 2007
(28 Feb) Study moves chimp-human split to 4 million years ago

(25 Feb) Biotech specialist hits near-record $570m
(23 Feb) Killing The Messenger RNA -- But Which One?
(21 Feb) LS9 Launched to Create Renewable Petroleum(TM) Biofuels [Khosla and MIT-Harvard-Stanford into Synthetic Biology]
(18 Feb) News Analysis: UC’s Biotech Benefactors [Biofuels or "H2 Economy"?]
(14 Feb) What is the purpose of noncoding DNA? [Wired beats Scientific American - Open letter to Sydney Brenner]
(12 Feb) What is junk DNA, and what is it worth?
(11 Feb) Stratagene Acquires Rights To microRNA Sequences
(09 Feb) Which genome variants matter? [What really matters may be the algorithm...]
(08 Feb) Pharma giants grab piece of RNAi pie
(08 Feb) Abingworth co-drives £9m Dutch fundraising [Abingworth pitches to corner the "junk" DNA market?]
(07 Feb) China Planning Major Investment in Biotech R&D
(04 Feb) Abingworth raises Europe’s largest ever life sciences venture fund
(04 Feb) High-density tiling array reveals introns and extensive regulation of splicing
(01 Feb) New Life for "Junk" DNA

January, 2007
(28 Jan) [Antigene RNA] Novel laboratory technique nudges genes into activity
(28 Jan) A windfall for RNA
(27 Jan) BIG PHARMA consolidates for PostGenetics; PFIZER, GLAXOSMITHKLINE, BRISTOL-MYERS SQUIBB
(24 Jan) Mapping the human genome wasn't enough. Venter is trying to create a microbe to free us from additiction to oil
(24 Jan) Genetic cause of schizophrenia proposed
(22 Jan) AVEO [USA] acquires rights to anti-cancer compound from MITSUBISHI PHARMA [JAPAN] [The anti-cancer revolution marches on]
(21 Jan) 'Quiet revolution' may herald new RNA therapeutics
(19 Jan) Google-funded genetic start-up?
(17 Jan) BioDiscovery Joins Microsoft BioIT Alliance [How about GOOGLE?]
(12 Jan) Micro[RNA] Molecules Can Identify Pancreatic Cancer
(11 Jan) ASURAGEN Licenses Yale miRNA Inventions with Potential in Lung Cancer
(10 Jan) NMC Group to set up facility at DuBiotech [put Dubai on the map of PostGenetics]
(06 Jan) Renegade RNA: Clues To Cancer And Normal Growth
(05 Jan) Improved Quarter for Biotech on Capital Markets ... and Financings and Partnering Deals Remain Red Hot
(04 Jan) SIRNA's Shaky Shareholder Settlement Sheds Light on MERCK Acquisition
(03 Jan) How Do MicroRNAs Regulate Gene Expression?
(02 Jan) The Evolution of Junk DNA from mostly Non-functional to Mostly Functional

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Humans have a bit of shark in them

Jennifer Viegas
Discovery News

Some 450 million years ago, sharks and humans shared a common ancestor, making sharks our distant cousins.

And according to recent research, this kinship is evident in our DNA, as at least one shark species possesses several genes that are nearly identical to those in humans.

The elephant shark's genome is so similar to ours that we wind up having more in common with it, genetically speaking, than with other species, such as teleost (bony skeleton) fishes, which are nearer to us on the evolutionary tree.

"This was a surprising finding, since teleost fish and humans are more closely related than the elephant shark is to humans," says lead author Associate Professor Byrappa Venkatesh.

Venkatesh, principal investigator at the Institute of Molecular and Cell Biology in Singapore, and his team determined that sets of genes on chromosomes, as well as actual genetic sequences, are "highly similar in the elephant shark and human genomes".

The researchers not only analysed the elephant shark genome, but also the genes for other animals including puffer fish, chickens, mice and dogs.

Their findings were recently published in the journal PLoS Biology.

The researchers identified 154 genes in humans that have comparable matches in mice, dogs and elephant sharks.

The similarities between people, mice and dogs were expected, given that they are all mammals.

But sharks are cartilaginous fish that seem to bear little physical resemblance to mammals...

Immunune system genes

The researchers also found that shark and human immune systems are very similar, since sharks have all four types white blood cells found in mammals.

Sean Van Sommeran, executive director of the Pelagic Shark Research Foundation in California, says that he was not entirely surprised to learn about the shark-human links.

"The field of genetics is a Pandora's box," Van Sommeran says.

[This and the following article are grouped - since the Cerebellum appeared in the emergence of species with the sharks. Therefore, evolutionary and comparative PostGenetics ("Genomics beyond Genes") may consider the entire genomes (and specific sets of genes) but also may "zoom" on well-identified neuronal networks and even cell(s), the Purkinje neuron, as its development is governed by "similar" (not identical) genomic information. - Pellionisz, 31st of May, 2007]

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Researchers discover gene essencial to cerebellum formation

By Institute for Research in Biomedicine (IRB)

A study published this week in the scientific journal PNAS provides new information on the origin of different cells in the cerebellum, an important component of the central nervous system found in all vertebrates, including humans, and the part of the brain that controls movement. The study was completed by researchers from the Institute for Research in Biomedicine (IRB Barcelona), the Department of Cell Biology of the University of Barcelona (UB), the IMIM-Hospital del Mar, Pompeu Fabra University (UPF) and Vanderbilt University (Nashville, Tennessee, USA). The main authors of the study are Dr. Marta Pascual (IRB Barcelona and UB) and Ibane Abasolo (IMIM-Hospital del Mar-UPF).

Co-author of the study, Francisco X. Real, coordinator of the Research Unit on Cell and Molecular Biology at IMIM-Hospital del Mar and Professor at the UPF, explains that this discovery sheds new light on the mechanisms of brain formation and has potential future applications for regenerative medicine. It provides crucial insight into the manipulation of truncal nerve cells (or stem cells) and their selective differentiation into 'gabergic' neurons, or cells that contain the neurotransmitter gamma-aminobutyric acid (GABA) and that act as inhibitors.

Eduardo Soriano, Principal Investigator of the Developmental Neurobiology and Regeneration laboratory at IRB Barcelona, and professor at the UB, maintains that the study explains two important principles: first, that the protein Ptf1a/p48 is needed for the production and differentiation of Purkinje neurons, the most important cells in the cerebellum; and second, that in the absence of this protein, the progenitor cells that should produce Purkinje neurons do not differentiate correctly and instead produce a different type of neuron, granular cells, indicating that Ptf1a/p48 acts as a molecular switch.

The researchers hypothesized that a transcription factor, whose function is well known in the pancreas and which appears to play a role in the nervous system, is also involved in the development of the cerebellum. In order to test their idea, and characterize the new mechanism of cell differentation, the authors used mice with a disactivated gene that codes for the Ptf1a/48 protein, and compared them with mice that express the gene normally. Their conclusions provide new insight into origin of nerve cells that form the cerebellum in higher organisms.

In a second research project, led by Francisco Real and Eduardo Soriano and funded by the Fundació La Caixa, the scientists aim to explore the potential of this gene to produce Purkinje neurons in a laboratory setting. The researchers will investigate whether the expression of Ptf1a/p48 can induce the production of Purkinje cells from stem cells and neurospheres, progenitor cells of adult neurons. This study is an important step toward understanding rare diseases, such as cerebellar ataxias, which is characterized by the degeneration of Purkinje cells. Producing this type of cell in the lab may lead to future neuronal replacement therapy.

[This author opened the "Pandorra box" of POSTgenetics (Genomics beyond Genes) by making experimentally verified quantitative predictions for the cerebellar Purkinje cells in the fugu fish, as compared to zebra fish and mammals such as the guinea pig, mouse and human. It would be most interesting to see if/how ptf1 is found in the newly sequenced elephant shark and how the arborization of the Purkinje neuron of the cerebellum of elephant shark would appear - Comment by A. Pellionisz, 31st of May, 2007]

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Astrophysicists Find Fractal Image Of Sun's 'Storm Season' Imprinted On Solar Wind

Source: University of Warwick
Date: May 25, 2007

[Our Sun found to be fractal (left), algorithmically fractal planets, Earth from the Moon - and a real bacterium showing fractality ... AJP]

Science Daily — Plasma astrophysicists at the University of Warwick have found that key information about the Sun’s 'storm season’ is being broadcast across the solar system in a fractal snapshot imprinted in the solar wind. This research opens up new ways of looking at both space weather and the unstable behaviour that affects the operation of fusion powered power plants.

Fractals, mathematical shapes that retain a complex but similar patterns at different magnifications, are frequently found in nature from snowflakes to trees and coastlines. Now Plasma Astrophysicists in the University of Warwick’s Centre for Fusion, Space and Astrophysics have devised a new method to detect the same patterns in the solar wind.

The researchers, led by Professor Sandra Chapman, have also been able to directly tie these fractal patterns to the Sun’s ‘storm season’. The Sun goes through a solar cycle roughly 11 years long. The researchers found the fractal patterns in the solar wind occur when the Sun was at the peak of this cycle when the solar corona was at its most active, stormy and complex – sunspot activity, solar flares etc. When the corona was quieter no fractal patterns were found in the solar wind only general turbulence.

This means that fractal signature is coming from the complex magnetic field of the sun.

This new information will help astrophysicists understand how the solar corona heats the solar wind and the nature of the turbulence of the Solar Wind with its implications for cosmic ray flux and space weather.

These techniques used to find and understand the fractal patterns in the Solar Wind are also being used to assist the quest for fusion power. Researchers in the University of Warwick’s Centre for Fusion, Space and Astrophysics (CFSA) are collaborating with scientists from the EURATOM/UKAEA fusion research programme to measure and understand fluctuations in the world leading fusion experiment MAST (the Mega Amp Spherical Tokamak) at Culham. Controlling plasma fluctuations in tokamaks is important for getting the best performance out of future fusion power plants.

The research by K.Kiyani, S. C. Chapman, B. Hnat, R. M. Nicol, is entitled "Self- similar signature of the active solar corona within the inertial range of solar wind turbulence" and was published on May 18th 2007 in Phys. Rev. Lett.

[Suppose that Mandelbrot was right and the "Universe is Fractal" ("Fractal Geometry of Nature"). Living organisms demonstrably can be modeled as fractals (trees, "brain cell arborizations"). Soon, it will be "obvious" that fractality of DNA causes fractality that it governs to grow (FractoGene). Understanding the fractality of the Sun brings closer nuclear fusion plans to reality. Understanding diseases caused by fractal defects of DNA (see FractoGem) brings closer diagnosis and therapy of "Junk DNA diseases" by Big Pharma, and puts Bioenergy, Nanotechnology and Infotech applications on mathematical (software-enabling) foundation - Comment by A. Pellionisz, 25rd of May, 2007]

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How Google wants to know everything about you [Searching in your Junk?]

From Times OnlineMay 23, 2007

Google wants to monitor the queries each individual taps into its search site to advise them on their life decisions

Rhys Blakely

Google says it does not yet “know enough about you” and is stepping up its efforts to collect personal information on the web.

Eric Schmidt, the Google chief executive, said yesterday that the world’s biggest internet search engine is still at a “very early” stage when it comes to gathering your personal data through the web. “This is the most important aspect of Google's expansion,” he added.

He envisaged a day when Google would be able to advise its users on everything from their career moves to how they should spend their free time, based on the collected queries they tap into Google.com.

Google already holds a vast amount of personal information about its users – ranging from the contents of e-mail (from its Gmail service) to credit card details (through Google checkout, its online payment system). The information is held in a vast network of massive “server farms” – the company's fleet of digital data centres into which it is estimated to have pumped billions of dollars.

Such information is key to success in the online advertising industry, the source of Google's massive wealth. The No1 aim is to build up precise portraits of individual consumers to better target campaigns.

As it seeks to broaden its information net, it emerged yesterday that Google is also backing a firm founded by the wife of Sergey Brin, the company’s billionaire co-founder, that aims to help people browse their genetic information online.

Google said the investment was made as the start-up 23andMe’s “goal of developing new ways to help people make sense of their genetic information will help us further our mission of organising the world’s information in this new and important field”.

Google invested about $4 million (£2 million) in the company, co-founded by Anne Wojcicki in 2006.

It is not alone among technology companies aiming to tap the human genome – perhaps the most personal information there is. Larry Ellison, the billionaire software behind Oracle, the database giant, last week told Times Online that he plans to store, track and manipulate consumers’ digital data – including their bank details, their medical records, even their genetic blueprints.

Health companies, for instance, given the opportunity to mine this information using Oracle technology, will be able to pinpoint the most effective drugs for individual patients, he suggested.

“We are getting close to this level of personalisation,” he said, citing work being done in Oracle’s labs.

On another front, applied to credit card and telephone records, a similar meeting of personal data and technology will help the authorities do a “better job in finding terrorists,” Mr Ellison said. The extension of predictive modeling techniques, already used to track markets on Wall Street, to areas such as healthcare “will help make societies more efficient,” he predicted.

Meanwhile, Autonomy, a Cambridge-based search technology specialist, has said it is exploring online “transaction hijacking”, where consumers buying items online are automatically informed, during their transaction, if a better price is offered elsewhere.

A Google spokesman stressed to Times Online that Mr Schmidt’s most recent comments referred only to the company’s web-search histories. Moreover, users have to opt in to Google's new "personalised search" tools and the company says it will not pass data on to third parties - unless ordered to do so by law.

Earlier this year, Google bowed to privacy concerns when it agreed to limit the time it keeps information about internet searches to two years.

However, the idea of Google – or any other company – taking a “big brother” role on the web will leave many civil libertarians feeling uneasy.

Data leaks have already sparked fears over personal information that can be gleaned from search behaviour. Last year, for instance, AOL, the internet portal that is part-owned by Google, accidentally released details of 20 million private search queries from 658,000 of its users to the online public.

The collection, quickly disseminated across the web by bloggers, provides a disturbingly intimate picture of some of AOL's user base. Alongside searches for Angelina Jolie and Britney Spears, darker queries typed into the AOL search engine included: "how to tell your family you're a victim of incest" and "how to kill your wife".

Potentially incriminating entries included: "cocaine in urine".

TechCrunch, a blog, said at the time: "The utter stupidity of this is staggering ... The data includes personal names, addresses, social security numbers and everything else someone might type into a search box."

[Phenotype profiling is fun - dating services and job hunting are based on profile matching. Genotype profiling is genuine, however, it is still in its infancy. "Genetic screening" is already widely practiced to reveal which couples would run a serious risk to reproduce together - where known glitches latent in both "would be parents" might result in unacceptable consequences. However, our "genic composition" is virtually identical - our "personality" (human diversity) is tied to our differences in the "Junk" DNA. People are much more interested in who are positively compatible, rather than who aren't. Is Google ready to take on the formidable scientific-technological challenge of "Searching in your Junk DNA"? - Comment by A. Pellionisz, 23rd of May, 2007]

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Genome Is Larger and More Complex Compared to Fruit Fly and Mosquito Species That Carries Malaria

Scientists at J. Craig Venter Institute Publish Draft Genome Sequence From Aedes aegypti, Mosquito Responsible for Yellow Fever, Dengue Fever

ROCKVILLE, Md., May 17 /PRNewswire-USNewswire/ -- The fight against yellow fever and dengue fever was advanced today by an international team of researchers led by Vishvanath Nene, Ph.D. of the J. Craig Venter Institute who sequenced the Aedes aegypti genome, the mosquito that carries these deadly diseases. The research was published in the journal "Science."

