Animal genomes contain thousands of genes, each of which contains the instructions for
some of the basic building blocks of cells. These building blocks termed proteins can
perform highly diverse functions and confer unique properties to the cells that activate the
respective gene, i.e. express the protein. Gene activation has been intensely studied over
the past decades, while the reverse scenario - gene repression or silencing - remains much
less well studied and thus mysterious. While the genomes activating elements, the so-called
enhancers, have been widely studied and characterized, their gene-silencing counterparts
have not been equally well explored. Only a few such silencer elements are known, and
their mechanisms of function are unknown.
This research project sets out to identify and study silencers, using the fruit fly, Drosophila
melanogaster, as a model. Using a combination of techniques spanning genomics, molecular
biology, and biochemistry, together with rigorous computational analyses, the project
intends to identify silencers and determine their chromatin and sequence characteristics and
their mechanisms, including the specific proteins that mediate their silencing functions.
Furthermore, the project will explore the specific roles of these silencers in model cell lines
and during fly development. This will involve analyzing the impact of silencer deletions in
Drosophila embryos and adult flies with regards to any potential (developmental)
phenotype.
Overall, this project will reveal novel types of elements and mechanism central to gene
regulation and animal development. Shedding more light on the repressive counterparts of
the widely studied enhancers will advance our understanding of gene regulatory
mechanisms and how they are employed in animals and humans.