Physics (Internal)

Statistical Mechanics of Epigenetic Landscapes

This event is part of the Departmental Seminars.

Dissertation Committee: Pankaj Mehta, Kirill Korolev, Martin Schmaltz, Ahmed Khalil, Claudio Chamon

Abstract: A common metaphor for describing development is a rugged ‘‘epigenetic landscape’’ where cell fates are represented as attracting valleys resulting from a complex regulatory network. Here, I introduce a framework for explicitly constructing epigenetic landscapes that combines genomic data with techniques from spin-glass physics. Each cell fate is a dynamic attractor, yet cells can change fate in response to external signals. The model suggests that partially reprogrammed cells are a natural consequence of high-dimensional landscapes, and predicts that partially reprogrammed cells should be hybrids that co-express genes from multiple cell fates. I verify this prediction by reanalyzing existing datasets. The model reproduces known reprogramming protocols and identifies candidate transcription factors for reprogramming to novel cell fates, suggesting epigenetic landscapes are a powerful paradigm for understanding cellular identity.