This research is the first characterization of the approximately 1.38 billion base pairs of DNA of the Ae. aegypti genome. From this sequence, the team showed that this mosquito species has an estimated 15, 419 protein encoding genes.

Since both the sequence of the fruit fly, Drosophila melanogaster (sequenced in 1999 and published in 2000) and another mosquito species, Anopheles gambiae, (sequenced and published in 2002) were available, researchers were able to compare these insects to Ae. aegypti to ascertain biological differences between the species.

An. gambiae diverged on the evolutionary tree from the fruit fly about 250 million years ago, and the two mosquito species diverged from one another approximately 150 million years ago. Genomic comparisons revealed greater differences between the fruit fly and the mosquito species, than between the two mosquito species.

An important finding from this analysis is the discovery of certain proteins and genes unique to the Ae. aegypti. These proteins and genes, among many things, infer robustness to the insect. A more thorough analysis of these genes and proteins may lead to improved means to eradicate the mosquito and thereby stop the spread of yellow and dengue fevers.

Another key discovery was that almost 50 percent of the genome consisted of transposable elements. These are movable pieces of DNA that cause mutations and can affect genome size. The researchers showed that likely due to these elements the gene length and the intergenic regions of Ae. aegypti are 4-6 times larger than those of An. gambiae and the fruit fly.

[Scientific American - notorious of their ill-understanding the field of "non-coding DNA" - breaks the same news under this totally misleading title:

Genetic Code of Deadly Mosquito Cracked

No. The genetic code has not been "cracked". The book has been "revealed", but still those thinking in terms of "junk DNA" can not read any of the 2.5 Billion letters but about the same number of genes that is also present from the lowliest creatures up to the genome of humans (1.3% in the human genome)].

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Rosetta Genomics Receives First Ever Patent Supporting MicroRNA-Based Diagnostics and Therapeutics

Company Expects Further Precedent Setting Issuances to Follow

REHOVOT, Israel and NORTH BRUNSWICK, New Jersey, May 15, 2007 /PRNewswire-FirstCall/ -- Rosetta Genomics, Ltd. (NASDQ: ROSG), a leading microRNA company, announced today that on May 15, 2007, the United States Patent and Trademark Office (USPTO) issued Rosetta Genomics U.S. Patent No. 7,217,807. This is the first microRNA composition of matter patent ever issued relating to a human or viral microRNA gene, and the company believes that this issuance sets an important precedent for Rosetta Genomics' entire target patent portfolio.

The patent covers composition of matter directed at a specific microRNA gene found in the Human Immunodeficiency Virus (HIV). The company believes that this patent, as well as the hundreds of other viral and human microRNA-related patent claims filed by the company worldwide, constitutes a broad intellectual property estate surrounding a new class of prospective drug targets with significant therapeutic opportunity. Targeting microRNAs provides the unique potential to either up- or down-regulate key disease causing proteins. The potential to up- or down-regulate protein expression broadly across this prospective target class is a significant advantage. Human and viral microRNA targets are expected to play a role in the regulation of key disease processes in major therapeutic areas such as oncology, metabolism and infectious diseases.

"This is truly a precedent setting event for validating our extensive portfolio in microRNA genes for both therapeutics and diagnostics," said Ranit Aharonov, Ph.D., Executive Vice President IP & Computational Biology at Rosetta Genomics Ltd. "Rosetta Genomics is the first commercial entity to receive a patent on a microRNA gene. Given we have another patent which has been allowed, and many others in active examination, we feel confident that we will continue to see issuances of our patents for both human and viral microRNA gene sequences as well as patents covering microRNA biomarkers and our cutting-edge enabling technologies. We view the USPTO's decision to issue this patent as strong validation of our position as a leader in this rapidly expanding field. "

"This is a landmark occasion for us", said Amir Avniel, President and CEO of Rosetta Genomics Ltd. "This is a significant step towards validating Rosetta Genomics' leadership role in terms of our microRNA intellectual property estate. Moreover, we believe the issuance of this patent, and future such patents, will allow exclusive partnership opportunities and increases the value proposition across our broad product development pipeline for microRNA-based diagnostics and therapeutics."

About microRNAs

MicroRNAs (miRNAs) are a recently discovered, naturally occurring form of RNAi. These small RNAs act as protein regulators and have the potential to form the basis for a new class of diagnostics and therapeutics. Since many diseases are caused by the abnormal activity of proteins, the ability to selectively regulate protein activity through microRNAs could provide the means to treat a wide range of human diseases. In addition, microRNA expression levels have been shown to be correlated with various disease states and to hold significant potential as diagnostics and prognostic markers

About Rosetta Genomics

Rosetta Genomics is a leader in the development of microRNA-based diagnostics and therapeutics. Founded in 2000, the company's integrative research platform combining bioinformatics and state-of-the-art laboratory processes has led to the discovery of hundreds of biologically validated novel human microRNAs. Building on its strong IP position and strategic alliances with leading biotechnology companies, Rosetta Genomics is working to develop a full range of diagnostic and therapeutic products based on microRNAs. The company's primary focus is in the development of microRNA-based products to diagnose and treat different forms of cancer and infectious diseases.

USPTO 7,217,807 Bioinformatically detectable group of novel HIV regulatory genes and uses thereof

The invention claimed is:

1. An isolated nucleic acid consisting of 77 up to 120 nucleotides, wherein the nucleic acid comprises the sequence of SEQ ID NO: 14.

2. An isolated nucleic acid wherein the sequence of the nucleic acid consists of the sequence of SEQ ID NO: 14.

3. A vector comprising an HIV nucleic acid insert, wherein the nucleic acid insert consists of the nucleic acid of claim 1 or claim 2, and wherein said vector does not comprise an HIV nucleic acid insert other than the nucleic acid of claim 1 or claim 2.

4. A probe comprising an HIV nucleic acid insert, wherein the nucleic acid insert consists of the nucleic acid of claim 1 or claim 2, and wherein said probe does not comprise an HIV nucleic acid insert other than the nucleic acid of claim 1 or claim 2.

5. An isolated nucleic acid complement of the nucleic acid of claim 1 or claim 2, wherein said isolated nucleic acid complement is identical in length to the nucleic acid of claim 1 or 2.

[The "PostGenetics Global Strategy" (to leapfrog "Genetics" and jumping directly into bioinformatics-driven intellectual property of non-coding genome information, in this case, microRNA-based) has been validated in small scale by New-Zealand born Australian pioneer Malcolm Simons' US-patents, based on which a $100 M Australian company was built over 20 years (GTG, with zero entanglement since 2001 of Dr. Simons). GTG, instead of developing strong US alliance, took the path of opposing potential US allies (stock GENE fell from top $14 to as low as $3, with current market cap $60 M).

The "Israeli validation" is real. Holding about half of known microRN-s in its portfolio the worth of an average microRNA is up from recent $150,000 to about $340,000. Based in Israel, their twin HQ is in the USA (New Jersey, home to scores of "Big Pharma"). With direct Israeli involvement in PostGenetics Founders (N. Tishby - his Ph.D. student Gill Bejerano, now Professor, amassing a stronghold in Stanford) any analyst could bet that Rosetta Genomics could, at any time, follow the model of Merck having acquired San Francisco-based SiRNA recently for $1.1 Billion. Prediction is, however, that ROSG will *not* sell out its golden egg even for more - it is quite explicit about building "strategic alliance" as a better venue. Central Europe's chances (with the exception of perhaps Estonia) are thus relatively weakened by not adopting at a critical time a winner global strategy. Next bet is Japan, watching carefully the spectacular rise of China (and in bioinformatics, even of India, South Korea and Singapore), thus Japan is expected to hedge its eminent position in "Big Pharma" by investing in PostGenetics. In Europe, The Netherlands are steadily re-trenching from a strong "Genetics" school to "PostGenetics" - and even Russia is in a "wake up" mode. - Comment by A. Pellionisz, 15th of May, 2007]

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[Viral microRNA] - Cancer Virus' Genetic Targets Identified

Science Daily — University of Florida researchers have identified specific human genes targeted by a virus believed to cause Kaposi's sarcoma, a rare form of cancer associated with AIDS and with organ transplants that causes patches of red or purple tissue to grow under people's skin.

Writing May 11 in PLOS Pathogens, the scientists are the first to name human genes that are actually hijacked by a virus wielding minimolecules called microRNAs. Apparently the viral microRNAs silence genes known to influence growth of blood vessels and suppress tumor cells. Scientists believe that with the regulatory genes sidelined, blood vessel growth runs rampant, resulting in the typical markings of Kaposi's sarcoma.

"The hallmarks of Kaposi's sarcoma are red spots full of blood vessels on the necks, arms and legs of patients," said Rolf Renne, Ph.D., an associate professor of molecular genetics and microbiology at the College of Medicine and a member of the UF Shands Cancer Center and the UF Genetics Institute. "We think that the tumor virus is using microRNAs to make sure infected cells are well nourished and protected from the human immune system."

Thought to be little more than cellular debris less than a decade ago, microRNAs are short chemical strands that strategically silence gene activity by binding to RNA within cells. They play a role in healthy development -- no one with a complete set of fingers and toes would want their genes to keep adding new digits -- and they evidently may be involved in the onset of some diseases, including cancer.

Now it seems that even foreign microRNA has a say in human health.

In an effort to identify human gene targets, UF scientists equipped cultured human cells with just 10 genes from the Kaposi's sarcoma virus, thus endowing human cells with the ability to produce viral microRNA. Scientists then screened the more than 30,000 genes that exist within human cells and found that 81 were strongly inhibited in the presence of the viral microRNA.

Five of the most affected genes are known to suppress tumor and blood vessel growth and influence the body's immune response, suggesting that the herpesvirus uses microRNA to create a cancerous environment in which it thrives, undetected by the body's natural defenses.

Researchers confirmed the results of the microRNA gene profiling with tests to detect individual microRNA activity in specific genes. "The data beautifully showed which genes were regulated by the viral microRNA," said Henry Baker, Ph.D., a professor and interim chairman of molecular genetics and microbiology who oversaw the gene screening. "The most exciting thing was one of the most-targeted genes on the list is thrombospondin 1. When something is important in a natural process, there are often a lot of built-in redundancies. In this case all of the viral microRNAs were used to target 34 different binding sites on the human gene, so apparently this is a virus that really wants to down-regulate thrombospondin."

ABSTRACT Kaposi sarcoma–associated herpesvirus (KSHV) is a gamma-herpesvirus associated with Kaposi sarcoma, primary effusion lymphoma, and a subset of muticentric Castleman disease. Recently, it was found that KSHV encodes 12 microRNAs (miRNAs) within its latency-associated region. miRNAs are small 22 nucleotide-long single-stranded RNA molecules that act to inhibit gene expression by binding to target messenger RNAs (mRNAs). Because miRNAs bind to these targets with limited base pairing, it has been difficult to find targets. The goal of our study was to identify cellular mRNAs targeted by KSHV-encoded miRNAs. Microarray analysis of cells expressing the KSHV miRNAs revealed a set of 81 genes that were changed. Several genes are regulators of important functions such as blood vessel growth, cell proliferation, and cell death. One target, thrombospondin 1, is a potent inhibitor of blood vessel growth and is known to be down-regulated in Kaposi sarcoma tumors. Thrombospondin 1, which is targeted by multiple miRNAs, also showed reduced protein levels in our study. To our knowledge, our data describe the first targets for tumorvirus-encoded miRNAs and suggest that these novel regulators may have roles in pathogenesis.

["Conventional wisdom" would dictate that microRNA-s are found in eukaryotes - not even in bacteria, e.g. not in Mycoplasma Genitalium. However, there is no "conventional wisdom" for microRNA-s since they are so novel in our (limited) set of knowledge. The 12 microRNA-s found by this pivotal study are in a VIRUS. Another "conventional wisdom" is that the so-called "Watson-Crick recombination" of A-T and C-G is necessary for binding with DNA. MicroRNA-s *don't* obey to such "absolutely fundamental" conventional wisdom. It is a challenge to PostGenetics to identify the "new wisdom" (beyond Genes) of these "non-coding" (formerly "junk") sequences - Comment by A. Pellionisz, 12th of May, 2007]

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Is the universe a fractal? [With the DNA no exception to the universe? - AJP]

09 March 2007
New Scientist

Written across the sky is a secret, a hidden blueprint detailing the original design of the universe itself.

The spread of matter throughout space follows a pattern laid out at the beginning of time and scaled up to incredible proportions by nearly 14 billion years of cosmic expansion.

Today that pattern is gradually being decoded by analysing maps of the distribution of the stars, and what has been uncovered could shake modern cosmology to its foundations. Cosmology is founded on the assumption that when you look at the universe at the vastest scales, matter is spread more or less evenly throughout space. Cosmologists call this a "smooth" structure.

But a small band of researchers, led by statistical physicist Luciano Pietronero of the University of Rome and the Institute of Complex Systems, Italy, argues that this assumption is at odds with what we can see.

Instead they claim that the galaxies form a structure that isn't smooth at all: some parts of it have lots of matter, others don't, but the matter always falls into the same patterns, in large and small versions, at whatever scale you look. In other words, the universe is fractal.

It is a controversial view, and one that sparked an intense debate over a decade ago. Since then, astronomers have surveyed ever-greater numbers of galaxies, taking larger and larger samples of the universe. Now the biggest galaxy survey ever and a brand new map of the universe's dark matter are adding fuel to the fire.

At stake is far more than the way galaxies cluster. A fractal universe could undermine cosmology's most basic assumptions. "All of the observations we make depend to a greater or lesser extent on the idea that the universe is homogeneous," says David Hogg of New York University, who leads a team of physicists that disputes Pietronero's view.

This idea that matter is spread more or less evenly throughout the universe is embodied in Einstein's cosmological principle. Einstein formulated it after publishing his general theory of relativity, which describes how the distribution of mass bends space-time and creates gravity. It allows cosmologists to use the equations of general relativity to describe the geometry of the whole universe. As a result it has led to a picture of a universe expanding uniformly from the big bang and in which cosmological measurements have defined meanings.

Fractals allow Pietronero to paint a very different sort of picture - one in which the irregular distribution of matter that we see around us never evens out into a smooth structure, but repeats itself at ever grander scales.

Fractals are familiar enough: we see them in the branching of trees, the curves of coastlines, lungs, turbulence and clouds. No matter what scale you look at them, fractal patterns look the same.

Think of broccoli: a tiny branch looks much the same as the whole vegetable. Zoom in or zoom out, the structure looks the same - exquisitely detailed, never smooth. Fractals can be beautiful to look at, but when it comes to galaxies it may be a subversive kind of beauty. Certainly the universe does not look smooth. Some regions contain clusters of matter; others are virtually empty.

Hundreds of billions of stars group together to form galaxies, and galaxies congregate in clusters. Clusters assemble into colossal structures called superclusters that can stretch out for 100 million light years and look uncannily like fractal patterns. Even superclusters string together in long filaments and sheets that stretch like ghostly cobwebs across an otherwise empty sky. The Sloan Great Wall, for example, which was discovered in 2003, spans more than a billion light years. These filaments and sheets seem to encircle huge voids of empty space. The voids range from 100 to 400 million light years in diameter, making the whole assemblage appear as an immense, glowing lattice punctuated by wells of darkness.

