Biophysics of genome structure and function

This 4-year PhD studentship is offered in Dr Frank Uhlmann’s Group based at the Francis Crick Institute (the Crick) & Dr Maxim Molodtsov’s Group based at University College London position

Gene expression, chromosome segregation and DNA repair all depend on a chromosomal multiprotein complex, called Cohesin. In dividing cells, Cohesin keeps the sister chromatids together until anaphase, ensuring high fidelity of cell division. In interphase cells, Cohesin physically organizes DNA by generating chromatin loops and topologically associated domains. These functions are thought to rely on the ability of Cohesin to encircle DNA topologically and move along DNA. However, how Cohesin mechanistically interacts with DNA at the molecular level and how it generates forces necessary to keep together and rearrange DNA is poorly understood.

This project will be a collaboration between Frank Uhlmann’s and Maxim Molodtsov’s laboratories. The student will take advantage of the biochemical expertise in the Uhlmann lab to generate and characterize recombinant Cohesin as well as Cohesin regulatory proteins. These will then be used for real-time single-molecule fluorescence and force spectroscopy to study the dynamics and mechanics of cohesin molecules on DNA at single molecule level using the expertise provided by the Molodtsov lab.
The student will analyse single molecule data and interpret the results. Quantitative mathematical and biophysical input will contribute to develop a molecular model of cohesin function. The results of these approaches will provide fundamental mechanistic insights into how an essential chromosomal protein complex controls the spatial organization of genomes with implications for a wide range of chromosomal functions.

Talented and motivated students passionate about doing research are invited to apply for this PhD position. The successful applicant will join the Crick PhD Programme in September 2019 and will register for their PhD at UCL.

Applicants should hold or expect to gain a first/upper second-class honours degree or equivalent in a relevant subject and have appropriate research experience as part of, or outside of, a university degree course and/or a Masters degree in a relevant subject.

APPLICATIONS MUST BE MADE ONLINE VIA OUR WEBSITE (ACCESSIBLE VIA THE ‘APPLY NOW’ LINK ABOVE) BY 12:00 (NOON) NOVEMBER 13 2018. APPLICATIONS WILL NOT BE ACCEPTED IN ANY OTHER FORMAT.