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EMBL, Exiqon, Cenix, CellCentric, Duke University, Harvard University

EMBL, Exiqon Sponsor miRNA Profiling Course
The European Molecular Biology Laboratory, in collaboration with Exiqon, has scheduled a course on conducting high-throughput microRNA profiling experiments for late summer.
According to EMBL, the course will include tutorials on setting up microarray/miRNA profiling experiments, analyzing data using different algorithms and normalization approaches, and troubleshooting in all steps of such experiments.
Additionally, lectures will be offered covering different approaches to miRNA profiling, sample preparation, quality control for total RNA, and miRNA target prediction.
The event will be held Aug. 31 through September 5. Registration closes on Aug. 15. Additional information on the event can be found here.

Cenix Expands Drug Candidate Validation Collaboration with CellCentric
RNAi services firm Cenix BioScience said this week that it has extended an existing collaboration with CellCentric to validate epigenetic oncology drug candidates.
The new project follows a pilot study that the companies began in March under which Cenix used its RNAi-based phenotypic characterization platform to study several of CellCentric’s drug target candidates in a diverse panel of human cell lines (see RNAi News, 3/20/2008).  
Under the expanded agreement, Cenix said it will use the same RNAi platform, along with proprietary high-content assays and Definiens’ Cellenger image analysis software, to analyze loss-of-function phenotypes for “several more” oncology target candidates across a new collection of human cell lines.
Additional terms of the collaboration were not disclosed.

MicroRNAs Key to Cold Sore Virus Latency, Research Shows
New research is revealing the strategy that cold sore viruses use to remain dormant in the bodies of their hosts — and providing clues about how to drive the virus out of this dormancy and into a treatable state.
Researchers from Duke and Harvard Universities used pyrosequencing to identify a handful of microRNAs that are produced when cold sore viruses are in a latent stage of infection. They also discovered a transcription factor and a transcription activator that are silenced by two of the miRNAs. The work, published online this week in Nature, is expected to facilitate the development of better cold sore treatments and, perhaps, provide insights into treating other viruses as well.
Cold sores are caused by a virus called the herpes simplex virus 1. Bouts of cold sores occur intermittently in those who carry the virus, always in the same place. Between these outbreaks, HSV-1 can remain dormant for years, lingering in the trigeminal nerve, which innervates the face. Although active HSV1 virus can be destroyed using antiviral drugs such as acyclovir, dormant viruses evade this treatment.
“Inactive virus is completely untouchable by any treatment we have,” senior author Bryan Cullen, director of Duke University’s Center for Virology, said in a statement. “Unless you activate the virus, you can’t kill it.”
To activate the virus, though, scientists need to understand what keeps it dormant — and that has remained tricky. Scientists knew that HSV-1 produces a non-coding RNA called LAT RNA during dormancy, but weren’t sure what that RNA did.
“It was very mysterious because it was a non-coding RNA and also an unstable RNA,” Cullen told GenomeWeb Daily News, an RNAi News sister publication, this week.
Although others have predicted that herpes viruses used miRNAs to achieve and maintain latency, many questions remained about the players in this potential regulation.
In an effort to understand LAT’s function, Cullen and his co-workers expressed the RNA in human 293T cells, isolated it, and sequenced complementary DNA using 454 sequencing. They discovered that LAT RNA is actually a miRNA precursor that gets processed into four different miRNAs. One of these, miR-H2-3p, appears to silence a transcriptional activator called ICP0.
They then looked at whether that was true in vivo by isolating small miRNAs from the trigeminal nerve of HSV-1 infected mice and doing deep sequencing on cDNAs.
Again, they detected the miRNAs produced from LAT RNA. But they also found another miRNA called miR-H6 that’s believed to bind and silence a transcription factor called ICP4. ICP4, in turn, seems to control the expression of most HSV-1 genes during the virus’ active state, and turns on most HSV-1 genes.
“That was a big surprise,” Cullen said, because it means there has to be at least one miRNA precursor other than LAT that is expressed during latency. Based on these findings, the researchers concluded that, during dormancy, HSV-1 uses at least two miRNA precursors to generate miRNAs that establish and maintain viral latency.
“Obviously when you have more mRNA than miRNAs that’s not going to work,” he said. When the virus becomes active, it seems to ramp up the expression of ICP0 and ICP4 until they titrate out the available miRNA, Cullen explained, and the other viral genes are expressed.
Next, Cullen and his colleagues plan to characterize the new miRNAs to get an even better handle on what they are doing during latency. Eventually, the team hopes to exploit these findings to develop drugs that drive HSV-1 into an active — and treatable — state. For instance, it may be possible to block miRNA function using antisense reagents, which should theoretically push all of a host’s viruses into an active state that is sensitive to antivirals.
Cullen said he and co-author Donald Coen, a molecular pharmacologist at Harvard Medical School, are currently conducting mouse experiments aimed at doing just that. Although he noted that finding an appropriate drug delivery system is the most difficult aspect of using antisense reagents, Cullen expressed enthusiasm about the promise of such an approach.
“I think we’ll see more and more of this kind of thing coming down the pike,” he said.
And, Cullen added, if it works for HSV-1 the miRNA-blocking approach may also provide insights into treating other latent viruses, such as the virus that causes chicken pox in children and shingles in older adults and the herpes simplex 2 virus, which causes genital herpes.

The Scan

Study Finds Sorghum Genetic Loci Influencing Composition, Function of Human Gut Microbes

Focusing on microbes found in the human gut microbiome, researchers in Nature Communications identified 10 sorghum loci that appear to influence the microbial taxa or microbial metabolite features.

Treatment Costs May Not Coincide With R&D Investment, Study Suggests

Researchers in JAMA Network Open did not find an association between ultimate treatment costs and investments in a drug when they analyzed available data on 60 approved drugs.

Sleep-Related Variants Show Low Penetrance in Large Population Analysis

A limited number of variants had documented sleep effects in an investigation in PLOS Genetics of 10 genes with reported sleep ties in nearly 192,000 participants in four population studies.

Researchers Develop Polygenic Risk Scores for Dozens of Disease-Related Exposures

With genetic data from two large population cohorts and summary statistics from prior genome-wide association studies, researchers came up with 27 exposure polygenic risk scores in the American Journal of Human Genetics.