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NWO ECHO grant for research on fickle RNA production (Leiden University/LION)

[02-02-2018]

(By: Leiden University/LION) Genes are active sometimes, and other times they remain dormant for a while. Leiden physicist John van Noort receives an NWO ECHO grant to find out how this happens.

DNA contains the blueprint for all proteins that regulate our body processes. The protein production starts with a copy of DNA in the form of RNA molecules. Based on the code in this RNA, our body produces proteins which control almost all processes within a cell, like processing nutrients and warding off pathogens. This sounds like a mechanism that is continuously at work. Yet RNA production is really a stop and start affair. Sometimes a gene is very active, and other times it will stop creating RNA for tens of seconds. How does this happen? Physicist John van Noort receives an NWO ECHO grant of around a quarter million euros to research this.

Unique combination

‘Our hypothesis is that the extent to which a gene’s DNA is folded varies, which would be why sometimes RNA is produced, and other times not,’ says Van Noort. ‘That seems straightforward, but it is an enormous challenge to actually prove this. Together with Tineke Lenstra from the Dutch Cancer Institute we have a unique combination of techniques to do this.’ Lenstra is able to image the production of each RNA molecule for a selected gene, while Van Noort masters the technique to dissect the structure of chromatin, molecule by molecule. Chromatin consists of a gene and the surrounding proteins which are responsible for folding. Together the researchers will study the chromatin structure in detail during a gene’s active and inactive periods.

Gene regulation

In the end, Van Noort wants to understand the mechanism behind gene regulation. ‘Later on that might translate into more understanding about cancer. But we’re not there yet. For that you need to look into the folding of each gene separately, because each gene probably has a unique chromatin structure. Now we first go to work to gain insight into the dynamics of a single gene. Perhaps those insights are applicable on a broader scale.’

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