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Competitive grant to study foundations of gene expression

17 Dec 2019

The Austrian Science Fund FWF has awarded a competitive stand-alone grant of nearly 400,000 Euro to the lab of IMP Senior Scientist Alexander Stark. The funds will be used to investigate how promoters drive diverse gene expression programs in fruit flies and humans.

Alexander Stark and his lab study transcriptional regulation. This work that will enjoy a boost in support for the next three years from the Austrian Science Fund (FWF), which announced the award a 400,000 Euro "stand-alone grant".

The regulation of gene expression is a fundamental process that is essential for development, cellular differentiation and homeostasis of all living organisms. Gene expression – more specifically transcription of a gene – starts at the gene’s promoter. Promoters are diverse in sequence and display distinct regulatory specificities, but it is unknown how their functional diversity is achieved.

The successful team behind the project proposal (left to right): Leonid Serebreni, Vanja Haberle, Alexander Stark and Filip Nemcko.

Alexander Stark thinks that different types of core promoters might recruit and depend on different sets of proteins, which mediate the promoters’ distinct properties. The main objectives of the stand-alone project are to identify proteins that are differentially bound to distinct types of promoters in the fruit fly Drosophila melanogaster and humans and to test the requirement of these factors for transcription.

“While the funding scheme is for ‘stand-alone projects’, ours is a true team effort,” says Alexander Stark, highlighting the vital roles of postdoc Vanja Haberle, and PhD students Leonid Serebreni and Filip Nemcko and the essential collaboration with the IMP/IMBA’s protein chemistry facility around Karl Mechtler. “We are all very excited to start this project, it will allow us to reach a mechanistic understanding of the intriguing functional diversity of promoters we observed back in 2015.”

The Stark Lab’s project not only has the potential to identify novel factors, it also challenges the presumed universal requirement of the canonical pre-initiation complex (PIC), especially at less-well characterised core promoter types. If successful, the project will provide the first identification of proteins bound to prominent types of fly and human core promoters and may uncover presently unknown mechanisms of transcriptional initiation and regulation – which could help further our understanding of gene expression in general.

More about the research of the Stark Lab