Characterising genomic regulation in human pancreatic development.

Lead supervisor: Prof Jon Mill, College of Medicine and Health, University of Exeter
Additional supervisors:
Prof Noel Morgan, College of Medicine and Health, University of Exeter
Prof Andrew Hattersley College of Medicine and Health, University of Exeter

Due to a major recent award, applications are invited from students wishing to further their scientific careers by undertaking a PhD in a diabetes related area of research. Up to six studentships will be fully funded from autumn 2019 with enhanced stipends funded from a new £6million award. This award reflects Exeter as a world renowned centre of excellence for diabetes research.

Students can select from any of the advertised 16 projects. These projects have been carefully selected to provide students with an excellent scientific training in an important area of diabetes research, the latest laboratory and computing skills, outstanding resources, and with world leading scientists as supervisors. They cover various aspects of diabetes research, including autoimmunity in the pancreas; neuro-endocrinology to understand the relationship between the brain, mental health and the endocrine system; gene regulation in the placenta and fetal development of the pancreas; rare genetic forms of diabetes; muscle physiology; and the use of electronic medical records to understand disease causes, treatments and progression. Students will learn a wide range of state-of-the-art techniques, which could include CRISPR-Cas9 gene editing, DNA methylation, DNA sequence analysis, muscle insulin sensitivity physiology, brain electrophysiology, medical statistics, R for statistics and data visualisation and programming in python, data science including machine learning, in vivo metabolic phenotype skills and cell biology including 3D stem cell culture. Students will have access to outstanding resources, including cohorts of >5000 patients with rare defects in insulin secretion, a world leading collection of samples for study of pancreas pathology, resources of electronic medical records and biobanks from millions of people and unique resources for studying human development of the pancreas and brain.

Project description:
This studentship will investigate gene regulation during development of the human pancreas. The student will measure gene expression and epigenetic marks in human fetal pancreas samples and use this information to interpret genetic findings in studies of diabetes.

Despite advances in elucidating the genetic basis of diabetes there remains uncertainty about the specific causal genes involved in pathogenesis and how their function is developmentally regulated. Development of the pancreas involves spatially- and temporally-coordinated changes in gene expression, although the precise molecular mechanisms underlying this process have not been fully described. Many variants associated with diabetes are hypothesized to influence gene regulation rather than directly affecting protein structure; because regulatory genomic signatures are cell- and developmental-stage-specific, it is critical these relationships are explored in relevant tissue-/cell-types and the correct point in development.

In this project the student will undertake a systematic analysis of genomic regulation across pancreatic development, employing cutting-edge genomics technologies and systems biology approaches to profile human fetal pancreatic samples. Building on previous work from our group describing gene regulation and molecular quantitative trait loci in the fetal brain, the student will also characterize genetic effects on gene regulation during pancreatic development, facilitating the interpretation of genetic findings for diabetes and other related disorders.

The student should be interested in genomics and gene regulation, and comfortable with data and statistics. She or he will undertake both laboratory work and data analysis and learn a wide range of experimental and bioinformatic skills. The student will join a vibrant, diverse and interdisciplinary research team studying aspects of gene regulation in disease (see www.epigenomicslab.com).