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Horizon Discovery, Agios Pharmaceuticals, US National Institutes of Health, Whitehead Institute for Biomedical Research, Howard Hughes Medical Institute

Horizon Discovery Inks Alliance with Agios Pharmaceuticals
Horizon Discovery said this week that it has signed two agreements with cancer startup Agios Pharmaceuticals related to its X-Man cell-line technology.
The Cambridge, UK-based firm said that it has licensed certain X-Man cell lines, including major cancer-causing genes and their matched normal genetic backgrounds. In addition, it said that it would screen a number of Agios lead compounds on a wide panel of genotypes.
Horizon said that its technology should enable Agios to understand how key oncogenic pathways of cancer cells survive in tumors and to predict the genomic makeup of tumors in the responsive patient types.
Cambridge, Mass.-based Agios will pay Horizon undisclosed up-front and renewal fees during the term of the agreements. They expect to begin the collaboration this month.

NIH Sees Trimmed Non-competing Grants Until '09 Budget Arrives
The National Institutes of Health will begin funding non-competing grant awards at lower levels than listed on award notices until a permanent budget for Fiscal Year 2009 is passed, NIH said this week.
When President George W. Bush this week signed a continuing resolution to fund most of the federal government, including the Department of Health and Human Services, NIH reverted to a policy it held in 2006 and through 2008 when it was funded under continuing resolutions. This resolution provides funding for NIH under the terms of the 2008 appropriation.
NIH expects it will issue non-competing grant awards, “generally up to 90 percent of the previously committed level.”
NIH said that it will consider raising these levels after the final appropriation for fiscal 2009 is passed. Until then, it “expects institutions to monitor their expenditures carefully during this period.”

NIH to Continue at 2008 Funding Levels through March
President George W. Bush this week began Fiscal Year 2009 by signing a resolution to fund the federal government for five more months at 2008 levels.
Under the continuing resolution, most of the federal government, including the Department of Health and Human Services, which funds the National Institutes of Health and the Centers for Disease Control and Prevention, the Department of Agriculture, the National Science Foundation and others, will continue at 2008 funding levels without adjustment for inflation to cover research costs. HHS as a whole will receive an extra $150 million, which will cover salaries and expenses.
The resolution did provide appropriations for the full year of 2009 for the Department of Defense, the Department of Homeland Security, and Veterans affairs, all of which saw increases in funding that would offset or beat inflation.
“Unless the incoming 111th Congress eventually provides FY 2009 increases for NIH, NSF, and other science agencies,” according to an analyses by the American Association for the Advancement of Science, “the federal research investment in 2009 could decline for the fifth year in a row in real (inflation-adjusted) terms.”
“I am disappointed that the Congress passed a long-term continuing resolution,” Bush said in a White House statement yesterday when he signed the interim budget. “There is much work to be done, and the Congress should not adjourn for the year without finishing important business on spending, taxes, and free trade agreements.”
The resolution, which passed both the Senate and the House last week, will maintain funding through March 9, 2009.
AAAS pointed out today that Congress also did not extend the Research and Experimentation Tax Credit, which expired in December of 2008.
The White House’s budget for 2009, which the president proposed in February, called for $29.5 billion for NIH, the same amount that was budgeted for FY 2008.
The Senate has sought to add $2.1 billion to the NIH’s budget request for 2009, and passed a resolution to do so in March. Because the fiscal year has ended and in a month Americans will elect a new president, Congress is unlikely to take up the funding issue again until a new administration is in place.