No one disputes that the universe is far from smooth on relatively small scales - by which cosmologists mean thousands of light years. But Hogg's team is convinced that if you zoom further out, smoothness reigns. "When you're looking at the size scales of galaxies, groups of galaxies, clusters, superclusters and filaments, it looks like a fractal," says Hogg. "But once you get larger than all of that, then it starts to look homogeneous."

What has convinced him is his team's analysis of the latest data from the Sloan Digital Sky Survey, the largest 3D map of the galactic universe so far. His team insists that the map is proof of smoothness.

The fractal camp, however, are skeptical. In fact, they say the Sloan observations confirm what they've been claiming all along. It might appear to be deadlock, but at least with the Sloan survey the two sides can agree what they're disagreeing about.

For years Pietronero and his team argued that the statistical methods mainstream cosmologists were using to establish homogeneity were flawed because they start off by assuming that matter is evenly spread. The team was mostly ignored until 2004, when Hogg and astrophysicist Daniel Eisenstein of the University of Arizona in Tucson spent a summer in Paris with Pietronero's colleagues, cosmologists Francesco Sylos Labini of the Enrico Fermi Centre and the Institute for Complex Systems, Rome, and Michael Joyce of the Pierre and Marie Curie University, Paris.

"We argued every day about fractals," Hogg says. "Those battles raged over lunch and coffee and finally convinced us by the end of our visit that we should be doing the analysis as they say." When they returned to the US, Hogg and Eisenstein applied the fractal team's methods to a sample of 55,000 luminous red galaxies mapped by Sloan.

They found that the galaxies do form a fractal pattern, but as they looked at bigger and bigger scales, the pattern appeared to disintegrate and smooth out at just over 200 million light years - a scale far larger than most cosmologists had expected.

But Pietronero and Sylos Labini are not convinced. Instead, they believe that if astronomers could continue to zoom out and look at even larger scales, they would find more clustering. They suspect that the apparent smoothness at 200 million light years is not real, but rather an illusion created by statistical effects due to the limited range of the Sloan survey. Hogg's team, though, insist that their evidence of homogeneity is statistically significant. "I think the result really is secure," says Hogg. "I would stake my scientific reputation on that."

Even if the result is real, mainstream cosmologists still have a huge problem on their hands. The fact that the fractal patterning extends to far bigger scales than anyone had expected means that there must be far bigger structures than anyone expected - structures that are even bigger than superclusters.

The fractal team argues that the standard model cannot explain the existence of these galactic giants. "If you look at the galaxy data, you can see enormous objects hundreds of millions of light years across, stuff that's really huge," says Pietronero.

"This is a huge problem. You're going to have to change the story very radically." The usual story runs something like this. In the tiny fluctuations of the nascent universe, matter began to collect in denser regions, setting off a chain reaction of gravitational collapse that has given us the large-scale structure we see today. Gravity has worked from the bottom up, building galaxies first, then collecting galaxies into clusters, then clusters into superclusters and so forth. But while the matter has been clumping together, the universe has been expanding, and thus a battle has ensued: gravity versus expansion.

According to Pietronero, there simply hasn't been enough time since the universe came into being 14 billion years ago for gravity to sculpt structures larger than about 30 million light years across: expansion would have prevented anything larger from forming. "The existence of structures much larger than this implies a crisis of the present view of structure formation," he says. This present view is the "cold dark matter model", in which the glowing masses of stars and galaxies are only the tip of the cosmic iceberg. Luminous matter makes up roughly 15 per cent of all the matter in the universe - the other 85 per cent is mysterious dark matter. Hogg's team says that the new observations do not undermine the standard view as Pietronero claims. Instead, they maintain that the cold dark matter model explains the Sloan data quite accurately. For that to be true, however, Hogg's team have to put a number called a bias parameter into their equations. It reflects the difference between the distribution of matter in computer simulations of the cold dark matter model and the observed distribution of luminous matter. Collisions between particles of ordinary matter help it clump together, but dark matter is thought not to behave in the same way. That suggests it could be spread out in space more evenly than ordinary matter, so cosmologists assume that the distribution of the matter we can see - galaxies, say - is not a true reflection of the distribution of all the matter that is out there.

They believe the structure of the universe is really much "smoother" than it appears to be, because dark matter dominates. In the case of the Sloan survey, the bias is 2: the visible galaxies are clumped twice as densely as the predicted total distribution of matter in the universe. Sylos Labini, however, sees the bias as a fudge that allows cosmologists to discount the observed clustering of galaxies and to assume that the gigantic clusters of superclusters are only half the problem they appear to be. "The bias is a way to hide the size of structures behind some ad hoc parameter," he says. Mainstream cosmologists, however, feel the bias is justified, assuming that galaxies cluster in regions of space that are replete with excess dark matter. According to the standard model, dark matter is everywhere, but galaxies only shine in the rare regions where dark matter is densest. Dark matter also lingers in the voids where no light shines but here it is thinly spread out. In other words, while the luminous galaxies look very clustered, the underlying blanket of dark matter is far smoother, supporting the claim of homogeneity. "If the cold dark matter model is correct, then there should be dark matter in the voids," Hogg says.

The million-dollar question is: what is the real distribution of dark matter?

Is dark matter smooth or fractal? Is it clustered like the galaxies, or does it spread out, unseen, into the great voids? If the voids are full of dark matter, then the apparent fractal distribution of luminous matter becomes rather insignificant. But if the voids are truly empty, the fractal claim requires a closer look. Astronomers are now providing our first glimpse into the voids and our first look at the pattern of invisible matter. Richard Massey of the California Institute of Technology in Pasadena and others in the Cosmic Evolution Survey project have just created the first 3D map of dark matter in the universe (New Scientist, 13 January, p 5). They were able to find the dark matter by observing its gravitational effect on any light streaming past it. Combining data from the Hubble Space Telescope, the Subaru telescope in Hawaii and the Very Large Telescope in Chile, they mapped the distribution of dark matter at scales ranging from 23 million to 200 million light years across. Massey's team found that the dark matter distribution is nearly identical to the luminous matter distribution. "The first thing that strikes me is the voids," Massey says. "Vast expanses of space are completely empty. The dark matter makes up a criss-crossing network of strings and sheets around these voids. And all the luminous matter lies within the densest regions of dark matter."

Although this distribution of dark matter seems to favour the idea that the universe is fractal, Hogg isn't convinced. "It is interesting," he says, "but measurements of dark matter are much less precise than measurements of galaxy distributions." "The result is very new," Massey agrees. "It demonstrates a very exciting new way of looking directly at dark matter and will be vital in future work, but hasn't yet been subject to all the analysis that has been applied to galaxy surveys." When asked if the dark matter exhibits an explicitly fractal structure, Massey replies, "We don't know yet."

"The universe is not a fractal," Hogg insists, "and if it were a fractal it would create many more problems that we currently have."

A universe patterned by fractals would throw all of cosmology out the window. Einstein's cosmic equations would be tossed first, with the big bang and the expansion of the universe following closely behind. Hogg's team feel that until there's a theory to explain why the galaxy clustering is fractal, there's no point in taking it seriously. "My view is that there's no reason to even contemplate a fractal structure for the universe until there is a physical fractal model," says Hogg. "Until there's an inhomogeneous fractal model to test, it's like tilting at windmills." Pietronero is equally insistent. "This is fact," he says. "It's not a theory." He says he is interested only in what he sees in the data and argues that the galaxies are fractal regardless of whether someone can explain why. As it turns out, there is one model that may be able to explain a fractal universe. The work of a little-known French astrophysicist named Laurent Nottale, the theory is called "scale relativity" (see "Fractured spacetime"). According to Nottale, the distribution of matter in the universe is fractal because space-time itself is fractal. It is a theory on the fringe, but if the universe does turn out to be fractal, more people might sit up and take notice. A resolution to the fractal debate will only come with more data. Sloan is currently charting more galaxies and will release a new map in the middle of 2008. According to Sylos Labini, this will cover over 650 million light years and should tell us if the apparent transition to homogeneity extends beyond 200 million light years. For now, the pattern of the world, imprinted at the origin of the universe, remains a secret glimpsed only in the knowing shimmer of the stars.

Fractured space-time

French astrophysicist Laurent Nottale has developed a theory that takes fractals to a whole new level. A researcher at the Meudon Observatory in Paris, Nottale set out to extend Einstein's principle of relativity - in which the laws of physics remain the same regardless of the motion of an observer - to a theory in which the laws of physics would remain the same regardless of the scale at which the universe is being observed. He found that the underlying space-time of such a theory would have to be fractal. In Nottale's theory, called scale relativity, the underlying fractality of space-time is most noticeable in the quantum world. Quantum behaviour, he claims, can be understood geometrically - particles move along fractal trajectories. On large scales, his model could explain a fractal pattern of the galaxies. The most profound question in physics today is how to unify the really small with the really big - and when it comes to matters of scale, fractals may turn out to be a key ingredient.

[My knowledge of the universe is almost nil; 40+ years of research and 3 Ph.D.-s in Computer Engineering, Biology, and Physics don't measure up to the universe. However, having devoted the most recent 7 years entirely to the deep study of the DNA, I have evidence that the DNA is fractal. Perhaps not surprisingly, since it is a rather conspicuous tiny part of the universe.

As for "roughness" or "smoothness" on different scales, my Neural Net pioneering concluded on the same result; that "coordinated movements" in the space-time domain are "smooth", but the cerebellar Purkinje neurons that actually do the coordination "in the really small" - are fractal (fractogene concept, followed up independently).

The simplest visualization that fractals are "a key ingredient" in connecting "smoothness" with "roughness", depending on the scale, is provided below by the example of the "oldest known fractal" ("Cantor dust" - around 1872). Each segment, if one focuses "on the small" is a "smooth" line. However, a "bigger picture", when segments of several sizes are considered together, the picture is "rough" - Comment by A. Pellionisz, 17th of May, 2007]

"Cantor Dust"; generated by "middle third deletion rule", are both "smooth" and "rough", depending on the subset considered [AJP]

[Julia set (left) and Milky way & Sun (right), Figures from IPGS Founder Jules Ruis - AJP]

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Opossum Provides Insight into Human Evolution

First Decoded Marsupial Genome Reveals "Junk DNA" Surprise

Stefan Lovgren

for National Geographic News

May 10, 2007

The genome of a marsupial—the tiny short-tailed opossum (Monodelphis domestica)—has been sequenced for the first time.

The study reveals a surprising role in human evolution for "jumping genes"—parasitic bits of "junk DNA" that until now were thought to be nothing more than a nuisance—and may also lead to a number of medical breakthroughs.

In particular, the study highlights the genetic differences between marsupials such as opossums and kangaroos and placental mammals like humans, mice, and dogs.

Marsupials typically spend their youths tucked in a mother's pouch, while placental females maintain a temporary organ called the placenta to nourish their embryos.

"The opossum is a wonderful comparison to the human," said Eric Lander, director of the Broad Institute of MIT and Harvard University in Cambridge, Massachusetts, which led the sequencing project.

The study, which appears in today's issue of the journal Nature, helps to explain the evolutionary origins of human DNA, Lander pointed out. (Read a genetics overview.)

And opossums are often used as models in a wide variety of research on human health and disease, including the malignant melanoma form of skin cancer. (Related: Macaque Genome Deciphered; May Herald Medical Breakthroughs" [April 12, 2007].)

The new findings show that marsupials have a much more complex immune system than previously thought.

Jumping Genes

Marsupials are the closest living relatives of placental mammals. The two groups split from a common ancestor about 180 million years ago.

Scientists were able to pinpoint the genetic elements that are present in placental mammals but missing from marsupials to learn more about what makes the two groups different.

The researchers were surprised to find that placental and marsupial mammals have largely the same set of genes for making proteins. Instead, much of the difference lies in the controls that turn genes on and off.

"Twenty percent of all the regulatory instructions in the human genome were invented after we part ways with the marsupials," Lander said.

"That was the first really important surprise about evolution—it's tinkering much more with the controls than it is with the genes themselves."

The scientists were also surprised to find that these regulatory sequences have in large part been distributed across the human genome by so-called jumping genes.

These genes have hopped through chromosomes for more than a billion years, leaving behind many copies of themselves. So until now the genes had been widely regarded by scientists as parasites, or "junk DNA," that played no creative role in evolution.

"It was a surprise that quite a significant proportion of all the new regulatory controls in the genome were coming from jumping genes," Lander said.

"It looks like [they are] a pretty major force for evolutionary innovation."

Advanced Immune System

The short-tailed opossum is native to South America and is also known as the Brazilian opossum and rain forest opossum.

The individual whose genome was sequenced came from a colony housed at the Southwest Foundation for Biomedical Research in San Antonio, Texas.

The animals have many features that make them ideal for scientific research, especially during early development, experts point out.

"Their biology is fascinating," said Jenny Grace, a biologist and marsupial expert at the Australian National University (ANU) in Canberra.

"Their young are born very tiny, the size of a penny."

The creatures are the only other mammals known to develop melanoma skin cancer solely from exposure to ultraviolet light, the cause of melanoma in most human cases.

Newborn opossums can also repair damage to their spinal cords, making them a focus of research into regenerative medicine.

"This shows us that it may not be that hard to grow spinal cords," said Lander, the Broad Institute director.

"Once you have a marsupial that can do something that a human or mouse can't do, you can compare the two," he added. "We're saying, wait, wait, it may not be that hard to grow spinal cords. Our closest cousins can do it. Let's see what tricks [they] have."

Scientists had also believed that marsupials have a primitive immune system.

"The genome project knocked that firmly on its head," ANU's Grace said.

"It turns out that marsupials have a very complicated immune system. It's just different from us."



Thursday, May 10, 2007

Led by researchers from Harvard and MIT, a team of scientists sequenced the DNA of the gray South American short-tailed opossum -- the first marsupial to have its genome sequenced.

Marsupials are closely related to placental mammals, the group that includes humans, but their evolutionary lines diverged 180 million years ago during the dinosaur age.

Interestingly, the team found that the majority of differences were found not in genes coding for proteins, but in the non-coding regions that has been popularly described as "junk DNA".

A fifth of the human genome's key functional elements arose after the divergence from marsupials, the research found. Most of these innovations occurred not in protein-coding genes but in areas of the genome that do not contain genes and until recently [until International PostGenetics Society formally abandoned the misnomer "Junk" DNA - AJP] had been derided as junk DNA, they found.

[Science Daily] ... It has been the regulation of their genes - when they turn on and off - that has changed dramatically.

"Evolution is tinkering much more with the controls than it is with the genes themselves," said Broad Institute director Eric Lander. "Almost all of the new innovation ... is in the regulatory controls. In fact, marsupial mammals and placental mammals have largely the same set of protein-coding genes. But by contrast, 20 percent of the regulatory instructions in the human genome were invented after we parted ways with the marsupial."

The research, released Wednesday (May 9) also illustrated a mechanism for those regulatory changes. It showed that an important source of genetic innovation comes from bits of DNA, called transposons, that make up roughly half of our genome and that were previously thought to be genetic "junk."

The research shows that this so-called junk DNA is anything but, and that it instead can help drive evolution by moving between chromosomes, turning genes on and off in new ways.

