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Colloquium – Sumitabha Brahmachari, Rice University
Physical modeling of chromosomes across species: mechanistic insights and biological consequences of emergent structural features
Chromosomes are long polymers of DNA that are folded into a tiny nucleus by a concerted activity of various proteins. Quantitative understanding of the mechanistic link between protein activity, chromosome architecture, and biological function is nascent but imperative to comprehend how the DNA code governs cellular life. Establishing these links will steer biological research and yield fruitful discoveries in the physics of active polymers. In this talk, I will focus on a physical simulation framework that incorporates genomic data and furnishes mechanistic insights into regulating chromosome structure. I will discuss how this framework has been crucial in rationalizing our observations, linking the activity of specific proteins to conserved architectural features of chromosomes across species spanning the tree of life. We find that the species-wide diversity of structures emerges from a competition between three kinds of generalized forces, where the balance between these forces depends on the relative abundance of specific proteins and is a predictor of the structure. Using this framework, we further explore the elusive link between chromosome structure and crucial biological functionality like segregation or replicated DNA. The developed framework is an essential stride towards a cohesive, physics-based understanding of the chromosome architecture and its implications for cellular life.