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DPhil Student 1994-97, Postdoctoral Fellow 1997-99

FionaGribble.jpgProfessor Fiona Gribble joined Frances Ashcroft’s laboratory in 1994 on an MRC Clinical Training Fellowship. Prior to her studies at the Laboratory of Physiology, she had trained as a clinician at the John Radcliffe Hospital, and then spent a year working at the Diabetes Research Laboratories in Oxford. Her DPhil involved studying the properties of the newly-cloned KATP channel. In the first instance, her work showed that the cloned KATP channel subunits generated functional currents when expressed in Xenopus oocytes. She then set about mutating different residues to establish how this affected channel function. In particular, she helped to identify where ATP bound to the pore-forming subunit to inhibit channel activity, how the sulphonylurea receptor conferred sensitivity to nucleotide activation, and how different sulphonylureas (drugs used clinically to treat diabetes) bind to the channel and block the currents. She then received an EASD (European Association for the Study of Diabetes) Eli Lilly Research Fellowship, and later a Wellcome Advanced Fellowship, to continue her work and undertake her first postdoctoral position in the Ashcroft lab for two years.

During her second fellowship, Professor Gribble moved to the University of Cambridge to set up her own lab in 1999. She decided to return to investigating the effects of the gut hormone GLP-1 on people with type 2 diabetes, an area she’d studied prior to joining the Ashcroft group. Little was known about how GLP-1 is secreted from the gut at the time. She collaborated with her husband, Frank Reimann, to study the electrophysiology of a GLP-1 secreting cell line, the success of which enabled them to establish a new research programme investigating the function of enteroendocrine cells secreting GLP-1 and other gut hormones. According to Professor Gribble: “It was a long battle. There were many hurdles to be overcome because this was a previously unexplored field and there were no protocols for studying gut endocrine cells. We worked for years generating mouse models with fluorescently labelled gut endocrine cells, as well as protocols for keeping the cells alive in culture. The perseverance paid off, and since then we have gradually built up a picture of how mouse, and more recently human, gut endocrine cells sense what we eat.” During the course of her career, she has seen GLP-1 analogues move from an idea to a widely used therapy for type 2 diabetes and obesity. She hopes that one day it will be possible to target the gut endocrine cells themselves to treat diabetes and obesity, using the knowledge her team has generated about which receptors the cells express, and how the cells function.

She was made Professor of Endocrine Physiology at the Institute of Metabolic Science in 2012. Two decades after having received her first postdoctoral Fellowship through the EASD, in 2020 Professor Gribble was elected Vice President of the Association, and its closely-related Foundation (EASD/EFSD). The EASD is of the largest networks for diabetologists worldwide with more than 5,000 active members from over 100 countries throughout the world.

View Wellcome-MRC Institute of Metabolic Science Profile

 

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