The research - the first time a marsupial genome was decoded - involved the gray, short-tailed opossum, a native of South American rain forests that is small enough to fit in the palm of one's hand. Marsupials, which include kangaroos and koalas, have young that do much of their development in a pouch outside the mother's body instead of in an interior womb as in humans and other "placental mammals."


It had been initially thought that most of a creature's DNA was made up of protein-coding genes and that a relatively small part of the DNA was made up of regulatory portions that tell the rest when to turn on and off.

As studies of mammalian genomes advanced, however, it became apparent that that view was incorrect. The regulatory part of the genome was two to three times larger than the portion that actually held the instructions for individual proteins.

"The official textbook picture of how genes work really didn't appear to be right," Lander said. "There was much more of the genome standing around shouting instructions than actually producing proteins."

That raised a question of how evolution actually works on the genome, Lander said. With so much of the genome devoted to regulation, it became apparent that evolution could work by simply changing the instructions rather than changing the protein-coding genes themselves.

The opossum genome provided an important point of comparison because it is more distantly related to humans than other mammals whose genomes had been studied. While the common ancestor of humans and opossums split 180 million years ago, the common ancestor of humans and mice split just 80 million years ago.

The research will also prove useful for those seeking to understand opossum biology, according to other researchers involved in the project. Opossums are important models for human disease studies because they're the only animal other than humans who develop melanoma - skin cancer - after exposure to ultraviolet radiation. They are also used in nervous system research because baby opossums can regenerate their spinal cord tissue after it is cut and regain the ability to move their limbs.

[Eric Lander in the Broad Institute is one of the clearest leader in modern Genomics (now "beyond Genes") - Comment by A. Pellionisz, 10th of May, 2007]

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[Los Alamos] Genome Institute Reaches Milestone with a Mighty Microbe [to neutralize Uranium pollution]

Shewanella baltica OS185 is a tiny, ocean-dwelling microbe that could be an answer to cleaning up certain kinds of radioactive contamination, but for a few days this month the microbe is in the spotlight at Los Alamos for another reason. Los Alamos scientists working as part of the Department of Energy's Joint Genome Institute (JGI) recently finished the genetic code of Shewanella baltica OS185 as its 100th genomic sequence.

Finishing a genome is the process of finding and eliminating any gaps in sections of genetic code that were not initially sequenced correctly by automated sequencing methods.

"The finishing of S. baltica is being celebrated as a Los Alamos milestone for a couple reasons," said Chris Detter, leader of the JGI Sequencing Technology Team, "Not only is it our 100th completed genomic sequence, but it's also appropriate because S. baltica has shown potential for use in confining and cleaning up uranium-contaminated areas, such as the Laboratory's legacy waste sites. The microbe might someday be put to work right here at Los Alamos for the bioremediation of uranium contamination at nuclear waste sites because of its unique abilities."

While solid in most forms, uranium can break down over time in the natural environment leading to the possible contamination of groundwater. Taken from the depths of the Baltic Sea, the S. baltica microbe has a unique ability to convert uranium dissolved in groundwater into an insoluble form called uranium dioxide, or uraninite, which prevents the uranium from mixing with water and from migrating into and with groundwater flows.

Los Alamos specializes in developing techniques to take raw sequence data from the high-throughput JGI facility in Walnut Creek, California, and transform it into finished genomes. The Laboratory began finishing sequences for JGI in 2003. Making advancements in genome technology and chemistry over the years, more components of the process have become automated, speeding up finishing rates as a result.

In addition to Detter, other leaders in the JGI-LANL include David Bruce, Tom Brettin, and Cliff Han, and 35 exceptional scientists, technicians, and support staff.

["Defense" and "Environment" are now added to the "Big Pharma" and "Bioenergy" pillars of PostGenetics. Mycoplasma Genitalium, with the smallest genome, is already singled out for H2-based economy. The genome has 8% "junk" (and an identified operon in focus with reversible "on-off" co-action with separate intergenic areas; FractoSets). Mycoplasma Pneumoniae, closely related, works with homologous operon - comparative and evolutionary genomics will yield key (fractal) "genome regulation" insights. Shawanella Baltica has a ten times larger genome, with scores of operons. The race is on, to work out "genome regulation" for the multiple utilizations by "tweaking" DNA of bacteria in major strategic applications - Comment by A. Pellionisz, 8th of May, 2007]

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The Next Human Genome Project: Our Microbes [MetaGenomics and PostGenetics; Common computer algorithms]

George Weinstock, Baylor University, Houston, TX

By Emily Singer
Wednesday, May 02, 2007

A proposed project to sequence the microorganisms that inhabit our bodies could have a huge impact on human health.

Much as we might like to ignore them, microbes have colonized almost every inch of our bodies, living in our mouths, skin, lungs, and gut. Indeed, the human body has 10 times as many [kind of?] microbial cells as human cells. They're a vital part of our health, breaking down otherwise indigestible foods, making essential vitamins, and even shaping our immune system. Recent research suggests that microbes play a role in diseases, such as ulcers, heart disease, and obesity.

While microbes make up such an intimate part of us, most of our microbial inhabitants remain a mystery. The bacteria in the human body are very difficult to study, since only about 1 percent of them can be grown in the lab. Now a proposed new project to sequence all our microbial residents could change that.

"This is completely unexplored territory that is likely to have a large impact on our understanding of human health and disease," says George Weinstock, codirector of the Human Sequencing Center at the Baylor College of Medicine, in Houston. "We hadn't been able to approach it because of the scale of the problem. But now we are finally able to open that door."

Thanks to ever-improving methods to sequence DNA, scientists can now analyze the genomes of entire microbial communities, a field known as metagenomics. By comparing microbial communities in people of different ages, origins, and health statuses, researchers hope to find out precisely how microorganisms prevent or increase risk for certain diseases and whether they can be manipulated to improve health.

Several metagenomics projects are under way or have been completed, including analysis of the microbes living in the human gut and on the skin. But a true snapshot of our microbial menagerie will require a massive effort, along the lines of the Human Genome Project. "Even though a microbial genome is one-thousandth the size of the human genome, the total number of microbial genes in [the human] body is much greater than human genes because you have so many different species," says Weinstock.

The National Institutes of Health (NIH) is now considering such a project. Metagenomics experts and government officials met last week to determine if the proposal, dubbed the human microbiome, will become an NIH "Roadmap" initiative. These NIH-wide programs identify major gaps in biomedical research and provide financial support on a much larger scale than typical grants. A final decision is expected this month.

"At the end of the day, we'll end up with another perspective on the evolution of our species, our human-microbial selves," says Jeffrey Gordon, a microbiologist at the Washington University School of Medicine, in St. Louis.

Recent research from Gordon's lab hints at the potential public-health impact of a clearer understanding of our microbial tenants. Gordon and his colleagues have shown that obese people harbor different microbial communities than lean people. And as obese people lost weight, their microbes began to look more like their lean counterparts' microbes.

Researchers aren't yet sure what triggers the differences, but they found in a similar study in mice that the microbial populations of obese mice could more effectively release calories from food during digestion than could microbes of their lean littermates.

While exciting, Gordon's research also illustrates the challenges of cataloging microbes. To truly interpret the human microbiome, scientists will need to look at the variation in microbial communities among many people and a variety of populations. Complicating the problem is that, while an individual's human genome is static, a person's microbial composition--and thus his or her microbiome--fluctuates over time. So an accurate picture of one person's microbiome could require multiple resequencing efforts.

These types of studies could yield the biggest reward, revealing whether different organisms are correlated with different health states. Gordon and others hope that a microbial analysis will ultimately become a routine part of medical exams, perhaps used to diagnose different diseases.

Scientists are still debating whether the microbiome will become a road-map project, and if so, what the final goals of the project will be: should they focus on generating complete sequences of dominant microbes, for example, or devote equal energy to the complex task of studying microbial variation?

In the meantime, microbiologists are getting ready. Three large sequencing centers--at Baylor, the Broad Institute, and Washington University--have garnered funding to sequence the genomes of a few of the gut microorganisms that can be grown in the lab, which will be crucial in later studies. Ultimately, says Gordon, "we'll get a much more transcendent view of ourselves as a supraorganism with traits acquired from our microbial partnerships."

["Going beyond Genes" required massive computer power coupled with nifty algorithms. Both in PostGenetics (Genomics going beyond Genes) and MetaGenomics (Genomics going beyond a single Genome) the biophysical algorithms will "carry the day" - and the underlying principles of prokaryotic, eukaryotic AND "polykaryotic" organisms (colonies) will have much in common. See comment and diagram from Venter et al. for fractal algorithms as a key to biological constancy AND diversity - Comment by A. Pellionisz, 2nd of May, 2007]

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MicroRNA found in unicellular organism

Yijun Qu, China's National Istitute of Biological Sciences

BEIJING, April 30 (UPI) -- A Chinese-led international team of scientists has, for the first time, identified microRNAs in a unicellular organism.

The team, led by Yijun Qi of China's National Institute of Biological Sciences, made the discovery in green alga Chlamydomonas reinhardtii.

"The finding changes the dogma that miRNAs only exist in multicellular organisms and adds an important piece into the blooming small RNA world," said Qi. "A pressing question we have now is what these miRNAs are exactly doing in the green alga. I hope we will know the answers soon."

The finding shows unicellular miRNAs share functional characteristics with plant miRNAs, in so far as they can direct the cleavage of target mRNAs in vitro and in vivo.

Furthermore, the scientists found miRNA expression patterns changed during gamete differentiation, suggesting a possible role in regulating sexual reproduction.

The discovery also has evolutionary implications, suggesting the miRNA pathway arose before the lineages split. The lack of universally conserved miRNA genes in algae, plants and animals suggests they might have evolved independently.

The research is to appear in the May 15 issue of Genes & Development.

[This news puts not only unicellular organisms (in this case, a plant) on the "map of microRNA" - but further enhances China on the "map of PostGenetics" - Comment by A. Pellionisz, 30th of April, 2007]

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Mouse microRNA knockout uncovers critical roles in immune system

A role for a microRNA in the immune system has been shown by study of one of the world's first microRNA knockout mouse, reported Friday 27 April in Science. The microRNA acts as a lynchpin to balance the response of immune defences and the researchers suggest the corresponding human gene will have a similar vital role.

Cells of the immune system in the knockout mice do not work as well as normal cells and the mice develop symptoms similar to those of human autoimmune disease. They are also less able to resist infection by bacteria, such as Salmonella. The team suggest that the equivalent human microRNA will play a major role in the human immune system.

MicroRNAs are copied from DNA but do not contain code for protein. Rather, they are themselves active in controlling the activity of other genes, often by inducing destruction of protein-coding messenger RNAs or by preventing their activity in the cell.

The research team, led by the Wellcome Trust Sanger Institute, targeted a gene called Bic/microRNA-155 (or miR-155) in embryonic stem cells which they used to transfer the mutation into mice. [Correction for journalists, see bottom: iBic is a gene from which the microRNA-155 is derived from. MicroRNA-s are NOT genes - AJP]. Previous research showed that miR-155 was active in cells of the immune system and overactivity was found in lymphoma development.

"Very little is known about the function of the hundreds of microRNA genes," [genes associated with particular microRNA - AJP] said Dr Antony Rodriguez, lead author on the paper from the Wellcome Trust Sanger Institute. "Although plentiful, this class of genes had never before been knocked out in mice, the best model organism for human disease."

"But we simply did not know whether microRNA knockouts would have an effect in mice: previous knockout studies in nematode worms suggested that most microRNAs were not essential. Our findings were dramatically different."

The effects of the miR-155 knockout swept across the immune system. The team showed that, although knockout of miR-155 did not appear to affect normal growth and development of cells in the immune system, each major cell type - T-cells, B-cells and dendritic cells - performed less well.

"These findings demonstrate the importance of this level of control in the immune system and will lead immunologists to rethink how the immune system works," said Dr Martin Turner, Head of the Laboratory of Lymphocyte Signalling and Development at the Babraham Institute.

The deficits in response were significant: the knockout mice were less able to resist infection by bacteria than mice with normal miR-155, producing lower levels of antibody and a reduced response by T-cells. They also develop changes to lung tissue, with scarring that is similar to some human systemic autoimmune disorders...

"This dramatic finding reflects a large amount of work by collaborating groups," said Professor Allan Bradley, Director of the Wellcome Trust Sanger Institute. "Showing that knocking out a microRNA has such dramatic effects opens new doors to understanding this novel class of gene regulation, with consequences for human health and disease."

"Our work builds upon the sequences of the human and mouse genomes, the power of computer analysis and microarray work and exemplifies why whole-organism research can bring understanding that cannot be developed in any other way."...

MicroRNAs and BIC

MicroRNAs (also known as siRNAs - short, interfering RNAs) are short (22-25 base) sequences that do not code for protein, [that is, MicroRNA-s are "junk" DNA...according to the obsolete terminology - AJP] but can lead to destruction of other RNA molecules or can interfere with their translation. They bind to corresponding bases in the target RNA. The mature microRNAs are derived from larger precursor molecules.

Bic is a non-coding RNA, around 1600 bases in length, which was identified in 1997 as a cancer-causing gene (oncogene) in chickens. The human and mouse versions were discovered in 2001. The BIC gene is activated in cells of the human and mouse immune system and in B-cell lymphomas and some solid tumours.

miR-155 is derived from within the iBic gene and is 65 bases in length: its mature form is 22 bases long. The human equivalent of miR-155 is found on chromosome 21: the mouse and human mature forms of miR-155 differ at one position. To date, some 377 microRNAs have been found in the mouse genome and 474 in the human.

MicroRNAs are being examined as possible therapeutic agents in a range of diseases. Trials are underway for macular degeneration (eye disease), chronic myeloid leukaemia and preeclampsia.

[Stanford] Fire and Mello shared the Nobel Prize for Physiology or Medicine in 2006 for RNAi, which led to discovery of mechanism of action of miRNAs.

[MicroRNA-s are protected intellectual property. Current (average) valuation of a single 21-letter "string" is about $150,000 - but those with direct impact for "Big Pharma" skyrocket; Merck bought SiRNA company for $1.1 Billion - Comment by A. Pellionisz, 28th of April, 2007]

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Japanese Tohoku University International Innovation Forum in Silicon Valley, California

Tohoku University US Office will hold its Opening Ceremony on April 26 and the First Tohoku University International Innovation Forum on April 27 at the Marriott San Mateo at San Francisco Airport , 1770 South Amphlett Boulevard. The US Office is the international promotion center of Tohoku University. The two day event will feature over 50 world renowned experts in their fields speaking on a broad spectrum of science and technology issues to include Nobel Laureate Roger Kornberg, Stanford University Professor, speaking on The Gene Reader in Our Cells. California Governor, the Honorable Arnold Schwarzenegger, is scheduled to present the opening keynote address. The creation of Tohoku’s Silicon Valley California office demonstrates the beginning of its intention to create a portal for the facilitation of collaboration with US companies and educational institutions.

Tohoku US Deputy Director Dr. Toshihiko Nishimura said, “June 2007 will mark the 100th Anniversary of the founding of Tohoku University. It is significant to hold the Opening Ceremony and First International Innovation Forum in the centennial year of 2007. Tohoku University has established unique policies and principles that are “Research First,” “Open Door” and “Practice-Oriented Research and Education.” Our goal for this event is to introduce Tohoku University and showcase its extensive professional and educational achievements, technologies, and intellectual property which are founded on our excellent research and education programs. The goal of the Tohoku University US office is to share and transfer these resources and to contribute to the US industry and society. We want to achieve the position of a world-known university which excels in technology research. We have selected Silicon Valley as the location of our US office, the heartland of technology, from both an academic and commercial perspective.. Our slogan is : Be The Center Of Reference; COR.

