The dynamic and reversible phosphorylation of tyrosine residues is a key feature of intercellular communication. Through the regulated activities of kinases and phosphatases, cells are primed to respond to changes in their environment. The receptor tyrosine phosphatases (RPTPs), which function at the cell surface, have been implicated in diverse aspects of biology from lymphocyte signalling to neurite outgrowth to vascularisation, however, their signalling principles remain to be determined. We recently identified high confidence substrates for the receptor, PTPRK, that are related to cell-cell adhesion and actin dynamics1. We showed that the PTPRK extracellular region is responsible for its subcellular localisation, that PTPRK is highly selective and that substrate recognition is mediated in part by its membrane distal pseudophosphatase domain. We are now gaining insight into how PTPRK impacts on cell behaviour and plan to expand these approaches to other receptors.
There are three LAR family receptors in Humans: PTPRD, PTPRF and PTPRS. Loss of the single fly ortholog of this family results in lethality. In mice, these receptors regulate processes such as mammary gland development and neurite outgrowth. The receptor PTPRF localises to focal adhesions in mammary epithelial cells and has been suggested to regulate their activity. We hypothesise that PTPRF localises to focal adhesions through its extracellular domain, and binds to and dephosphorylates key focal adhesion regulators, similarly to PTPRK and adherens junctions. This project will use unbiased approaches to identify substrates of PTPRF and to characterise phenotypes associated with its loss or mutation. The project will develop by using 3D cultures, for example skin equivalents or mammary spheroids, to explore its function. We are particularly interested in the impact of aging on phosphatase activity and tissue homeostasis, for example, as a result of oxidative stress.
cell biology/development; molecular biology
PhD Student Opportunities 2020
The Babraham Institute is a world-leader in fundamental biological research investigating the systems that underpin development and healthy ageing. It is a recognised postgraduate University Partner Institute of the University of Cambridge. Starting October 2020 a number of Studentships will be available leading to a University of Cambridge PhD degree. These studentships can be awarded for up to 3.5 or 4 years. In addition, studentships funded by a range of University of Cambridge funding schemes can be held at the Babraham Institute (see the student pages of our website here - https://www.babraham.ac.uk/vacancies-training/phd-programme
) and for specific funding sources for EU and overseas graduate student at Cambridge, please visit here - http://www.graduate.study.cam.ac.uk/finance/funding
Please see our website (http://www.babraham.ac.uk/
) and the BBSRC website (https://bbsrc.ukri.org/skills/
) for details of eligibility and funding. Non-EU nationals must find funding for academic fees and personal support. In cases where applicants must find their own funding, we will require evidence that the level of funding is at least equal to the standard BBSRC/MRC PhD funding package.
Students will join a thriving scientific community situated on an attractive parkland campus near Cambridge. Our 60 students are all members of Cambridge Colleges and participate fully in University social and academic life - https://www.gradschl.lifesci.cam.ac.uk/
Details of our interactive scientific programmes can be found on the Babraham Institute website - http://www.babraham.ac.uk/
As a student at the Institute, you will have access to all of our outstanding science facilities (https://www.babraham.ac.uk/science-services
), each one providing specialist equipment and expertise to support key research techniques and technologies. In addition to our animal facility, imaging, chemical synthesis and mass spectrometry we are able to offer transgenics services, flow cytometry, lipidomics, next-generation sequencing and a highly specialist team of bioinformaticians. In addition, several of our facilities operate training programmes to help you develop your own skills in these key research areas. The Institute’s research groups also incorporate a selection of other cutting-edge specialties including single-cell and multiomics approaches.
All applications for PhD Studentships at the Babraham Institute need to be made using the University of Cambridge Graduate Application Portal regardless of funding source: https://www.graduate.study.cam.ac.uk/
Please see the “Applying for a PhD” pages on our website for further details of the application process: https://www.babraham.ac.uk/vacancies-training/phd-programme/phd-applications
Short-listed applicants will be invited to attend our Institute Graduate Open Day on Wednesday 22nd January 2020 for a series of interviews. This will give applicants an opportunity to meet Group Leaders and their research groups, as well as receiving a tour of our research facilities. Reasonable travel expenses will be paid to those invited.
Students will not be able to take up an award unless they meet all University eligibility criteria and are successful in securing admission to the University. In addition, they will not be able to apply for a visa (if needed) until they hold an unconditional offer from the University.
The deadline for submission of applications via the Graduate Application Portal is 3rd December 2019. Incomplete applications will not be considered.
If you would like more information, or have any questions not answered on our website or the University of Cambridge Graduate Admission site, please contact us:
Graduate Studies Assistant, Babraham Institute, Babraham Research Campus, CB22 3AT or email to [email protected]
An Equal opportunities employer. An Institute supported by the Biotechnology and Biological Sciences Research Council http://www.babraham.ac.uk