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Biophysical models of cohesin-mediated 3D genome folding and its role in DNA-based processes


   Molecular and Cell Biology

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  Prof D Panne, Prof Peijun Zhang  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

Leicester United Kingdom Biophysics Cancer Biology Medical Physics Structural Biology

About the Project

It has been proposed that DNA folding by a process called ‘loop extrusion’ by cohesin is a central organising principle of genome conformation. The hypothesis is that loop extrusion reels in genomic DNA into loops, a process which ‘individualises’ chromatin fibres and brings distant loci into proximity. The resulting higher-order packing of chromosomal DNA is thought to have important structural and regulatory consequences for chromosome segregation and other DNA-based processes.

In this project we will address how a key control factor controls the ‘loop extrusion’ process by cohesin. You will determine the underlying molecular mechanism using structural biology (cryoEM/Xray) and biochemical methods. To visualise loop extrusion in cells we will use our established cryoFIB-SEM pipeline to image the conformation of chromosomes under native conditions and at high resolution. These methods will allow you to study the impact on large-scale chromosomal features at supra-molecular detail. The project will provide fundamental insights into the mechanisms that control chromosome structure in cells. We anticipate that our work may also provide insights into the aetiology of human disorders caused by dysregulation of cohesin including congenital diseases called ‘cohesinopathies’ and genetic disorders such as aneuploidies and spontaneous human abortions.

The MRC Advanced Interdisciplinary Models (AIM) Doctoral Training Partnership (DTP) is a multi-institutional DTP between the Universities of Birmingham, Leicester and Nottingham. You will be based at the institution of the first supervisor. More information about the DTP is here: https://more.bham.ac.uk/mrc-aim/phd-opportunities/

How to apply

Information about how to apply is provided here:

https://more.bham.ac.uk/mrc-aim/phd-opportunities/

All candidates are encouraged to contact the supervisors for an informal discussion before application.

Contact for enquiries

Dr Daniel Panne [Email Address Removed]

https://more.bham.ac.uk/mrc-aim/phd-opportunities/ 


Funding Notes

This is a fully funded MRC studentship for 4 years. The funding includes a stipend, tuition fees, research/training costs and a budget to help with the cost of purchasing a laptop.
There are only a limited of places available for international applicants due stipulations set by the funders.

References

1 Li et al. Nature, (2020). 2 Tedeschi et al. Nature 501, 564, (2013). 3 Haarhuis et al. Cell 169, 693, (2017). 4 Neguembor et al. Mol Cell 81, 3065, (2021). 5 Marsden et al. Cell 17, 849, (1979). 6 Paulson et al. Cell 12, 817, (1977). 7 Naumova et al. Science 342, 948, (2013). 8 Gibcus et al. Science 359, (2018).
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