More than 50 world renowned experts, in all facets of science and technology including the president, directors, vice directors, deans, and professors from Tohoku University, will attend this event. Delegates from Miyagi Prefecture and Sendai City of Japan and the Federation of Tohoku Economic World will also attend this event. Delegates from the State of California, local counties and cities including government officials and political figures are scheduled to attend this ceremony. Stanford University and University of California will send more than twenty professors to the anniversary ceremony. The Governor of California, the Honorable Arnold Schwarzenegger is scheduled to give a congratulatory speech.

On April 27, Professor Shuji Nakamura, University of California Santa Barbara will open the all-day program of the International Innovation Forum. The 2006 Chemistry Noble Laureate, Roger Kornberg, Stanford University Professor, is the luncheon keynote speaker. Eight sessions are planned for the afternoon. This forum’s philosophy is to introduce Tohoku University’s endeavors to address key current worldwide societal issues in a road show style. Sessions are: environmental issues, energy issues, international pandemic diseases (HIV, Avian Flu), population issues, and issues associated with our aging society.

Tohoku University, being a world leader in the technology fields of Materials Science and Micro Electro Mechanical Systems (MEMS), has created sessions devoted to these topics. The MEMS session will be moderated by world renowned Tohoku University Professor Masayoshi Esashi and will include local Silicon Valley MEMS luminaries including Dr. Kurt Petersen, CEO of SiTime, Roger Howe, Stanford University Professor, Al Pisano, Professor and Director of the University of California Berkeley, Berkeley Sensor and Actuator Center and Masahiko Ogirima, MEMS Core. The Materials Science session will be moderated by Tohoku University Professor Sadamichi Maekawa with panelists including Stuart Parkin of IBM, Robert Sinclair of Stanford University and Masashi Kawasaki of Tohoku University.

Additional sessions include intellectual property collaborations with Tohoku University and future universities collaborations based on the sister city relationship between Riverside and Sendai, Tohoku’s home. At the end of the forum, distinguished US. venture capitalists including Koji Osawa, Co-Founder of Global Catalyst Partners, Steve Domenic, General Partner of Sevin Rosen Funds and James Wei , Co-Founder of Worldview Technology Partners will be joined by Stanford Professor Tom Byers. They will discuss the business vision for universities.

[The RIKEN-based "Genome Network Platform" by Japanese National Institute of Genetics is to help make sure that inside Japan progress keeps abreast with the fierce global competition. Globally, Japan has just established a bridgehead in Silicon Valley, California, with emphatic participation of Stanford and associated Venture Capital groups. Pellionisz, 26th of April, 2007]

[Please welcome the 52nd Founder of IPGS, Dr. Yauchiro Takagi, for his acceptance, keynote lecture and introduction of Nobel Laurate Dr. Kornberg at the 1st Tohoku University International Innovation Forum in Silicon Valley, 27th of April, 2007]

Cure for Alzheimer's: Japanese Vaccine Works On Mice

Reuters; Japan, March 29, 2007

Japanese scientists have developed an oral vaccine for Alzheimer's disease that has proven effective and safe in mice, the director of a research institute behind the project said on Thursday.

The team is preparing to move to small-scale clinical trials in humans, possibly this year, said Takeshi Tabira, director of the National Institute for Longevity Sciences in Aichi, central Japan.

"We hope the Phase I trials go well," Tabira said. "Animals are able to recover their functions after developing symptoms, but humans are less able to do so. It may be that this only works in the early stages of the disease, when symptoms are light."

When administered to mice suffering from the disease, which causes dementia and is currently incurable, the vaccine reduced the amount of amyloid plaques in the brain and improved mental function.

Amyloid plaques are believed to be at the root of Alzheimer's -- a growing problem for ageing populations around the world. The disease affects five million in the United States alone, the Alzheimer's Association said in a report last week.

The treatment did not cause inflammation or bleeding in the brains of the mice, Tabira said. The vaccine is made by inserting amyloid-producing genes into a non-harmful virus. When taken orally, the virus stimulates the immune system to attack and break down the amyloid proteins in the brain, Tabira said.

The treatment was tested on 28 mice genetically modified to develop Alzheimer's disease. Half the animals were given a dose of the vaccine at the age of 10 months, while the control group were not treated.

Three months later, tests showed mental function in the treated mice had returned to levels close to those before they developed Alzheimer's symptoms.

U.S. drugmaker Wyeth and its Irish partner Elan Corp have an Alzheimer's vaccine called ACC-001 in early stage human trials.

The Japanese research, carried out in conjunction with scientists at Nagoya University and others, is to be published by the Federation of American Societies for Experimental Biology in July.

[Alzheimer's appears to be one of the so many genome-regulation ("junk" DNA) diseases) - but even before genome-regulation is fully understood (and accordingly, root-cause therapy would be possible), some regulatory diseases where metabolic agents are excessive or insufficient, apparently could be treated by supplanting missing agents (occasionally as simple as Vitamin D) - or as in this case developing vaccines to use the immune system to fight a misregulated and excessive amyloid protein production. Another significant aspect of the news is, that Japan, with its high respect and devotion to the aging population focuses on innovative therapy of "regulatory DNA diseases", such as Alzheimer's. In the PostModern age of "Genomics beyond Genes" Japan is to be watched - A. Pellionisz, 26th of April, 2007]

[Eric Mathur] named vice president of the J. Craig Venter Co. [La Jolla]
04/16/2007

Eric Mathur of Carlsbad, ... was recently appointed vice president of the J. Craig Venter Co. in La Jolla, the discoverer of the human genes sequence...

He has been a research scientist at UCR, the Scripps Institute, Stratagene Cloning System Inc. and the Diversa Corporation (as co-founder) and recently was distinguished scientific consultant and research fellow at the J. Craig Venter Institute and its Synthetic Geonomics Inc.

Most of his activities have been and are in the field of rapidly advancing genetic engineering and sciences boundaries.

He has published more than 60 scientific papers, and is named inventor on more than 50 issued U.S. and world patents, and has been invited to present more than 100 scientific lectures.

Mathur's parents immigrated to the United States in the 1940s and 1950s. His mother, a retired Redlands teacher, came from Latvia, and his father, who was a defense research and development engineer with Aerospace Corp. and TRW, came from India.

[A genuine entrepreneur who not only understands but makes the academia-industry "tech transfer" work will do wonders to the "for profit wing" of "Venter Ventures" in California. An especially challenging task is, beyond catalogueing phylogeny, to pinpoint by powerful computer algorithms the "hot spots" from fragments (of "fractals"...) where the needles might lie in the haystack of the myriads of diversed species. Another key issue might be to spot genome regulation wherever it is conspicuous and translate the understanding into genome regulation modification, e.g. for bioenergy and postgenetic new materials - A. Pellionisz, 26th of April, 2007]


'Junk' DNA now looks like powerful regulator, Stanford researcher finds

Craig Lowe (UCSC)

STANFORD, Calif. -- Large swaths of garbled human DNA once dismissed as junk appear to contain some valuable sections, according to a new study by researchers at the Stanford University School of Medicine and the University of California-Santa Cruz. The scientists propose that this redeemed DNA plays a role in controlling when genes turn on and off.

Gill Bejerano, PhD, assistant professor of developmental biology and of computer science at Stanford, found more than 10,000 nearly identical genetic snippets dotting the human chromosomes. Many of those snippets were located in gene-free chromosomal expanses once described by geneticists as "gene deserts." These sections are, in fact, so clogged with useful DNA bits - including the ones Bejerano and his colleagues describe - that they've been renamed "regulatory jungles."

"It's funny how quickly the field is now evolving," Bejerano said. His work picking out these snippets and describing why they might exist will be published in the April 23 advance online issue of the Proceedings of the National Academy of Sciences.

It turns out that most of the segments described in the research paper cluster near genes that play a carefully orchestrated role during an animal's first few weeks after conception. [See the "Methylation prediction of FractoGene" - AJP]. Bejerano and his colleagues think that these sequences help in the intricate choreography of when and where those genes flip on as the animal lays out its body plan. [The vague notion of gene "turn on" is a "turn off" for theorists. No serious computer scientists would ever describe the role of software "to turn bits on and off" in a computer. "Intricate choreography" is better journalism, but still no substitute for hierarchical (recursive) protein synthesis where the fractality of organism is governed by the fractality of DNA - AJP]In particular, the group found the sequences to be especially abundant near genes that help cells stick together. These genes play a crucial role early in an animal's life, helping cells migrate to the correct location or form into organs and tissues of the correct shape.

The 10,402 sequences studied by Bejerano, along with David Haussler, PhD, professor of biomolecular engineering at UC-Santa Cruz, are remnants of unusual DNA pieces called transposons that duplicate themselves and hop around the genome. "We used to think they were mostly messing things up. Here is a case where they are actually useful," Bejerano said.

He suspects that when a transposon is plopped down in a region where it wasn't needed, it slowly accumulated mutations until it no longer resembled its original sequence. The genome is littered with these decaying transposons. When a transposon dropped into a location where it was useful, however, it held on to much of the original sequence, making it possible for Bejerano to pick out.

In past work, Bejerano and his co-workers had identified a handful of transposons that seemed to regulate nearby genes. However, it wasn't clear how common the phenomenon might be. "Now we've shown that transposons may be a major vehicle for evolutionary novelty," he said.

The paper's first author, Craig Lowe, a graduate student in Haussler's lab at UC-Santa Cruz, said finding the transposons was just the first step. "Now we are trying to nail down exactly what the elements are doing," he said.

Bejerano's work wouldn't have been possible without two things that became available over the past few years: the complete gene sequence of many vertebrate species, and fast computers running sophisticated new genetic analysis software. "Right now it's like being a kid in a candy warehouse," Bejerano said. Computer-savvy biologists have the tools to ask questions about how genes and chromosomes evolve and change, questions that just a few years ago were unanswerable. [Correction: they could have been answerable e.g. for human and mouse genomes since 2002 but considering 98.7% "Junk" there was no money to run with suitable software built for computers that did exist. Now even NIH - and EU - start pouring money, but private business will run away with the fat profits just as GenenTech did when "genes" became technologically approachable - AJP]

Bejerano and his colleagues aren't the first to suggest that transposons play a role in regulating nearby genes. In fact, Nobel laureate Barbara McClintock, PhD, who first discovered transposons, proposed in 1956 that they could help determine the timing for when nearby genes turn on and off.

[Neither the repetitive self-similarity in heredity is new (Darwin 1859, pp. 477), nor is "regulation" in the genome (in addition to McClintock, 1956 see also the "Operon"-regulation by François Jacob and Jacques Monod, as early as 1961, Nobel in 1965). The challenge in our times is not so much "to open the pandorra box of regulatory data" (that is "only" a function of funds), but to consolidate them into an understanding that helps hundreds of millions of "junk DNA disease" patients, while turns a profit of doing so. "Big science" will not rush for understanding at all (the more heterogeneous the body of data is the more people can draw funds to make it even more diverse). However, patients and consumers will screem for help - and the industrial wing of PostGenetics (with "Big pharma" and "Bioenergy" in the lead) will deliver in spades - A. Pellionisz, 23th of April, 2007]



Could US scientists get EU funding?

European Medical Research Councils to discuss allowing US citizens to apply for grants
By Stephen Pincock
[Published 19th April 2007 01:23 PM GMT]

Representatives of Europe's national medical research councils are planning to discuss next week the possibility of letting US scientists apply for European research funding, in the same way that European researchers can receive funding from the US National Institutes of Health.

Liselotte Højgaard, chair of the standing committee of the European Medical Research Councils (EMRC) told The Scientist that during the organization's annual meeting in Stockholm next week, members would discuss a potential white paper on clinical trials in Europe.

One item that might make it into that white paper is the idea of levelling the playing field for US researchers in terms of EU funding, she said. "In my personal opinion the current situation is utterly unfair. I know that I have personally applied for NIH funding [in the past] and have really appreciated it."

Under current arrangements, researchers from outside the US can apply for NIH funding. The NIH website lists 188 grants made in 2007 to researchers based outside of the US, some for close to $1 million.

Researchers based outside of Europe, however, cannot apply for EU funding. At the newly established European Research Council, for example, "funds are open to any scientists (of any nationality) based in the EU," European Commission spokesperson Antonia Mochan said in an Email.

Højgaard, head of the department of clinical physiology and nuclear medicine at Rigshospitalet, Copenhagen University Hospital, was careful to say she couldn't predict the outcome of the debate, which would involve representatives from agencies such as the UK's Medical Research Council, the Deutsche Forschungsgemeinschaft (DFG) in Germany, and INSERM in France among others.

"It's only one small item on a long agenda," she said. "I will ask my fellow medical research council representatives whether it is of their concern also." Denmark is already discussing changing its national law to allow people from outside Europe to apply for research grants, she said.

The Scientist contacted the British, French and German medical research councils for comment. Mark Palmer from the UK's MRC declined to comment until the issue had been discussed by the board; representatives of INSERM and DFG did not return calls by deadline.

Mochan said that EU research commissioner Janez Potocnik and NIH director Elias Zerhouni had discussed the matter informally, but that the European Commission had nothing further to add at this time.

The EMRC was established in 1971. Part of its role is to develop European scientific strategies and stimulate collaboration in emerging and interdisciplinary research areas.

Stephen Pincock

[It is not only a good idea for US researchers to compete for EU research funds ("levelling the field of global competition" in order to break down monopolies of "science establishments"), but it is a formal recognition of the already existing fact that "brain drain" is not as "one-sided" as it used to be. Just as Liselotte Hojgaard quoted her personal case (having applied for US funds from EU), this columnist could quote episodes from his experience, from a complementary viewpoint. Germany has long established the "Senior Distinguished American Scientist Award", in recognition of the US "Marshall Plan" and NASA's application of a paradigm-shift of Neural Networks was quickly followed by awarding the "Alexander von Humboldt Prize" (on German money) to AJP. Likewise, very recently, the "European Inaugural of International PostGenetics Society" in Hungary resulted in awarding to AJP an "European Union Visiting Professorship" - since small new member countries of the EU are unlikely to be able to compete in "Modern Genetics" with established giants such as the UK, Germany, The Netherlands, etc. thus the newly ascended member countries of the EU would like to directly plunge into the "PostModern era of Genetics" (PostGenetics). However, given their meager resources and formidable transitional challenges, they need their US-based researchers to "pitch in" with the EU for the accomplishment of full collective success in PostGenetics. This is quite similar to global cooperation in stem cell research, where notable US-based researches turned to their UK roots to accomplish difficult goals of a paradigm-shift. - A. Pellionisz, 21th of April, 2007]

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MicroRNAs Debut [at NIH] as Key Actors in Health and Disease

Genomeweb: NIH Awards Five Grants in March, April To Support microRNA-Related Research
[April 12, 2007]
By Doug Macron

The grants, worth a combined $992,000 in their first years, reflect the rapidly growing interest in microRNAs as key players in pancreatic development, cognition and behavior, aging, and small-molecule and protein-synthesis inhibition.

One of the dogmas of biology has been that proteins, the cellular workhorses of our bodies, perform the critical job of controlling gene activity. But a series of recent discoveries is painting a strikingly different picture.

