Department of Computer Science and Applied Mathematics at the Weizmann Institute, Rehovot, Israel
Linking Genotype to Epigenotype
We are interested in understanding how biological information is encoded in DNA sequences, and how sequence variation among individuals generates phenotypic diversity. Our main focus is on transcriptional control, chromatin structure, and RNA regulation, where we aim to develop quantitative and mechanistic models that integrate the involved components, including DNA sequence, transcription factors, nucleosomes, and binding competition and synergy. To devise and validate our models, we employ several experimental methods to measure DNA binding events and gene expression on a genome-wide scale, at high temporal resolution, across single cells and cell populations, and on both native and synthetically designed regulatory sequences. Ultimately, the ability of our models to accurately explain transcriptional behaviors from DNA sequences should allow us to predict the effect that sequence variation among individuals has on gene expression and thus on more complex phenotypes and disease.