Computational Epigenomics

All cells in our body have the same DNA sequence; yet, we consist of hundreds of distinct cell types. It is becoming increasingly clear that the epigenome, a layer of chemical modifications to the DNA and its associated proteins, is primarily responsible for these differences as it regulates which genes are turned on or off in a cell-type specific manner. Understanding how the epigenome determines cellular identity requires genome-wide measurements of its molecular components, most notably DNA methylation and histone modifications. In the past decade, technological advances have enabled high-resolution measurements of these various epigenetic marks at the genome-wide scale, leading to the construction of so-called reference chromatin state maps (epigenomes) for different species and cell types. 

However, genetic polymorphisms and environmental exposures can lead to changes in gene expression via transient and/or stable changes in the epigenome. The biomedical, agricultural and evolutionary communities are interested in understanding how these different epigenomes emerge, how stable these epigenetic changes are, and how they lead to different phenotypes. In order to answer these questions, we develop computational methods to determine what regions in the epigenome are altered under different conditions in large numbers of individuals.

At the same time, many important questions in biology and biomedicine require measurements of small cell numbers, or even single cells. This is the case for example in studies of early embryogenesis, in the analysis of cellular heterogeneity in tumors, or in the analysis of rare cell types. In the last few years, new technologies have emerged that enable genome-wide measurements of epigenetic marks in single cells and low inputs of cells. Despite these advances, the interpretation of the data produced by these single cell and low input technologies remains challenging. In our group we work to develop new computational methods for the analysis of this data.

Our group has recently moved to the ICB, and we are looking for new PhD students and postdocs to join us.