Researchers Trace Small RNAs Back to Early Animal Evolution
MicroRNAs and Piwi-interacting RNAs were present in the earliest animal lineages, new research suggests.
In a paper appearing in the advanced online publication of Nature this week, an international team of researchers looked for miRNAs and piRNAs in three groups of animals that diverged from the animal family tree before the development of bilateral symmetry. They detected both types of small RNAs in a sponge — which belongs to the earliest diverging group of animals — and in a starlet sea anemone — which belongs to a group diverging slightly later. Together, the results suggest that small RNAs were around early in animal evolution.
“It appears that both microRNAs and piRNAs have been available to shape gene expression throughout the evolution of animals and perhaps even helped to usher in the era of multicellular life,” senior author David Bartel, a biologist at the Whitehead Institute for Biomedical Research and Howard Hughes Medical Institute investigator, said in a statement.
While a lot is known about the presence or absence of miRNAs and piRNAs in animals with bilateral symmetry, it was unclear whether these small RNAs are found in more basal animal lineages, lead author and Bartel lab post-doc Andrew Grimson told Cell-Based Assay News sister publication GenomeWeb Daily News.
In an effort to explore this, the researchers isolated 18- to 30-nucleotide RNAs from the starlet sea anemone Nematostella vectensis, a cnidarian, and sequenced complementary DNA libraries using high-throughput sequencing. They then flushed out miRNAs by looking for sequences that matched predictions based on bilateral miRNA pairing characteristics. “MicroRNAs make a very characteristic pattern,” Grimson said. “They really stand out.”
The researchers found 40 loci that matched all of the criteria for miRNA detection. Consistent with the notion that these represented miRNA, 31 of the loci mapped between known protein-coding genes and eight mapped within introns.
Even so, just one miRNA — miR-100 — seemed to be homologous to a bilaterian miRNA. And that miRNA contained a sequence shift that likely targets it differently in the starlet sea anemone than in other animals.
While previous research suggested that the sea anemone genome contained at least one miRNA, it was completely unknown whether the sponge — a “very, very early diverging organism” — contained any miRNAs, Grimson said.
To look even further back in evolutionary history, the researchers used the same approach to look for small RNAs in the demosponge, Amphimedon queenslandica. The researchers found eight miRNA in A. queenslandica — six mapping between protein-coding regions and two mapping within introns.
But there were differences between the miRNAs found in Nematostella and Amphimedon. For instance, the pre-miRNA hairpins found in the sponge were larger than those found in other animals. Meanwhile, those in the sea anemone were significantly smaller than bilaterian pre-miRNAs.
“In a relatively narrow spectrum of evolution microRNAs are often conserved,” Grimson said in a statement. “But in a broader spectrum they have completely changed. This suggests that microRNA evolution is more flexible and may be evolving more rapidly than suspected.”
Both Nematostella and Amphimedon also contained two classes of piRNAs. And although the researchers didn’t directly gauge miRNA or piRNA function in these animals, Grimson said, their genomes contain hallmarks suggesting that their piRNAs do target transposons.
Even so, miRNAs and piRNAs aren’t found in all animals. The researchers failed to detect either type of small RNA in Trichoplax adhaerans, a member of the placozoan group, which diverged after sponges. They did find proteins involved in the RNAi pathway, though, suggesting that miRNA genes may have been lost from the Trichoplax genome.
Whether or not miRNA contributes to bilateral complexity is still an open question, Grimson said. But, he added, the work illustrates that miRNAs and piRNAs are not a defining feature of bilaterians. Instead, the findings suggest that these small RNAs were available much earlier in animal evolution.

By continuing to explore the function and diversity of small RNAs, researchers may eventually tease apart their role in animal life over time and across lineages. “[O]ur results indicate that miRNAs and piRNAs, as classes of small riboregulators, have been present since the dawn of animal life, and indeed might have helped to usher in the era of multicellular animal life,” the authors wrote.

The Scan

Breast Cancer Risk Related to Pathogenic BRCA1 Mutation May Be Modified by Repeats

Several variable number tandem repeats appear to impact breast cancer risk and age at diagnosis in almost 350 individuals carrying a risky Ashkenazi Jewish BRCA1 founder mutation.

Study Explores Animated Digital Message Approach to Communicate Genetic Test Results to Family Members

In the Journal of Genetic Counseling, the approach showed promise in participants presented with a hypothetical scenario related to a familial hereditary breast and ovarian cancer syndrome diagnosis.

Computational Tool Predicts Mammalian Messenger RNA Degradation Rates

A tool called Saluki, trained with mouse and human messenger RNA data, appears to improve mRNA half-life predictions by taking RNA and genetic features into account, a Genome Biology paper reports.

UK Pilot Study Suggests Digital Pathway May Expand BRCA Testing in Breast Cancer

A randomized pilot study in the Journal of Medical Genetics points to similar outcomes for breast cancer patients receiving germline BRCA testing through fully digital or partially digital testing pathways.