A newly identified kind of RNA, called microRNA for its tiny size, appears to control a third of our genes. Scientists are finding that microRNAs play starring roles in a remarkably wide range of biological processes.

Two studies in 2005 implicate microRNAs in cancer. Using microscopic roundworms, Frank Slack, Ph.D., of Yale University in New Haven, Connecticut, discovered that one particular microRNA can quiet Ras, a protein known to be central to tumor formation when it is mutated. In a separate study, Gregory Hannon, Ph.D., of Cold Spring Harbor Laboratory in New York identified other microRNAs linked to the severity of B-cell lymphoma in mice. These findings open promising new avenues for preventing, diagnosing, and treating cancer.

In a third study, Richard Carthew, Ph.D., of Northwestern University in Evanston, Illinois, and Hannele Ruohola-Baker, Ph.D., of the University of Washington in Seattle uncovered telltale signs of microRNA involvement in stem cell growth. Unlike most cells, stem cells have the ability to continuously renew themselves, yet scientists do not understand how this happens. The new research, done in fruit flies, revealed that stem cells need certain microRNAs to maintain their ability to divide endlessly.

Research on microRNA is still in the early stages, but the recent discoveries linking microRNAs with cancer and stem cell biology are fueling excitement about the potential therapeutic uses of these multitalented molecules

[This is a singularity in the history of sciences. While some quarterbacks are still clinging to the "Junk" DNA misnomer, non-coding parts of the genome (e.g. microRNA-s) are fervently picked up both by "Big Pharma" (see Merck's buying SiRNA for $1.1 Billion), are revolutionizing PostModern Medicine (e.g. in cancer and stem cell research & therapy), and regulation is emerging as a key issue in Bioenergy (e.g. in synthetic genomics tweaking DNA to produce a H2 economy). Formal abandonement of the "Junk" DNA misnomer does not count nearly as much as the $1 Million support by NIH of just one segment of PostGenetics; experimental microRNA research. The big question is how private industry will catapult on these disruptive developments - A. Pellionisz, 21th of April, 2007]

Genomicists Tackle the Primate Tree

Science, Apr. 13.
Elizabeth Pennisi

Richard Gibbs, Baylor, Houston, Texas

Primates are taking center stage in genomics, with the macaque serving as an early milestone in understanding our relatives' genomes--and therefore our own

The deciphering of the human genome was a humbling experience. The promise of the project, in the words of James Watson, was "to find out what being human is." But even when most of the 3 billion bases of the human genome had been properly placed, much about the sequence defied understanding. Where in the 20,000 human genes uncovered are the ones that set Homo sapiens apart from other mammals, or other primates? To find out, genomicists have been scrambling for more data [in the sciences "data" are the sine qua non" - but without theory, data alone never yield understanding - AJP] ever since, most recently from primates. "The goal is to reconstruct the history of every gene in the human genome," [is it, really? - should it not be an understanding why some human genes may not have a "history" - AJP] says Evan Eichler, a geneticist at the University of Washington, Seattle. And that requires data from our relatives. DNA from different branches of the primate tree will allow us "to trace back the evolutionary changes that occurred at various time points, leading from the common ancestors of the primate clade to Homo sapiens," says Bruce Lahn, a human geneticist at the University of Chicago in Illinois.

In 2005, the unraveling of the chimp genome provided tantalizing hints about differences between us and our closest relative (Science, 2 September 2005, p. 1468). Now ... the third primate genome, that of the rhesus macaque, begins to put the chimp and human genomes into perspective. Macaques are Old World monkeys, which split perhaps 25 million years ago from the ape lineage that led to both chimpanzees and humans.... So when compared to apes, monkeys can help identify the more primitive genetic variants, allowing researchers to tease out the changes that evolved only in apes. Researchers want to take such analyses back to even more ancient evolutionary divergences, and so seven more primate genome sequences are under way, as is the sequencing of the DNA of two close nonprimate relatives. Together, these genomes "should teach us general principles of primate evolution," says Lahn. [They "should" but don't be surprised if "comparative genomics" may not yield clues unless and until we define *what* we are "comparing" - AJP]

A consortium of more than 100 researchers who have been unraveling the macaque genome are detecting genes that have changed faster than expected in the chimp and human lineages; such speed is usually a telltale sign of significance in evolution. They are also finding that dozens of base changes known to put humans at risk for disease also exist in the healthy macaque--but not in the chimpanzee. That suggests that some gene variants implicated in disease are relics of the ancestral primate condition. Such studies "may be the bridge between comparative genomics and evolutionary biology," says Richard Gibbs, director of the Baylor College of Medicine Human Genome Sequencing Center in Houston, Texas, and coordinator of the rhesus macaque genome project. [Here you go! There is a specific theoretical hypothesis lurking here; that the emergence of species is hierarchical, and a lapse back into an "outgrown" phase is not only "obsolete" but may be a harmful "glitch" - AJP]

Gibbs and his colleagues are tackling evolutionary biology in reverse. They are identifying key genomic differences without yet knowing how or whether those differences translate into traits that provide survival advantages. Traditionally, researchers have first traced changes in the shapes and sizes of beaks, bodies, brains, and so on, then sought the genes behind them. The hope is that the two modes of inquiry will meet in the middle. But so far researchers have come up short in linking genomic changes to traits subjected to natural selection and other evolutionary forces, ironically because of sparse biological data on nonhuman primates, says glycobiologist Ajit Varki of the University of California, San Diego: "[Without] basic information about the chimp, its physiology, its diseases, its anatomy, you are really very impoverished about what you can say."

Beyond mouse

In 2001, the human genome sequence drove home how little we knew about our genomic selves. About one-third of our genes were complete unknowns. Researchers immediately started lining up our DNA with that of worms, fish, and rodents to see what genes matched up and to try to pin down functions. They found not just genes but also conserved regions within the "junk" DNA that played as critical a role in genome function as the genes themselves. Their finds led to an unquenchable thirst for sequence data as a way to clarify how genomes work. "Every additional species increases our ability to resolve functional from nonfunctional [DNA]," explains Ross Hardison, a molecular biologist at Pennsylvania State University in State College.

The surprise of the chimp genome, the first nonhuman primate to be sequenced, was the large number of insertions and deletions that differed between humans and our closest living cousins. There were more changes in the order and number of genes and blocks of genes than changes in single base pairs, highlighting the importance of this kind of expansion and shuffling in primate speciation.

But the chimp data proved frustrating as well, because researchers couldn't put the chimp-human comparisons into an evolutionary context. If humans had one base, say a C, at a position where chimpanzees had a G, researchers had no way of knowing which base represented the ancestral condition. [It is much worse, since we can not exclude the theoretical possibility that "neither" - AJP]. Consequently, there was no way to tell whether the change at that position had occurred only in humans--and therefore perhaps helped define Homo sapiens--or in the chimp. And so in 2005, the National Human Genome Research Institute began stuffing more primates into the sequencing pipeline and approved the $20 million rhesus macaque sequencing project. "It is great to finally have a [distant relative] that allows us to assign differences between the human and chimpanzee genomes to either the human or the chimpanzee evolutionary lineage," says Svante Pääbo of the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany.

Sequencers aren't stopping at the macaque. Sequencing of many primates, including the orangutan, the gibbon, and a New World monkey, the marmoset, is under way, with promises that the baboon should be next. In 2006, the Wellcome Trust Sanger Institute in Hinxton, U.K., started deciphering the gorilla genome, planning coverage similar to that of the macaque. Meanwhile, genomicists have started sequencing key genes and regulatory regions from other primates, too. "To tell what is human-specific, you need this comparative context," says Anne D. Yoder, an evolutionary biologist at the Duke Lemur Center in Durham, North Carolina[When is "enough" "enough"? Never. Venter has just collected (and is sequencing) gezillions of genomes - leading to not only "comparative genomics" but "metagenomics". Even with sequencing getting increasingly dramatically less expensive - the amount of resources going into "data collection" is certainly in the range of hundreds of millions of dollars - while the theorethical efforts, e.g. those advocated by PostGenetics are disproportionally neglected. Trends of sciences suggest that - just as in nuclear physics - quickest advances will occur where data-production (e.g. by smashing nuclear particles) will be at least accompanied, but preferably guided by, quantitative theoretical predictions that are testable by experimentation - AJP]

To know a genome

Already, the primate genomic data are revealing bits of our genetic history. For example, more than 98% of chimp and human bases agree. So researchers hoping to pick out areas with fewer base changes than expected--such as regulatory regions conserved in all apes--are awash in a tide of virtually identical DNA. But when the search is expanded to additional primates, there's more variation in the sequences, and previously undetectable conserved regions, even small regulatory sequences, begin to surface.

For example, Dario Boffelli, now at Children's Hospital Research Center in Oakland, California, and his colleagues at the Joint Genome Institute in Walnut Creek, California, wanted to understand the regulation of genes that help maintain healthy levels of cholesterol in the body. They looked at 558,000 bases covering genes involved in cholesterol processing, comparing human and six other primates: baboon, colobus monkey, dusky titi, marmoset, owl monkey, and squirrel monkey. They discovered regions with virtually the same sequence in all the primates. Subsequent experiments showed that three of the newly identified conserved regions do indeed regulate genes in the cholesterol pathway, Boffelli's team reported in January in Genome Biology.

In other cases, particularly as researchers look for differences that reflect independent evolution, data from even one additional primate can help. In one analysis, the macaque team looked at 64,000 places in the macaque genome where they knew a disease-related mutation existed. In the past, researchers have assumed that such mutations were specific to humans. A few chimp genes had hinted that some problematic bases might predate humans, but the macaque drives home how often this may be the case. Hardison and his Pennsylvania State colleague Webb Miller found more than 200 sites where the macaque had the same base at the same position as the diseased or at-risk human. In 97 instances, both the chimp and the macaque matched the aberrant human base; in 48 cases it was just the chimp. And in 84 cases the rhesus, but not the chimp, matched the diseased human sequence, possibly because chimps also independently evolved away from the ancestral condition at those sites.

For example, about 1 in 15,000 people have phenylketonuria because their gene for an enzyme needed to process the amino acid phenylalanine is defective. Untreated, the buildup of a toxic byproduct causes mental retardation. In macaques, that same defective gene is the normal condition and has no ill effects. It could be that many "disease" variants in humans are simply ancestral variants "where [a dietary or environmental] change between the human ancestor and the human has made a variant that used to be good, bad," says Miller.

In addition, the macaque genome consortium combed the macaque, chimp, and human genomes for families of genes that had expanded in one or more species. A family consists of the original gene and any subsequent copies, many of which evolve slightly different sequences and functions over time.

One in particular intrigued Miller. This family, called PRAME--short for "preferentially expressed antigen of melanoma" because the genes are activated in melanoma and other types of tumors--has had a complex history in humans. It has at least 26 intact members on chromosome 1. It's one of the regions of the human genome that "are going wild," says Miller. The chimp has a similarly complex set of PRAME genes, but Miller found just eight PRAME genes in the macaque. "The cluster is very simple [and has] remained stable for millions of years," he explains. Working from this simpler, presumably ancestral set, he and his colleagues hope to unravel the timing and types of duplications that resulted in the abundance of human PRAME genes.

Elsewhere in the genome, the consortium found that the macaque has as many as 33 major histocompatibility complex (HLA) genes, more than triple the number in humans. "When you see a dramatic change, it suggests there was some evolutionary selection that favored those extra copies," says James Sikela, a computational biologist at the University of Colorado Health Sciences Center in Denver. "The tough question is, 'What favored that event?' "

While Sikela and colleagues ponder the macaque's need for HLA genes, Adam Siepel of Cornell University and his collaborators found other genes in which mutations were apparently favored by selection. Such positive selection, as it is called, typically shows up as bases that have mutated faster than would occur by chance. So Siepel's team compared 10,376 macaque genes with their equivalents in both the chimp and human genomes. They sought genes with a relative mutation rate that was higher in bases that changed the encoded amino acid than in bases that did not alter the coding. The researchers found 178 such genes, "considerably more" than previously identified in human-chimp scans, says Siepel. Some genes, such as a few involved in the formation of hair shafts, were changing rapidly in the three species, possibly because climate change or mate-selection strategies spurred rapid evolution, Siepel speculates.

Other positively selected genes detected in at least one species included those involved in cell adhesion and cell signaling, as well as genes coding for membrane proteins. "We don't really know enough at this stage to point to a case where we have a really nice story of a difference at the molecular level that we can connect to a known phenotypic difference," Siepel laments.

Siepel and others say that such stories require more primate sequences. Evidence of positive selection in the same genes in multiple species will provide more clues to what prompted such rapid evolution. Moreover, researchers can be more confident about labeling a gene as "human-specific" once they have looked in a number of our relatives and not found it. "The more primates one can compare, the better," says Sikela.

Sequencing decisions require tough choices about what species to sequence and how thoroughly, however. For his part, Boffelli thinks seven or eight primates would suffice and favors apes over prosimians, the most primitive living primates. With ape DNA, it will be easier to look for positive selection that led to humans. But Yoder thinks it's also important to understand how the whole primate branch has evolved, a point long made by researchers studying anatomy and behavior. "If you are going to understand which genes are primate-specific, you need a pretty broad phylogenetic spectrum, [with] things outside the primate clade but close to it," she notes. That argument has already brought tree shrews and flying lemurs (which are not lemurs at all) into the picture, with researchers planning a quick skim across the DNA to get a very rough draft sequence.

Others warn that the quick skim, which is also planned for the bushbaby, mouse lemur, and tarsier, might not be enough, however. With anything short of finished sequence, the computer programs may pick up differences--signs of evolution--that in reality may be sequencing errors, warns Miller. That was the lesson of the chimp genome, which initially was not a very polished draft.

Varki says the genomic work promises to be challenging in other ways, too: "At the genomic level, evolution is extremely messy, involving every conceivable mechanism, probably with lots of blind alleys and red herrings. Deciphering the significance of these molecular changes will be far, far more complicated than I imagined." ...

[Comparative Genomics and Evolutionary Genomics, as Gibbs points out, will eventually be reconciled. With the help of Theoretical PostGenetics, one might add - since it is already evident that it is more useful to analyse (and interpret) what is *the same* (conserved) in the genome of different organisms, rather than pretend to know what deviations may mean. The "evolutionary tree" (e.g. a "primate tree") - similarly to "regular trees" are highly efficiently modeled as "fractal trees".

PLOS 2007, (5)3 pp. 0447

The Phylogenetic tree of Prokaryotes (of just 50 or so bacteria...) has already been modeled as a multifractal (Zhou-Guo Yu, 2004). There is good reason, at least at the level of a hypothesis to look at Venter's Metagenomics (see their Fig. above) leading to fractal geometry that unites Comparative Genomics, Evolutionary Genomics into PostDarwinism. PostGenetics ("Genomics beyond genes" will help in this process, since Darwin [1859] not only could not be aware of "Genes" meant in the sense of "Classical Genetics"[Bateson, 1905], but "ultraconserved elements" and conserved regulatory sequences across species emerged only lately when Genomics started to look collectively, in earnest "beyond Genes"). The PostModern era of Genetics, "PostGenetics" itself has not existed as a field until a Century after Bateson (2005) - with the formal abandonment of "Junk DNA" misnomer by IPGS (2006)- A. Pellionisz, 14th of April, 2007]

J. Craig Venter Institute Announces Management Team and Organizational Structure

J. Craig Venter, Ph.D., Founder, remains as President and Chairman;
Robert Strausberg, Ph.D., is named Institute Deputy Director

ROCKVILLE, MD—April 11 , 2007—The J. Craig Venter Institute (JCVI), formed in October 2006 through the merger of several affiliated organizations—The Institute for Genomic Research (TIGR), The Center for the Advancement of Genomics (TCAG), and the J. Craig Venter Science Foundation (JCVSF), today announced the new management team and organizational structure for the JCVI.

