Discovering novel genetic causes of disorders of insulin secretion - PhD in Medical Studies (Research England DTP)

Background:
Patients with congenital hyperinsulinism and monogenic diabetes represent extreme ends of the spectrum in terms of insulin secretion. Studying the underlying genetic causes of disease in these individuals provides a unique opportunity to reveal the genetic mechanisms controlling beta-cell development and insulin secretion. Screening of the known genes does not identify a mutation in the majority of patients with these disorders; novel aetiologies remain to be discovered.

Aim:
Identify new genes and genetic mechanisms causing monogenic disorders of insulin secretion

Methods:
The student will have access to a unique cohort of >20,000 patients to identify novel genetic aetiologies. The student will utilise innovative bioinformatics methods to explore our large DNA sequencing datasets (>5,000 patients with targeted next-generation sequencing and >450 genome sequences) to search for shared genetic variation in patients with the same phenotype. The student will use cutting-edge molecular biology laboratory techniques to uncover genetic variants not detected by standard methods. These variants will be in interpreted in combination with clinical phenotyping to decide if they cause the disease.

Resources:
As well as working with the world’s largest collection of patients with these disorders the student will also have access to state-of-the-art molecular genetic laboratory facilities including Illumina, PacBio and Nanopore sequencing platforms and droplet digital PCR, and a £4 million high-performance computing facility for DNA sequencing analysis.

Skills development:
The multi-disciplinary supervisory team will help you develop bioinformatics skills for DNA sequencing analysis (Dr Laver), genetic variant interpretation (Dr Flanagan) and molecular laboratory techniques (Dr Johnson).

Who we are looking for:
We aim to recruit a highly motivated individual who is interested in understanding genetics and the causes of human disease. Having laboratory and computational skills would be advantageous but is not a necessity as they will be gained as part of the PhD.