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Dynamics of DNA base-pair breathing, telomere loss and telomere clustering

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SDBW04 - Spatially distributed stochastic dynamical systems in biology

We start by analysing a model of base-pair breathing in DNA using a system of stochastic ordinary differential equations to describe the distances between bases in a sequence of bases that contains a defect.  We describe how the parameters in the SODE model are obtained from  all-atom MD simulations (AMBER) using a maximum likelihood algorithm.  The result is a model which explains how base-pair breathing depends on the twist of the double helix.  This work is in collaboration with Cipri Duduiala, Ian Dryden and Charlie Laughton (Phys Rev E, 80, 061906, 2009 and Physica D 240, 1254-1261, 2011). 

Telomeres are sequences of bases at the ends of chromosomes.  During replication, they are shortened due to imperfect replication of the DNA .  We present a variety of models of telomere loss, using an evolving distribution of telomere lengths, and analyse this mechanism of aging in cell populations using a combination of theoretical and analytical techniques. This work formed part of the PhD thesis of Qi Qi, cosupervised by Helen Byrne ( and Bull Math Biol 76, 1241, 2014).

Finally, we  outline ongoing work modelling (in collaboration with David Holcman) on the formation of protein-telomere clusters in yeast cells, using coagulation-fragmentation equations to describe the cluster size and composition. 

This talk is part of the Isaac Newton Institute Seminar Series series.

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