PI Profile

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Personal Statement

The Mirny Lab integrates quantitative, physics-based computational and theoretical methodologies with the analysis of genomic data to tackle fundamental biological questions with wide implications for health and disease. Our research objectives are twofold: (1) To elucidate the physical and molecular mechanisms of the 3D chromosome organization, and their reorganization throughout the cell cycle, during development, aging, and disease. (2) To uncover the role of this organization in cellular physiology, specifically how the 3D folding of the genome facilitates the storage, retrieval, and modification of genetic and epigenetic information. More specifically, we aim to unravel mechanisms that allow the “regulatory genome” to control the “protein-coding genome.” In recent years, we have identified two major mechanisms underlying genome organization — loop extrusion and compartmentalization — although their functional roles remain largely unexplored. We hypothesize that it is not merely the 3D organization itself but the operation of these mechanisms that is crucial for various cellular functions. For instance, loop extrusion likely plays a role in facilitating and targeting long-range genomic interactions, while compartmental phase separation might serve to store epigenetic information. Over the next five years, our goal is to deepen our understanding of these folding mechanisms in living cells and uncover their functional roles. Key to this endeavor are collaborations with leading experimental groups and the exploration of diverse biological systems. We suspect that these folding mechanisms may allow cells to perform complex information processing and learning of cellular environments and experiences.

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