Discovering hundreds of microRNAs
Hunting for novel microRNA genes; validation of thousands of predicted candidate regions with microarrays
Dr E. Berezikov, Hubrecht Institute, Utrecht
In 2005, Eugene Berezikov, then a postdoc at Hubrecht Institute, received a Horizon grant for breakthrough research to find novel microRNAs in mammalian cells. MicroRNAs are key regulators of gene expression in cells, and at that time only about two hundred microRNA genes were known in the human genome. Berezikov applied bioinformatics followed by experimental verification. “The verification was initially carried out with RAKE assay”, he says. “The project moved along rather well, but new sequencing technologies were even more promising.” He then applied next generation sequencing technology, in particular Roche 454 sequencing. The results were very convincing. “We discovered several hundred novel microRNAs and filed a patent”, says Berezikov. “Also, we published six articles on the findings.”
Another result of the research was the establishment of InteRNA Technologies, a company that aims to find out what functions the miRNAs have and to translate this knowledge into benefits for human health.
The Horizon grants apply to 'high risk, high gain' research. In this case, there is no doubt about the outcome: it's high gain. “We achieved a pretty good result”, Berezikov acknowledges. In 2008 he received a second Horizon grant, allowing him to explore what happens if the microRNAs are shut down in a controlled manner. “This will shed light on the actual functioning of the microRNAs”, he hopes.
Fast recognition of transcription factors
Dirf: an in vivo screen to identify proteins that bind to a genomic region of interest
Dr B. van Steensel, Netherlands Cancer Institute, Amsterdam
Every cell in our body counts some 25,000 genes, which together ensure that our body does what it must. The genes are 'switched on' by hundreds of proteins, which attach themselves to a gene for this purpose. These proteins are called transcription factors. Dr K. Bas van Steensel received a Horizon grant to find a fast manner for identifying the transcription factors that switch a specific gene on or off. “For this, we use an enzyme that places a stamp on a gene. By attaching this enzyme to the transcription factors, we should be able to see at a glance which transcription factor is active.”
While the researchers have made significant progress, the end goal has not yet been reached. “The technique proved to be more difficult than thought”, explains Van Steensel. “We have, however, found a handy way of linking the stamp enzyme to transcription factor. Also, we have adopted a different, more effective approach; instead of looking at which of the hundreds of transcription factors bind themselves to a specific gene, we have chosen a single transcription factor and are looking to see to which genes it binds itself.” He is enthusiastic about the Horizon concept: "The grant is one of the few possibilities to acquire funding for 'high risk, high gain' research. As far as I am concerned, the available amount per grant may be increased somewhat, as it is difficult to conclude a truly innovative project with a relatively small budget.”