Summary
Both obesity and Alzheimer’s disease are characterized by increased neuroinflammation, with increasing evidence of the importance of the brain in the control of peripheral immune response.
Glucagon-like peptide-2 is a hormone secreted from intestinal L cells in response to nutrient intake. GLP2 improves the gastro-intestinal tract permeability and function in animal models and humans alike.
GLP2 receptors have been localized to multiple peripheral organs and the central nervous system, and its agonism has been shown to exert anti-inflammatory effects on the liver and brain.
Two distinct brain cell populations are thought to control the central and peripheral immune response; microglia and Dopamine beta-hydroxylase (Dbh) neurons.
Project aims
There are two aims in this project:
First, we will characterise Glp2r and Dbh expressing neurons in human and mouse, using our in-house spatiocellular Hypomap databases and publicly available single cell resources. We will study the transcriptomic and proteomic profiles of these neurons in states of obesity and Alzheimer’s disease, in both humans and rodent models, in order to identify new potential therapeutic targets.
Second, we will leverage human genetic data to investigate the effect of GLP2 signaling using a Mendelian randomization method. We will explore the genetic associations of GLP2 and GLP2R with obesity and other diverse inflammatory diseases outcomes.
We believe that a better understanding of the central immune response is a prerequisite for the development of new drugs to tackle both obesity and Alzheimer’s disease.
Contact details
Giles Yeo - gshy2@cam.ac.uk
Opportunities
This project is open to applicants who want to do a:
- PhD