"Knowing the parts of isolated entities is not enough. A musical metaphor expresses it best: molecular biology could read notes in the score, but it couldn’t hear the music." - Carl Woese, A New Biology for a New Century (2004)

"Chance events—injuries, infections, infatuations; the haunting trill of that particular nocturne—impinge on one twin and not on the other. Genes are turned on and off in response to these events, as epigenetic marks are gradually layered above genes, etching the genome with its own scars, calluses, and freckles." - Siddhartha Mukherjee, The Gene: An Intimate History (2015)

Nothing about development in multicellular organisms makes sense except in the light of epigenetics. It captures the remarkable capacity for cells with identical genomes, such as the billion or so cells in our bodies, to differentially regulate their genes and retain these patterns of expression throughout the life of the organism. This process of establishing epigenetic gene expression states is intricately tied to how the genome is organized and packaged by proteins called histones. Molecular labels in the form of histone modifications constitute a major pathway that bookmarks gene expression states in eukaryotic cells without alterations to the underlying DNA sequence. Using yeast as a model system, my laboratory takes a highly interdisciplinary perspective that synthesizes genetics, biochemistry and biophysical approaches to define how cells encode and transmit heritable patterns of gene expression.    

PROJECT 1:

ENCODING STABLE EPIGENETIC STATES

Metabolic processes within the nucleus such as DNA replication and mRNA transcription are accompanied by histone turnover and the continuous reorganization of chromatin structure. In the face of an epigenetic landscape that is dynamic and in constant flux, how do cells ensure the reliable transmission of epigenetic information across multiple generations? We are interested in two aspects of this question: 1) What are the rules that underlie the inehritance of silent and active epigenetic gene expression states? 2) What is the network of protein-protein interactions that enforces these rules? We will use a combination of genetic and biochemical approaches to address these questions.

PROJECT 2:

CAPTURING THE DYNAMIC EPIGENOME

Post translational modifications of histones act as a signaling platform to recruit evolutionarily conserved proteins that can read, write, and erase specific histone modifications. Although interactions between chromatin associated proteins and modified chromatin domains occur on timescales ranging from milliseconds to seconds, their concerted action results in the establishment of gene expression states that can last from hours to days. How do cells integrate such high frequency inputs to establish stable gene expression states? We are interested in capturing the transient and dynamic interactions that continuously reorganize the position, structure and composition of nucleosomes using single molecule and single cell approaches.