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Gautama Menon Ashoka University/IMSc, India 04:30 pm, 18 JANUARY 2021
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Biophysics Computational Biology Infectious diseases
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Can one bring to biological modelling the rigor of models in physics?
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Can one bring to biological modelling the rigor and precision of models in physics?
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What would we call progress in the quantitative model understanding of specific systems in biology?
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All of us work with mental models
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Leave out detail, capture essential features as the ultimate goal .... but what details?
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The question I've been interested in
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Metazoans
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A single cell
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What makes a simple polymer different from DNA in the nucleus of a living cell?
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Term "chromatin" coined in 1882 by Walther Flemming to
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Talk about chromatin when we discuss the
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"During the 1970s and 1980s, most researchers seemed content with the assumption that
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What we know now
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Chromosomes are not mixed at random but are found in well-defined territories
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How do we know this? Chromosome painting
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Tightly packed DNA, gene-poor
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What makes a simple polymer different from DNA in the nucleus of a living cell?
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The biophysical context
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What does it mean to say something is not in thermal equilibrium? Currents flow through
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Drive a system out of equilibrium by adding energy on a
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ATP hydrolysis
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1. Chromosomes are territorial
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Quantifying non-random arrangements?
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Challenge Predict these
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"Stylised facts"
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SR = 4TR2 PIR
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Hypothesis
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Chromatin in living cells has many energy consuming
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More active regions: Chromatin should see larger mechanical forces
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Different gene densities in
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More active: Larger fluctuations.
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Simplest model
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Simulate individual chromosomes within a nucleus
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Gene-poor, less active chromatin heterochromatin
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Experimental data
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Theoretical Predictions
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Chromosome Territories: Rabl 1885, Boveri 1908, Stack 1977
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Simulations starting from many different initial conditions.
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Centre of Mass Distribution
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Also agree with our broad understanding from lots of different measurements, which is encouraging
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Simplest model surprisingly
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GM12878
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SOM R
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Euchromatin & Heterochromatin
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DNA density distribution: 12/20
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Configurations: Chromosomes 18 and 19 2 homologs each
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Are chromosomes distributed by their gene density or by their size?
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Chromosome size
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Chromosome gene density
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GM12878 Insitu
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GM12878 TCC
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The fractional volume occupied by each chromosome, as a function of its length
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Inactive X chromosome located more peripherally than the active X
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Xa/Xi differential localizations
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A first-principles model
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Nucleolus formation Nuclear phase separation
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Collaborators
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Thank you
Description:
Explore the intricacies of large-scale nuclear architecture in this comprehensive lecture by Gautam Menon from Ashoka University/IMSc, India. Delve into the fascinating world of biophysics, computational biology, and infectious diseases as the speaker addresses the challenge of bringing rigorous physical modeling to biological systems. Learn about the complex organization of chromosomes within the nucleus, including chromosome territories and the differences between euchromatin and heterochromatin. Discover how energy-consuming processes and mechanical forces influence chromatin behavior, and examine experimental data alongside theoretical predictions. Investigate the distribution of chromosomes based on size and gene density, and explore the concept of nuclear phase separation. Gain insights into cutting-edge research on nucleolus formation and the differential localization of active and inactive X chromosomes. This in-depth presentation offers a valuable perspective on the intersection of physics and biology in understanding nuclear architecture. Read more

Understanding Large-Scale Nuclear Architecture by Gautam Menon

International Centre for Theoretical Sciences
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Gautama Menon Ashoka University/IMSc, India 04:30 pm, 18 JANUARY 2021