Functional consequences of disrupting RNA-binding protein function for oogenesis and oocyte-to- embryo transition.
Primary supervisors: Chih-Jen (Lance) Lin and Nicola Gray
Day to day supervisor: Richard Smith
Tight control of gene expression is critical to life and is achieved by a combination of transcriptional and post-transcriptional regulatory mechanisms. However during certain stages of gametogenesis and post-fertilisation development, transcription is essentially inactive meaning that gene expression is controlled exclusively by post-transcriptional mechanisms. This involves the activation, repression or destruction of pre-existing mRNAs in the cytoplasm by RNA-binding proteins. Recent studies have revealed that mammals encode over 1000 functional RNA-binding proteins but despite critical links between this large class of proteins and a wide range of diseases including reproductive, metabolic, neurological and oncogenic disorders, information on their functions is only available for a handful of RNA-binding protein families. These include the DAZ family of which DAZL is the best studied and is required for male and female gametogenesis in a variety of model organisms (reviewed in PMID: 19225045) and also has an additional role in the oocyte to embryo transition in mammals (PMID: 21460039).
Here we aim to explore the functional consequences of DAZL mutations identified in human patients with reduced fertility (ovarian insufficiency, defective spermatogenesis) on the regulation of mRNAs required for meiosis and the transition to mitosis. Our preliminary data leads us to believe that these mutations may be causative and the first aim of this project is to extend these data into mouse oocytes and embryos to determine whether they are sufficient to disrupt oogenesis and oocyte-to-embryo transition. The second aim is to understand how different mutations in DAZL disrupt its different functions in regulating mRNAs (PMID: 16278232, 16001084, 17526644, unpublished) focusing on its interactions with other key RNA-binding protein families. This project will involve a wide variety of molecular biology techniques and advanced Assisted Reproductive Technologies (e.g. isolation, in vitro maturation and in vitro fertilisation of mouse oocytes, and micromanipulation etc.).
The Little France Campus
The MRC Centre for Reproductive Health (CRH) is located on the ground floor of the Queen’s Medical Research Institute on the University of Edinburgh’s Medical Campus at Little France. The MRC CRH enjoys close collaborative links with the other Centres on the Little France Campus including the MRC Centre for Inflammation Research (MRC-CIR); the British Heart Foundation Centre of Excellence in Cardiovascular Science (BHF-CVS), the Clinical Research Imaging Centre (CRIC) and the MRC Centre for Regenerative Medicine (CRM). The campus has a thriving postgraduate community.
Applicants are expected to have a good honours degree in the sciences (biological, chemical or physical), at least UK level of 2.1 or the equivalent from non-UK universities. A Master’s degree in a relevant subject would be an advantage.
How to apply?
Please submit a CV through the Admissions Enquiries form below.
A ‘statement of purpose’/personal statement and details of 3 academic referees will also be requested.
Application deadline 15 February 2016.
Interviews are expected to take place during early March 2016, the successful applicant beginning studies in September/October 2016, providing funding has been secured.
The 3 year MRC funded studentships are open to outstanding UK science graduates wishing to pursue a career in Reproductive Health. The studentship will cover fees at the UK/EU rate and a minimum stipend as directed by the MRC.
This research project will be in direct competition with 7 other projects currently on offer at the MRC-CRH. Usually the project with the best applicant/s will be awarded the funding. The funding is available to UK graduates who can demonstrate ordinary residence in the UK as defined at through the link below.
How good is research at University of Edinburgh in Clinical Medicine?
FTE Category A staff submitted: 206.93
Research output data provided by the Research Excellence Framework (REF)
Click here to see the results for all UK universities