Identifying and characterizing transcriptional silencers

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.