J. Craig Venter, Ph.D., founder, remains as Chairman and President of the new JCVI. Robert Strausberg, Ph.D., who had been president of the TCAG division, is now the Deputy Director. Marv Frazier, Ph.D., former Vice President for Research at TCAG is now the Executive Vice President for Research. The General Counsel for the JCVI is Julie Gross Adelson; Chief Financial Officer is Aimee Turner, who was formerly CFO at TIGR; Vice President of Human Resources is Robin Hoesch and Robert Friedman remains as Vice President for Public Policy.

The Institute will no longer be organized under the two research divisions TIGR and TCAG, but will now encompass an administrative team and the following research groups: Genomic Medicine, Infectious Disease, Synthetic Biology & Bioenergy, Plant Genomics, Microbial & Environmental Genomics, Pathogen Functional Genomics Resource Center (PFGRC), Applied Bioinformatics, Research Informatics, Software Engineering, and the Policy Center. The genomic sequencing capability remains a cornerstone of activities at the JCVI and will continue to be led by Yu-Hui Rogers. Eric Eisenstadt, former Vice President for Research of TIGR is the new Deputy Vice President for Research.

With six buildings and more than 250,000 square feet of lab space in Rockville, MD, as well as a research facility in La Jolla, CA, and combined assets of more than $200 million, JCVI is one of the largest independent research institutes in the Unites States. There are approximately 500 employees, of whom nearly 400 are dedicated to research with 124 of those having doctoral degrees. The organization also boasts one Nobel Laureate and three members of the National Academy of Sciences.

“Since the earliest days of founding TIGR in 1992 and then with the other affiliated institutes, my goal has always been to create unique and dynamic research organizations that push the boundaries of traditional science. We have long been leaders in genomics and with our newly organized Institute, I am certain we are poised to continue to blaze new trails in this field,” said Dr. Venter.

About the J. Craig Venter Institute

The J. Craig Venter Institute is a not-for-profit research institute dedicated to the advancement of the science of genomics; the understanding of its implications for society; and communication of those results to the scientific community, the public, and policymakers. Founded by J. Craig Venter, Ph.D., the JCVI is home to approximately 500 scientists and staff with expertise in human and evolutionary biology, genetics, bioinformatics/informatics, information technology, high-throughput DNA sequencing, genomic and environmental policy research, and public education in science and science policy. The legacy organizations of the JCVI are: The Institute for Genomic Research (TIGR), The Center for the Advancement of Genomics (TCAG), the Institute for Biological Energy Alternatives (IBEA), the Joint Technology Center (JTC), and the J. Craig Venter Science Foundation. The JCVI is a 501 (c)(3) organization. For additional information, please visit http://www.JCVI.org.

The University of Maryland School of Medicine in Baltimore has named preeminent genome scientist and microbiologist Claire M. Fraser-Liggett, PhD, to head the University of Maryland School of Medicine's Institute of Genome Sciences - a new research enterprise dedicated to the application of genome sciences for the advancement of human health. This new institute will be located at the University of Maryland, Baltimore (UMB) BioPark, a biomedical research park on UMB's expanding campus.

Fraser-Liggett comes to the School of Medicine from The Institute for Genomic Research (TIGR) in Rockville, MD, where she has served as president and director since 1998. During her tenure at TIGR, federal funding to the organization tripled to $60 million per year. At TIGR, Fraser-Liggett led research teams that sequenced the genomes of many microbial organisms and helped to initiate the era of comparative genomics. She has been the most highly cited scientist in the field of microbiology for the past 10 years.

"Dr. Fraser-Liggett is a true pioneer in the effort to sequence and analyze the genomes of a large number of organisms, and we are thrilled to have her world-class expertise at the University of Maryland," says E. Albert Reece, MD, PhD, MBA, vice president for medical affairs and dean of the School of Medicine. "Dr. Fraser-Liggett is expected to bring a team of scientists and staff members with her. This major recruitment initiative will fuel the expansion of genomic research at the School of Medicine."

As an expert in the field of microbial genomics, one aspect of Fraser-Liggett's current research is to understand the communities of bacteria in the human body, especially the microorganisms that reside in the digestive tract. These bacterial cells far outnumber the human cells that make up our bodies and are vital to good health.

By comparing DNA sequences from these microbes, researchers have already determined the biological function of some beneficial bacteria. The research could lead to new ways to promote health and novel vaccines to prevent disease.

"I am extremely excited about the opportunity to build a new genomics institute within the School of Medicine," says Fraser-Liggett. "The School of Medicine has a rich history in medical and graduate education and an outstanding faculty in both basic and clinical research, many of whom are current or past collaborators with TIGR."

Fraser-Liggett has overseen the genome sequencing of important human pathogens, including bacterial infections that cause cholera and anthrax, and parasitic infections responsible for malaria and other devastating diseases in the developing world. Her work also includes the study of influenza and other viruses. These studies have provided a strong foundation for the development of new diagnostics, therapeutics and vaccines.

At the University of Maryland, Fraser-Liggett will build on her impressive body of work while collaborating with physician-scientists in an environment that fosters translational medicine.

"One of the most important challenges over the next two decades will be integrating new insights from the past 10 years of genomics studies into the clinical environment to impact human health," says Fraser-Liggett. "There is no better place to be working toward these goals than in a large academic medical center like the University of Maryland School of Medicine."

"The University of Maryland School of Medicine's Institute of Genome Sciences will provide countless opportunities for multi-disciplinary collaboration," says Bruce E. Jarrell, MD, vice dean for research and academic affairs. "Institute faculty will have opportunities for clinical research and benefit from the School of Medicine's strong international programs, such as the Center for Vaccine Development, headed by Dr. Myron Levine; the Institute of Human Virology, led by Dr. Robert Gallo; and the Department of Microbiology and Immunology, chaired by Dr. James Kaper."

Fraser-Liggett has been continuously supported by federal funding, including the National Institutes of Health). She currently serves on the National Science Advisory Board for Biosecurity and the National Research Council's Committee on Metagenomics. She is a member of the editorial boards of The Journal of Biological Chemistry and The Journal of Bacteriology. She has published more than 220 articles in scientific journals and is a reviewer for nine journals.

["Boom" is defined by multiple bidders competing for the same resources - A. Pellionisz, 12th of April, 2007]

Scientists reveal structure of gateways to gene control

Scientists at Penn State University will reveal in the 29 March 2007 issue of the journal Nature the first complete high-resolution map of important structures that control how genes are packaged and regulated throughout an entire genome. "For the first time, we are seeing in very high resolution on a genome-wide scale how nucleosomes control the expression of an organism's genes," said B. Franklin Pugh, professor of biochemistry and molecular biology and the study's lead investigator.

The map pinpoints the locations of certain key gene-controlling nucleosomes -- spool-like structures that wrap short regions of DNA around a protein core. The research suggests how these nucleosomes, positioned at important transcription-promoter sites throughout the cell's DNA, control whether or not a gene's function can be turned on in a particular cell...

The study revealed that almost all genes have the same kind of structure where transcription begins, that this beginning contains a critical gateway for transcription, and that the transcription gateway of each gene almost always is located at the same place on a nucleosome. The researchers also discovered some genes whose pattern is somewhat different from this norm, and these unusual sequences also are reported in the Nature paper. "We previously had a low-resolution idea that these structures all could be roughly in the same position, but now this high-resolution map makes it very clear that they really are in exactly the same position. It's a remarkably consistent arrangement," Pugh said.

The study also revealed that the nucleosomes at the transcription-promoter control centers occupy several overlapping positions on the DNA molecule, typically 10 base pairs apart, which exactly matches the periodic rotation of the DNA double helix. "It is striking how well these positions match with the architecture of the DNA as it wraps around the nucleosome's protein core," Pugh said.

This result powerfully simplifies previous theories about the possible architecture of gene packaging. "There is a certain DNA sequence that shapes the gene's architecture in the same way, producing the same structure in every gene," Pugh said. The overall sequence of DNA building blocks is different in each gene, but the underlying architecture is the same."...

Another discovery is that transcription-control centers tend to be located on the outside edge of the nucleosome and tend to face outward on the DNA helix, allowing the cell's transcription proteins to find them more easily. "This arrangement makes sense, because when signaling proteins arrive at a control center they are well situated to help push the nucleosome out of the way so the reading of the gene can begin," Pugh said.

"Previous research had indicated that DNA sequences located upstream of a gene might be a region that controls whether that gene is read or not, but we did not know the architecture of those sequences -- whether they were exposed and therefore ready for work. Now we know that the gateway to transcription is a part of this control region and that the nucleosome keeps it locked so the gene cannot be turned on until it is needed," Pugh said. When the gene is needed, the cell's molecular machinery loosens the DNA wrapping around the nucleosome, unlocking the transcription gateway to give access to the cell's molecular transcription machinery. "We think that the function of the nucleosome is to control the gateway to transcription," Pugh said....

The knowledge that most genes are packaged basically the same way is powerful information with implications for future research and potential applications. "One implication that I think is important is that we now have a better idea about how packaging the DNA in nucleosomes controls the expression of a gene," Pugh said. "We don't yet know where all the important gene-regulation features are located on the DNA molecule, but now we know we should start looking for some of them on the edges of nucleosomes," Pugh said. "We might even discover some sites that regulate genes that we didn't even know existed."

[Histone-nucleosome regulation has been featured in this column. With the results becoming ever more convincing, the key question is starting to emerge how the "signalling proteins" unlock one packet of DNA information after another in a hierarchical manner, to give rise to a recursive iterative (fractal) protein synthesis - A. Pellionisz, 10th of April, 2007]

Is Biology Reducible to the Laws of Physics? [Philosophy of PostGenetics is to come]

John Dupré

Darwinian Reductionism: Or, How to Stop Worrying and Love Molecular Biology. Alex Rosenberg. x + 263 pp. University of Chicago Press, 2006.

Alex Rosenberg is unusual among philosophers of biology in adhering to the view that everything occurs in accordance with universal laws, and that adequate explanations must appeal to the laws that brought about the thing explained. He also believes that everything is ultimately determined by what happens at the physical level—and that this entails that the mind is "nothing but" the brain. For an adherent of this brand of physicalism, it is fairly evident that if there are laws at "higher" levels—laws of biology, psychology or social science—they are either deductive consequences of the laws of physics or they are not true. Hence Rosenberg is committed to the classical reductionism that aims to explain phenomena at all levels by appeal to the physical.

It is worth mentioning that, as Rosenberg explains, these views are generally assumed by contemporary philosophers of biology to be discredited. The reductionism that they reject, he says, holds that there is a full and complete explanation of every biological fact, state, event, process, trend, or generalization, and that this explanation will cite only the interaction of macromolecules to provide this explanation.

Such views have been in decline since the 1970s, when David Hull (The Philosophy of Biological Science [1974]) pointed out that the relationship between genetic and phenotypic facts was, at best, "many/many": Genes had effects on numerous phenotypic features, and phenotypic features were affected by many genes. A number of philosophers have elaborated on such difficulties in subsequent decades. ["Neurophilosophy" as a discipline was born in realization that the causal relationship of one neuron to another, and the next (in a "reflex arc") was obsolete, and in view of the emergence of massively parallel connectionism in the new discipline of "Neural Networks" the general philosophyical underpinning had to be re-crafted. Patricia Churchland (UCSD) accomplished this in her epoch-making book. In the presently ongoing new paradigm-shift, "The Philosophy of PostGenetics" is yet to find its author - undoubtedly to be catapulted into a similar career to those of the Churchlands - AJP]

The question then is whether Rosenberg's latest book, Darwinian Reductionism: Or, How to Stop Worrying and Love Molecular Biology, constitutes a useful attack on a dogmatic orthodoxy or merely represents a failure to understand why the views of an earlier generation of philosophers of science have been abandoned. Unfortunately I fear the latter is the case. More specifically, his portrayal of the genome as a program directing development, which is the centerpiece of his reductionist account of biology, discloses a failure to appreciate the complex two-way interactions between the genome and its molecular environment that molecular biologists have been elaborating for the past several decades.

In earlier work, Rosenberg accepted the consensus among philosophers of biology that biology couldn't be reduced to chemistry or physics. But whereas most philosophers saw this as a problem for philosophy of science, and for traditional models of reduction, Rosenberg concluded that it was a problem for biology, a problem indicating that the field's purported explanations were neither fundamental nor true.

However, in his most recent book Rosenberg is more sanguine about biology. As the title suggests, the new idea is that recognition of the pervasiveness of Darwinism in biology will enable us to assert reductionism after all. Rosenberg is an admirer of Dobzhansky's famous remark that nothing in biology makes sense except in the light of evolution:

Biology is history, but unlike human history, it is history for which the "iron laws" of historical change have been found, and codified in Darwin's theory of natural selection. . . . There are no laws in biology other than Darwin's. But owing to the literal truth of Dobzhansky's dictum, these are the only laws biology needs.

The suggestion is that something Rosenberg calls "the principle of natural selection" is actually a fundamental physical law. Natural selection, according to him, is not a statistical consequence of the operation of many other physical (or perhaps higher-level) laws, as most philosophers of biology believe. Rather, it is a new and fundamental physical law to be added to those already revealed by chemistry and physics. I won't try to recount Rosenberg's arguments for this implausible position.

The largest part of the book motivates reductionism from a quite different direction by defending the view that genes literally embody a program that produces development. Rosenberg introduces this view by recounting some work on the development of insect wings. There is a rather disturbing tendency in this exegesis to suggest an imputation of agency to the genes that are implementing this program. He says that the genes fringe and serrate "form the wing margin," for example, and "wingless builds wings." He also maintains that in Drosophila, "2500 genes . . . are under direct or indirect control of eyeless." As the last two examples illustrate and Rosenberg explains, genes are frequently identified by what doesn't happen when they are deleted. But Rosenberg seems quite untroubled by the dubious inference from what doesn't happen to the conclusion that making this happen is what the genes "do" when in place. These reifications provoke a range of worries, but at a minimum, a defense of such ways of speaking will need to address another growing philosophical consensus to which Rosenberg is an exception, that the gene is a concept that no longer has an unproblematic place in contemporary biology.

Rosenberg does attempt a defense of the gene, but his arguments are unconvincing. The biggest problem is that he never says what he means by a gene. He refers uncritically to estimates of the number of genes in the human genome; although he does outline some of the difficulties with these estimates, he does not seem to appreciate their force. As a positive contribution, it appears that all he has to offer is the proposal that genes are "sculpted" out of the genome by natural selection to serve particular functions. The central point of critics of the gene concept is that functional decomposition identifies multiple overlapping and crosscutting parts of genomes. The "open reading frames" to which biologists refer when they count the genes in the human genome not only can overlap but are sometimes read in both directions. Subsequent to transcription they are broken into different lengths, edited, recombined and so on, so that one "gene" may be the ancestor of hundreds or even thousands of final protein products. Sophisticated would-be reductionists, such as Kenneth Waters, have tried to accommodate this point. Rosenberg seems just to ignore it as happily as he ignores most of the literature that has expounded the difficulties (for example, What Genes Can't Do, by Lenny Moss [2003], and The Concept of the Gene in Development and Evolution, edited by Peter Beurton, Raphael Falk and Hans-Jörg Rheinberger [2000]).

