Genome organization and cell plasticity in development and disease

Murphy Lab

Every cell has to contend with the balancing act of having a highly heterogeneous and dynamic nuclear environment and needing robust gene expression programming. This is especially important during development where cells need to simultaneously “remember” their current state, but also rapidly “forget” this state as they  respond to different developmental cues. We ask the question of “how do cells leverage this nuclear heterogeneity as a benefit to their developmental programming?” In particular, we focus on the role of chromatin organization in governing epigenetic memory and cell-type plasticity. 

In recent years it has become clear that the traditional view of heterochromatin as an inaccessible structure in the nucleus is giving way to a more dynamic picture where epigenetic regulators (like Polycomb and HP1) can tune their chromatin organization in a way that promotes memory and maintenance of repression rather than structural repression. We endeavor to understand this feedback between epigenetic regulators and chromatin organization at a molecular and biophysical level. Our favorite suite of tools are home-built microscopy systems that enable multiplexed sampling of both the transcriptional state and chromatin folding at single-cell spatial resolution. We leverage stem cell culture, organoid models of gastrulation, and mouse embryos to build quantitative models of gene regulation specifically focusing on the biophysical properties of chromatin.  

As a group, we are committed to: 

1. Engaging in rigorous, reproducible, and thoughtful science .
2. Creating an inclusive environment that supports individuals, regardless of background, to their next career steps.
3. Fostering a collegial and professional lab environment where everyone is able to work to their full potential.