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Theory of Living Matter Group

 

9th General Meeting

General information

This meeting will focus on statistical methods in quantitative and computational biology. Our speakers in this meeting will be Dr Ben McArthur, from the University of Southampton, and Dr Radu Zabet from the University of Essex. Both talks will be understandable for a broad scientific audience.

After the talk there will be a drinks reception with snacks and plenty of time for informal discussions.

Registration:
No registration required.

Date:
Tuesday, 28th March 2017, 6pm

Venue:
Main lecture theatre, Sainsbury Laboratory
Bateman Street, Cambridge CB2 1NN

Directions: The Sainsbury Laboratory Cambridge University is located in Cambridge University Botanic Garden and can be accessed via Bateman Street. Note that the entrance to the Sainsbury Laboratory is rather hidden in the backyard of an arts school. There will be signs and people waiting to guide the way.

Talks

“Quantitative models for transcription factor binding to the DNA”

Radu Zabet, University of Essex

In all kingdoms of life, transcription factors (TFs) are proteins that bind to specific sites on the DNA and control the expression of their target genes. Understanding where TFs bind to genome and what controls this process is pivotal to better understanding gene regulation and, consequently, to enhance our understanding of the cellular response to developmental, physiological, environmental or disease signals. We developed a statistical thermodynamics framework to model binding profiles of TFs in eukaryotic systems. One of the main advantages of the model is that it uses mathematical approximations, which allows it to predict whole genome ChIP-seq profiles in mammals within hours. Using the actual occupancy data in form of ChIP-seq profiles, we were able to estimate the number of molecules bound to the DNA for five Drosophila melanogaster TFs (Bicoid, Caudal, Giant, Hunchback and Kruppel) during early embryonic development. Our results support a model where the majority of the molecules are diffusing and are not engaged in direct interactions with the DNA (only between 10-30% of the molecules were bound to the DNA). In addition, for Bicoid and Caudal we were able to predict their binding profiles with high accuracy. Finally, we confirm that ChIP-seq experiments produce quantitative information on the level of binding of TFs to the DNA and our model is able to capture this aspect. In particular, the height of the ChIP-seq peak contains information on the amount of TF in the nucleus.


“Statistical Models of Stem Cells”

Ben MacArthur, University of Southampton

There is a long-running debate amongst stem cell biologists over stochastic versus instructive models of stem cell dynamics. In this talk I will discuss the background to this problem and show some recent data from differentiation of pluripotent stem cells toward neural progenitors which favours the stochastic perspective. Along the way I will also discuss some of the problems associated with making measurements of stochastic systems and I will show how the act of measuring using fluorescence reporters can disturb the dynamics of the system being measured, thereby presenting a basic measurement problem in cell biology. I will summarise with some suggested areas for further work that may benefit from increased collaboration between experimentalists, physicists and mathematicians.

Sponsors

This event is organised by the Theory of Living Matter Group and supported by the Company of Biologists.