Characterising the role of kinetochore phosphoregulation

This 4-year PhD studentship is offered in Dr Peter Thorpe’s Group based at the Francis Crick Institute (the Crick).

The segregation of duplicated chromosomes during cell division is a critical process to maintain genome integrity. Errors in chromosome segregation are a leading cause of birth defects and result in aneuploidy - an incorrect number of chromosomes - which is a hallmark of cancer cells. Therefore, our lab aims to understand how the accurate separation of chromosomes is regulated.
The kinetochore is a large protein complex that assembles on chromosomes to direct their segregation during cell division. We study the regulation of the kinetochore and have identified a number of proteins that control its structure and function, in particular we found that protein modifications play a key role1-4. Kinases and phosphatases, proteins that add or remove phosphate, are recruited to the kinetochore at specific times during the cell cycle to regulate its function. We want to ask how these proteins allow cells to correctly segregate their chromosomes during cell division. We also want to ask whether specific artificially induced protein modifications can manipulate the process of kinetochore assembly and chromosome segregation.
We use a combination of high-throughput molecular and cell biology approaches in budding yeast to determine where, when and how these proteins function. For example, we will identify the target sites of specific kinases and then manipulate these sites to block their phosphorylation and determine whether these changes affect the function of the kinetochore. To assay kinetochore function we quantify the assembly of kinetochores using advanced imaging techniques and measure how accurately cells are able to separate their chromosomes. To assess the sequence of these regulatory events, we use mutants to determine the genetic dependencies of a specific modification and live cell imaging to find at what point in the cell cycle a change occures. In summary, this project is focussed on understanding the precise role of phosphorylation in regulating the kinetochore during cell division.
There will be opportunities to explore other modes of regulation during the project, for example the role of chromatin modifications. The project involves learning a broad range of skills including genetics, fluorescence microscopy, protein analysis and computational data analysis. The applicant must show evidence of excellent laboratory-based technical experience and good communication skills.

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 2017 and will register for their PhD at one of the Crick partner universities (Imperial College London, King’s College London or 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 BY 12NOON GMT NOVEMBER 14TH 2016. APPLICATIONS WILL NOT BE ACCEPTED IN ANY OTHER FORMAT.
https://www.crick.ac.uk/about-us/jobs-and-study/phd-programme/