Structure/function studies of the novel oocyte-secreted factor cumulin.

Project Description
We are looking to recruit a PhD student with the relevant biochemical, cell biology, biomedical science background to work on a project focussed on characterizing novel biologic agents in the area of reproductive biology.
The project continues on from our labs landmark paper on the production and initial characterization of the novel growth factor protein Cumulin (Mottershead et al., 2015, J. Biol. Chem. 290:24007). This protein is made up of a heterodimer of the two related proteins BMP15 and GDF9, two members of the TGFbeta family of proteins. These are oocyte-secreted proteins which are essential for fertility in mammals, and which act directly on the cells surrounding the oocyte, the granulosa cells. The action of these proteins is essential for the production of a healthy developmentally competent oocyte. We showed in our Cumulin paper that human GDF9 does not act on its own, but only as a heterodimer with BMP15. As this was only an initial characterization of the this protein there is still a great deal to be done in this area.
A focus of this project will initially be on the purification of the Cumulin heterodimer away from any free homodimeric BMP15, as the current procedure results in a mixture of these two proteins. This will be facilitated by the recent acquisition of an Akta chromatography system by our laboratory, opening up various column chromatography approaches to be used. The purified Cumulin protein will then be characterized both physically (e.g. via mass spec analysis) or biologically (for effects on granulosa cells). There will be possibilities to investigate the signalling pathways utilized by Cumulin as well as the granulosa cell responses in terms of proteins produced. This project gives scope for collaborative interactions with other investigators within the UK as well as abroad, especially to investigate the reproductive biology applications of the proteins produced.
Please quote ISTM2018-CUMO_01 on your application
Funding Notes
Self-funding students only