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Genetic determinants of pituitary adenomas


   William Harvey Research Institute


About the Project

UK home tuition fees will be paid by the funding body, however non-UK students with the appropriate funding for additional PhD fees are also eligible to apply.

This is an exciting opportunity for a 4-year Barts Charity-funded PhD studentship within the world-renowned William Harvey Research Institute at Barts and The London School of Medical and Dentistry (SMD) at Queen Mary University of London (QMUL). Applications are invited from highly motivated graduates with a BSc (First or Upper Second) or MSc (Distinction or Merit) from biological or related sciences. Previous research experience in computational genetic analysis, molecular biology techniques and cell culture would be an advantage. Applicants should have a high level of proficiency with computer software related to genetic and laboratory research, programming languages (R, python), bioinformatics data analysis and statistical evaluation, as well as the ability to organise a varied workload and to work within a team.

Project background:

Pituitary tumours can cause severe life-long disease, especially in familial and childhood-onset cases, but the genetic background predisposing to these diseases is largely unknown.

We have a large cohort of familial and young-onset cases, as well as sporadic pituitary adenoma cases and using various genetic techniques (genome wide association, exome and whole genome sequencing, whole genome sequencing), we aim to identify genetic markers which cause the monogenic forms of the disease as well as those that contribute to polygenic disease predisposition. Furthermore, data from families, either with known mutations in the AIP or MEN1 genes, or with mutations in currently unknown genes, suggest that not all family members carrying a DNA change develop pituitary tumours, representing incomplete penetrance. We hypothesise that genetic alterations predisposing for sporadic pituitary disease play a role in patients with monogenic disease with incomplete penetrance, as seen in other conditions1. The two main questions of the project are:

1.          What are the genetic/epigenetic changes that predispose to/cause sporadic, familial or childhood-onset pituitary tumours?

2.          What genetic factors lead to tumours in some mutation carriers but not in others?

The PhD candidate will perform a wealth of bioinformatics and statistical genetic analyses and identified targets will then be tested with functional molecular biology tools. Our laboratory has expertise in both of these fields of research2,3. These studies are likely to lead to high impact publications, international conference presentations and an outstanding training in these interrelated fields.

Environment and PhD training:

QMUL has an outstanding reputation for its research including in the field of pituitary diseases and the training of PhD students. WHRI, located in the centre of London, has a strong track-record in basic, translational and clinical research with unique access to large patient cohorts and samples. The PhD student will benefit from a state-of-the-art environment regarding genetically determined diseases and work with the Centre for Translational Bioinformatics at the WHRI with another 60+ scientists and close links to Genomics England. The host laboratory has a number of clinical and postdoctoral fellows who will provide an excellent training environment for the student. As well as receiving to bioinformatics and statistical genetics training and learning key genetic analysis techniques, the student will have the opportunity to learn cell & molecular biology techniques. Students will receive support to attend international and national conferences, in the fields of endocrinology and genetics.

Funding Notes:

The 4-year PhD studentship and project consumables are funded by Barts Charity with a tax-free stipend including London weighting of £24,278 (in 2022/23). UK home tuition fees will be paid by the funding body (student with appropriate funding for additional PhD fees are also eligible to apply).

All students must meet English language entry requirements, more information can be found here:

https://www.qmul.ac.uk/international-students/englishlanguagerequirements/postgraduateresearch/

Interviews are planned in the 2nd week of September 2022. The studentship is available immediately and candidates should be available to start in October 2022 or shortly thereafter.

Your application should include a Curriculum Vitae (CV) and a one-side A4 statement of purpose, setting out your previous academic or other experience relevant to the proposed research; why you wish to undertake this research at QMUL; your previous research or professional training and what further training you think you will need to complete a PhD. In addition, two referees should be named at the end of the statement. At least one reference must be from an academic referee who is in a position to comment on the standard of your academic work and suitability for postgraduate level study. Where appropriate, a second referee can provide a comment on your professional experience.

Enquiries email name and address:

Prof Marta Korbonits ()

Address: Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine, John Vane Science Building, Charterhouse Square, London, EC1M 6BQ

Application Web Page:

Applications should be sent directly to QMUL admissions via this link (choosing the category: PhD Full-time William Harvey Research Institute (non-clinical) Semester 1 (Sept Start)):

https://www.qmul.ac.uk/postgraduate/research/subjects/medicine-william-harvey-research-institute.html


References

1 Fahed, A.C., Wang, M., Homburger, J.R., Patel, A.P., Bick, A.G., Neben, C.L., Lai, C., Brockman, D., Philippakis, A., Ellinor, P.T., Cassa, C.A., Lebo, M., Ng, K., Lander, E.S., Zhou, A.Y., Kathiresan, S. & Khera, A.V. (2020) Polygenic background modifies penetrance of monogenic variants for tier 1 genomic conditions. Nat. Commun. 11, 3635.
2 Coopmans, E.C. & Korbonits, M. (2022) Molecular genetic testing in the management of pituitary disease. Clin. Endocrinol. (Oxf.).
3 Srirangam Nadhamuni, V. & Korbonits, M. (2020) Novel Insights into Pituitary Tumorigenesis: Genetic and Epigenetic Mechanisms. Endocr. Rev. 41, 821-846.

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