The problem might have been ameliorated if Rosenberg had paid more attention to the increasingly diverse constituents recognized in the genome apart from the genes he needs to run his programs. The lack of concern with the genome is highlighted, for example, when in the course of a single paragraph he says that sculpting of the genome by natural selection has resulted in "a division mainly into genes" and refers to 95 percent of the human DNA sequence appearing to be "mere junk" (another hypothesis that has been widely rejected). It is conceivable that Rosenberg means to define genome so as to exclude the junk, although I have never encountered such a usage before. What is clear, though, is that he sees the genome merely as a repository for the informationally conceived genes supposed to run the developmental program. Attention to the increasingly understood complexities of the genome as a material object would have made the misguided nature of the enterprise much clearer.

A further problem is that some of the biology in the book is dated. For example, Rosenberg says that "there are about 30,000 to 60,000 genes in our genome," but in fact there is a fairly stable consensus now that the number is about 23,000. More striking is his remark that alternative splicing is "uncommon but not unknown," whereas it is actually widely accepted that such splicing occurs in more than 70 percent of human genes. Although Rosenberg has researched some biological topics in detail, the book contains other lapses as well. He appears to be unaware, for instance, that methylation occurs in contexts other than sexual imprinting. And I was struck by his remark that the world is now mainly populated by sexual species; in fact, the overwhelming majority of organisms now, as ever, are prokaryotes and (relatively) simple asexual eukaryotes. It is admittedly difficult or impossible to stay fully au courant with the latest in molecular biology, but a careful reading of the manuscript by a practitioner would have been very helpful.

Because I have been involved for many years in criticism of the earlier orthodoxy that Rosenberg continues to defend, it is not surprising that I am unconvinced by his reactionary argument. And it is of course very often a good thing for philosophers to confront the orthodoxies of their discipline. But the standards for undermining orthodoxy are inevitably high, and Rosenberg does not come close to meeting them.

The subtitle invites us to learn to love molecular biology. Many of the philosophers whom Rosenberg's views contradict greatly admire the achievements of molecular biology. Love, however, is well known for being blind. I would encourage Rosenberg to settle for admiration.

Reviewer Information

John Dupré [a new Founder of International PostGenetics Society] is professor of philosophy of science in the Department of Sociology and director of the Economic and Social Research Council's Centre for Genomics in Society (Egenis). His most recent book is Darwin's Legacy: What Evolution Means Today (Oxford University Press, 2003).

[Every major paradigm-shift in the natural sciences has inevitable consequences on philosophy. PostGenetics ("Genomics beyond Genes") is unlikely to become an exception. This columnist is not a professional philosopher - though contributed with his own science and interviews to "Neurophilosophy". That discipline is now on the bookshelves. "Philosophy of PostGenetics" is certain to emerge in the near future - A. Pellionisz, 5nd of April, 2007]

Trillion-dollar prize turns dotcom into watt-com

The New York Times

Silicon Valley's best and brightest have identified the next big thing: alternative energy. Matt Richtel reports.

SILICON Valley's dotcom era might be giving way to the watt-com era.

Out of the ashes of the internet bust, many technology veterans have regrouped and found a new mission in alternative energy: developing wind power, solar panels, ethanol plants and hydrogen-powered cars.

It is no secret that venture capitalists have begun pouring billions into energy-related start-ups with names such as SunPower, Nanosolar and Lilliputian Systems.

But that interest is now spilling over to many others in Silicon Valley - lawyers, accountants, recruiters and publicists, all developing energy-oriented practices to cater to the cause.

The best and the brightest from leading business schools are pelting energy start-ups with résumés. And, of course, there are entrepreneurs from all backgrounds - but especially former dotcommers - who express a sense of wonder and purpose at the thought of transforming the $US1 trillion ($1.2 trillion) American energy market while saving the planet.

"It's like 1996," says Andrew Beebe, one of the remade internet entrepreneurs. In the boom, he ran Bigstep.com, which helped small businesses sell online. Today, he is president of Energy Innovations, which makes low-cost solar panels. "The valley has found a new hot spot."

Beebe says the valley's potential to generate change is vast. But he cautioned that a frenzy was mounting, the kind that could lead to over-investment and poorly thought-out plans.

"We've started to see some of the bad side of the bubble activity starting to brew," Beebe says.

The energy boomlet is part of a broader rebound that is benefiting all kinds of start-ups, including plenty that are focused on the web. But for many in Silicon Valley, high tech has given way to "clean tech", the shorthand term for innovations that are energy-efficient and environmentally friendly. Less fashionable is "green", a word that suggests a greater interest in the environment than in profit.

The similarities to past booms are obvious, but the valley has always run in cycles. It is a kind of renewable gold rush.

In this case, the energy sector is not so distant from other Silicon Valley specialities as it might appear, say those involved in the new wave of start-ups. The same silicon used to make computer chips converts sunlight into electricity on solar panels, while the bioscience used to make new drugs can be employed to develop better ethanol processing.

More broadly, the participants here say their whole approach to building new companies and industries is easily transferable to the energy world. But some wonder whether this is just an echo of the excessive optimism of the internet boom. And even those most involved in the trend say the size of the market opportunity in energy is matched by immense hurdles.

Starting a clean technology firm is "not like starting an online do-it-yourself legal company", says Dan Whaley, chief executive of Climos, a San Francisco company that is developing organic processes to remove carbon from the atmosphere. "Scientific credibility is the primary currency that drives the thing I'm working on."

Just what that thing is, he would not specify. For competitive reasons, Whaley declines to get into details about his company's technology. His advisory board includes prominent scientists, among them his mother, Margaret Leinen, the head of geosciences for the National Science Foundation. In the last Silicon Valley cycle, Whaley's help came from his father. In 1994, he did some of the early work from his father's living room on GetThere.com, a travel site. It went public in 1999 and was bought by Sabre for $US750 million in 2000.

This time around, entrepreneurs say they are not expecting such quick returns. In the internet boom, the mantra was to change the world and get rich quick. This time, given the size and scope of the energy market, the idea is to change the world and get even richer - but somewhat more slowly.

Those drawn to the alternative-energy industry say they need time to understand the energy technology, and to turn ideas into solid companies. After all, in contrast to the internet boom, this time the companies will need actual manufactured products and customers.

"There are real business models and real products to be sold in established markets and growing economics," says George Basile, who has a doctorate in biophysics from the University of California, Berkeley, and specialises in energy issues.

Basile has just stepped into the fray himself. In January, he became the executive adviser for energy issues at Bite Communications, a San Francisco public relations firm with scores of technology clients that is now working to attract energy start-ups.

The sudden interest of lawyers, accountants and other members of the wider valley ecosystem strikes some as opportunistic.

"There's a large amount of bandwagon-jumping right now," says Mark Hampton, chief executive of Blanc & Otus, a technology-oriented public relations firm whose clients have included TiVo, Sybase and Compaq. Still, he understands the interest of relative newcomers: "There's a huge opportunity."

They are all, plainly, following the money. In the first three quarters of 2006, venture capital firms put $US474 million into a broad range of valley start-ups in energy storage, generation and efficiency, according to Cleantech Venture Network, an industry trade group. Energy was by far the fastest-growing area, and the amount was on par with what was put into telecommunications and biotechnology.

Yet the amount of money involved is still relatively small compared with the boom years. Over all, venture funding last year was still less than a third of the nearly $US34 billion venture capitalists invested in the region in 2000, the peak of the bubble, according to the Centre for the Continuing Study of the California Economy, based in Palo Alto.

"This is not 2000. It doesn't feel like 2000 on the street," says Stephen Levy, the centre's director. But, he says, "there's no doubt there's a buzz".

[1996 in Silicon Valley was characterized by three subsequent steps; the decision of government releasing the "Internet" to private business, establishment of the first widely successful applications of a browser company (Netscape) and search engine (Yahoo) - to be followed a year later (2007) by the first major e-trade company (Amazon). Somewhat similarly, the PostGenetic era (whole genome - beyond genes) was opened for business by Celera (whole human genome), and by 2006 "Big Pharma" became volume buyer of "non-coding" short repetitive sequences. A "boom" develops when there is a competition for essentially the same resources. With the Internet, e-information and e-commerce competed head-to-head for developers. With the "Big Pharma sector" now not alone, but competing with "Bioenergy" sector, "regulatory DNA" (the key to understanding genome function to enable modified and synthetic genomes) is fiercely competed for by two essential, yet independent sectors. Prices will skyrocket - A. Pellionisz, 2nd of April, 2007]

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'Junk DNA' Offers Up Prostate Cancer Clues

Scientists say important new genetic findings open up fresh areas of research.

By Mary Carmichael

Newsweek

April 1, 2007 - Prostate cancer is a disease that runs in families—if your grandfather had it and your father had it, you're at a higher risk than average of getting it, too—so it's always been clear that flaws in DNA play an important role. But for over a decade scientists have struggled to find genes that contribute to the disease. Instead, they've mostly found false alarms, candidates that have been implicated in one study and just as quickly discarded in the next. "We've known there was a genetic component," says National Cancer Institute researcher Stephen Chanock, "but we've had no robust, strong finding that everyone could agree on."

According to three new studies published Sunday in Nature Genetics, though, those days are over. Three separate groups of scientists have pinpointed seven variations in DNA that definitely increase a person's risk of prostate cancer. All of the variants are found on the same chromosome. But don't call them "prostate cancer genes"—the reason scientists couldn't find those before, it seems, is that the culprits turned out not to be genes at all. Instead, they are found in so-called "junk DNA," portions of the genome that don't make proteins. "What these variants are doing inside the cell is still a big question," says Brian Henderson, dean of the school of medicine at the University of Southern California. "But whatever we've found, it's the same finding by three different groups who didn't find anything else. After 15 years of looking, that's very exciting, believe me."

One of the studies, led by Henderson, David Reich of Harvard Medical School and others, lays out where the seven genetic variations are. All appear in seemingly barren stretches of chromosome 8 with virtually no genes. The other two studies confirm the location of the prostate-cancer risk factors and show independently that they do influence a person's risk for prostate cancer. In the uncertain world of prostate cancer, that confirmation is crucial, says William Catalona, a urologist and surgeon at Northwestern University who coauthored the second paper with the Icelandic firm deCODE Genetics. "One of the problems that has plagued prostate cancer is that nobody can ever confirm anybody else's work," Catalona says. "You'll have a really good research group saying, 'We have a signal here,' and then everyone else will try to reproduce that signal and they can't. So people get skeptical and think that it's a false positive signal, and in genetics, false positive signals occur all the time."...

Increasingly, though, research has been revealing that "junk DNA" is a misnomer [International PostGenetics Society was the first organization that formally abandoned the "Junk DNA" dogma 1972-2006 - AJP]- it seems instead to play a key role in regulating the amount of proteins made by certain genes. The variants linked to prostate cancer may be involved in this type of regulation. They could influence, for instance, the activity of a gene called MYC, which controls cell division and has been linked to many different kinds of cancer. It, like the variants, is found on chromosome 8. "Everyone has a high level of suspicion about MYC. Could what we're finding be related to that gene?" wonders Henderson. "Maybe there's some long, distant effect it's having that we don't understand and don't have any prior knowledge of."

Alternately, the seven variants might be linked to an unusual property of chromosome 8, one that becomes clear only when a cell is cancerous. Tumor cells have genomes that look different from healthy cells; they develop mutations that enable them to thrive at the expense of the rest of the body. In almost all types of tumor tissue, including prostate tumors, says Chanock, "All hell breaks loose in this region where the variants are found." Healthy cells have two copies of chromosome 8; some tumor cells may have as many as 10 copies of this region. Perhaps, says Reich, "these genetic variants could be increasing the propensity of the DNA in this region to copy itself."

For scientists, then, task No. 1 is to explore the new biology they've found. "These discoveries may provide us with new markers and blood tests for prostate cancer susceptibility and aggressiveness," says Catalona, "as well as possible new targets for treatment and even prevention." However, it is far too early, adds Chanock, for clinicians to get involved. "Right now, we're a long way away from testing people for these variants and judging their risk by it. It would be challenging to determine exactly what you would say to counsel someone before and after the results of such a test," he says. But further down the road, he says, doctors will indeed be able to test men for these seven genetic variants and others, determining who's really at risk.

[Prostate cancer is just one of the exploding number of "junk DNA diseases" and the list is growing longer by the day. Looking "beyond genes" in PostGenetics is, therefore, not only a "PostModern era", but a compelling reason to re-align priorities in R&D and resource allocation. Hundreds of millions of diagnosed and yet-to-be-diagnosed people affected with such diseases is a responsibility that can not be ignored without consequences - A. Pellionisz, 5th of April, 2007]

Cancer epigenomics: DNA methylomes and histone-modification maps

Manel Esteller

An altered pattern of epigenetic modifications is central to many common human diseases, including cancer. Many studies have explored the mosaic patterns of DNA methylation and histone modification in cancer cells on a gene-by-gene basis; among their results has been the seminal finding of transcriptional silencing of tumour-suppressor genes by CpG-island-promoter hypermethylation. However, recent technological advances are now allowing cancer epigenetics to be studied genome-wide — an approach that has already begun to provide both biological insight and new avenues for translational research. It is time to 'upgrade' cancer epigenetics research and put together an ambitious plan to tackle the many unanswered questions in this field using epigenomics approaches.

The epigenetic landscape of cancer cells is profoundly distorted. Human tumours undergo a massive overall loss of DNA methylation, but also acquire specific patterns of hypermethylation at certain promoters. In addition, these DNA-methylation changes are linked with the presence of an aberrant pattern of histone modification. Small-scale studies of epigenetic marks have provided important insights into cancer biology; for example, the hypermethylation of tumour-suppressor genes, which is associated with their transcriptional silencing, is recognized as a key feature of cancer pathogenesis. However, several important unanswered questions remain. How many genes undergo epigenetic disruption in a given tumour? Do these changes differ between distinct types of cancer cell? What are the molecular and genetic mechanisms that underlie these altered epigenetic profiles? And can a more global knowledge of the epigenetic characteristics of cancer cells be used for translational purposes?

Many of these questions can be answered by applying 'omics' approaches to cancer epigenetics. Here I provide a broad picture of how our current knowledge of epigenetic defects in cancer cells is beginning to be extended following the recent advent of genome-scale technologies to map DNA methylation and histone modifications. I begin by providing a brief overview of the current understanding of how epigenetic alterations contribute to tumorigenesis, and then discuss the powerful high-resolution epigenomics approaches that are extending these findings. This is followed by an exploration of the biological insight that is emerging from epigenomic studies of DNA methylation and histone modification patterns in cancer cells, and the prognostic, diagnostic and therapeutic impact of epigenomic profiling. I conclude by discussing the future of cancer epigenomics in the light of large-scale, coordinated efforts to catalogue the human epigenome.

[The "Methylation prediction of FractoGene" provides with a systematic exploration of "Gene/PostGene relations - A. Pellionisz, 2nd of April, 2007]