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Different gene densities in
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Understanding Large-Scale Nuclear Architecture by Gautam Menon
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- 1 Gautama Menon Ashoka University/IMSc, India 04:30 pm, 18 JANUARY 2021
- 2 Biophysics Computational Biology Infectious diseases
- 3 Can one bring to biological modelling the rigor of models in physics?
- 4 Can one bring to biological modelling the rigor and precision of models in physics?
- 5 What would we call progress in the quantitative model understanding of specific systems in biology?
- 6 All of us work with mental models
- 7 Leave out detail, capture essential features as the ultimate goal .... but what details?
- 8 The question I've been interested in
- 9 Metazoans
- 10 A single cell
- 11 What makes a simple polymer different from DNA in the nucleus of a living cell?
- 12 Term "chromatin" coined in 1882 by Walther Flemming to
- 13 Talk about chromatin when we discuss the
- 14 "During the 1970s and 1980s, most researchers seemed content with the assumption that
- 15 What we know now
- 16 Chromosomes are not mixed at random but are found in well-defined territories
- 17 How do we know this? Chromosome painting
- 18 Tightly packed DNA, gene-poor
- 19 What makes a simple polymer different from DNA in the nucleus of a living cell?
- 20 The biophysical context
- 21 What does it mean to say something is not in thermal equilibrium? Currents flow through
- 22 Drive a system out of equilibrium by adding energy on a
- 23 ATP hydrolysis
- 24 1. Chromosomes are territorial
- 25 Quantifying non-random arrangements?
- 26 Challenge Predict these
- 27 "Stylised facts"
- 28 SR = 4TR2 PIR
- 29 Hypothesis
- 30 Chromatin in living cells has many energy consuming
- 31 More active regions: Chromatin should see larger mechanical forces
- 32 Different gene densities in
- 33 More active: Larger fluctuations.
- 34 Simplest model
- 35 Simulate individual chromosomes within a nucleus
- 36 Gene-poor, less active chromatin heterochromatin
- 37 Experimental data
- 38 Theoretical Predictions
- 39 Chromosome Territories: Rabl 1885, Boveri 1908, Stack 1977
- 40 Simulations starting from many different initial conditions.
- 41 Centre of Mass Distribution
- 42 Also agree with our broad understanding from lots of different measurements, which is encouraging
- 43 Simplest model surprisingly
- 44 GM12878
- 45 SOM R
- 46 Euchromatin & Heterochromatin
- 47 DNA density distribution: 12/20
- 48 Configurations: Chromosomes 18 and 19 2 homologs each
- 49 Are chromosomes distributed by their gene density or by their size?
- 50 Chromosome size
- 51 Chromosome gene density
- 52 GM12878 Insitu
- 53 GM12878 TCC
- 54 The fractional volume occupied by each chromosome, as a function of its length
- 55 Inactive X chromosome located more peripherally than the active X
- 56 Xa/Xi differential localizations
- 57 A first-principles model
- 58 Nucleolus formation Nuclear phase separation
- 59 Collaborators
- 60 Thank you
