Dr Sarah Flanagan
Sir Henry Dale Fellow
Endocrinology and Metabolism
Skills Development Fellowship Vision
My vision of a successful skills development fellow is that of a highly motivated individual with a background in one of the core quantitative disciplines or in biomedical science. The primary focus for the fellow would be to explore or develop new skills which would allow them to form a niche area of research which utilises these interdisciplinary skill sets.
Initially the fellow would be trained in methods used by the hosting research groups, for example my group could offer training in bioinformatics, molecular genetics and clinical phenotyping. Once the fellow becomes competent in these areas we would seek further development of these and other complementary skills by collaborating with world-class researchers outside of Exeter. The aim would be for the fellow to be seconded to a research group for a set period of the award so that new skills could be learnt and brought back to Exeter. This would be beneficial to both the fellow and the wider research group.
The interdisciplinary nature of the project would require the fellow to have excellent communication skills and an ability to adapt to different working environments. I envisage that the fellow would initially require close supervision and guidance but as the project progresses they would start to gain the skills required of an independent researcher and as such they will start to work with some autonomy, directing their research towards their specific interests. Publishing findings and gaining skills in tasks such as supervision and grant management would also be a major focus for development as this would strengthen the fellows Curriculum Vitae in preparation for an independent fellowship application (e.g. a Career Development Award).
- PhD: Molecular Genetics, Peninsula Medical School (2005-2007)
- BSc (hons): Cancer Biology and Immunology, University of Bristol (2000-2003)
Following the completion of my PhD in 2007 I worked as a post-doctoral research fellow at the University of Exeter investigating the genetic basis of neonatal diabetes and congenital hyperinsulinism. During this period I published >125 research papers (23 first/senior author) on these opposing disorders of insulin secretion and contributed to the discovery of 9 of the 20 known genetic causes of neonatal diabetes. I was lead author for 3 of these genes. In 2015 I was awarded the EASD-SGGD Rising Star Award for my contributions to the field of diabetes genetics.
In 2014 I received a Sir Henry Dale Fellowship to take forward my work on gene discovery in congenital hyperinsulinaemic hypoglycaemia. This work complements the neonatal diabetes research being undertaken in Exeter which shares many biological mechanisms and pathways with congenital hyperinsulinism and promises to yield important findings about mechanisms of insulin secretion.
Using a combination of genome sequencing, bioinformatics and clinical phenotyping we aim to identify disease causing variants in novel genes in individuals with monogenic autoimmunity, congenital hyperinsulinism and neonatal diabetes. I have built strong collaborations with many groups working in complementary fields such as biochemistry and systems biology and the interdisciplinary approach that my team uses for gene discovery allows us to focus our efforts on interpreting variants in genes with good biological candidacy.
Once a new gene has been discovered we collaborate with research groups from around the world who perform functional studies to assess the effect of novel mutations in vitro. We also work closely with clinicians to phenotype patients. For example we will undertake extensive biochemistry studies, diet manipulation studies, neurological assessments, imaging, response to therapy and RNA studies. We have also developed strong links with physiologists who use samples collected from our patients to perform cell based studies such as developing induced pluoripotent stem cell lines and immunophenotyping.
- Flanagan SE et al. Activating germline mutations in STAT3 cause early-onset multi-organ autoimmune disease. Nat Genet. 2014 46:812-4.
- Flanagan SE et al Analysis of Transcription Factors Key for Mouse Pancreatic Development Establishes NKX2-2 and MNX1 Mutations as Causes of Neonatal Diabetes in Man. Cell Metab. 2014 19(1):146-54.
- Lango Allen H*, Flanagan SE*. GATA6 haploinsufficiency causes pancreatic agenesis in humans. Nat Genet. 2011 11;44(1):20-2. *denotes joint first authorship
Ongoing Projects & Grants
- Using the power of genetics to identify underlying mechanism of congenital hyperinsulinism in consanguineous populations. Sir Henry Dale Fellowship Wellcome Trust/Royal Society
- Targeted next generation sequencing – development of bioinformatic analysis pipelines to identify genetic variants not called by routine analysis (e.g. low level mosaic variants, large copy number variants etc).
- Monogenic autoimmunity: gene discovery and immunophenotyping of patients with known genetic aetiologies to help understand pathways of common autoimmunity.
- Prof Khalid Hussain Sidra Medical and Research Center. Doha, Qatar
- Dr Indi Banerjee Manchester Children’s Hospital, UK
- Dr Pratik Shah Great Ormond Street Children’s Hospital, London, UK
- Prof Timothy Tree King’s College London, UK
- Prof Mark Dunne University of Manchester, UK
- Prof Dame Frances Ashcroft , University of Oxford, UK
Research Group Connections