09 Oct
University of Bristol
Bristol
We are seeking a Postdoctoral Research Associate to work with Professor David Murphy (Bristol Medical School), Dr Michael Greenwood (School of Physiology, Pharmacology and Neuroscience) and Dr Danijela Tatović (North Bristol NHS Trust) on an MRC-funded project entitled: ““Dynamic integration of ingestive behaviours and homeostasis by hypothalamo-neurohypophysial system glucagon like peptide 1 receptors”.
The satiety hormone GLP-1 is made in the gut and in the nucleus tractus solitarius (NTS) of the brainstem. In the clinic, pharmacological long-acting GLP-1 receptor (GLP-1R) agonists, for example liraglutide, are proving to be effective therapies in this obesity pandemic.
The GLP-1R is highly expressed in the hypothalamo-neurohypophysial system (HNS). We hypothesise that HNS GLP-1Rs integrate signals from the brain and periphery to control hormone release during periods of feeding in male and female rats. We further hypothesise that pharmacological levels of GLP-1 inhibit HNS activity by targeting the posterior pituitary (PP) as well as receptors expressed by magnocellular neurones (MCN) located in the supraoptic nucleus (SON).
In this project we will establish the long-term effects of liraglutide on the HNS proteome and phosphoproteome and ultimately identify protein changes that facilitate changes to hormone release.
For background information see:
Greenwood M, Gillard BT, Farrukh R, Paterson A, Althammer F, Grinevich V, Murphy D, Greenwood MP (2022) Transcription factor Creb3l1 maintains proteostasis in neuroendocrine cells. Molecular Metabolism 63:101542
*Greenwood MP, Greenwood M, López SB, Hawkins JW, Short K, Tatović D and Murphy D (2023)
Osmoadaptive GLP-1R signalling in hypothalamic neurones inhibits antidiuretic hormone synthesis and release. Mol Metab 70:101692
*Bárez-López S, Mecawi AS, Bryan N, Pauža AG, Duque VJ, Gillard BT, Murphy D and Greenwood MP (2023) Translational and post-translational dynamics in a model peptidergic system. Mol Cell Proteomics 22:100544