PhD Glial regulation of neural pathways controlling nutrient sensing

Closing Date

23 Nov 2018

Salary

£14,777

Address

Medical School, University of Exeter

Duration

3.5 years

Project Description

Supervisory team: 
Dr Kate Ellacott, University of Exeter Medical School 
Dr Craig Beall, University of Exeter Medical School 
Professor Tony Pickering, University of Bristol 
Professor Andy Randall, University of Exeter Medical School 

Project description: 
Dysfunctional control of blood glucose levels leads to diabetes. This project explores hindbrain circuitry controlling blood glucose, focusing on the contribution of astrocytes. You will advance understanding of nutrient sensing by astrocytes and how manipulation of these cells alters neuronal excitability to impact blood glucose control.  

Having sufficient energy to fuel life is essential for survival; thus, understanding the basic biological mechanisms underlying the regulation of energy availability is important for human and animal health. The brain controls energy availability, regulating food intake and blood glucose levels by integrating information transmitted via hormonal, nutrient and direct nervous inputs from the rest of the body. Improving our understanding of how energy availability is regulated will help inform the development of treatments for increasingly prevalent debilitating conditions in which these systems are disrupted, including obesity, diabetes, anorexia and disease-associated cachexia. 

Astrocytes are a major class of glial cell in the CNS. Originally thought to be “housekeeping” cells in the brain, dynamic changes in astrocyte activity are increasingly being recognised for their role in mediating a range of physiological processes, in part by modulating communication between neurons. Within the brain, astrocytes in the hypothalamus can modulate food intake, but our current understanding of how astrocytes in other relevant brain regions, such as the dorsal vagal-complex (DVC), respond to nutritional changes and thereby impact neuronal circuitry regulating energy availability is limited. The DVC is bidirectionally connected, via the vagus nerve, to the digestive tract and is responsive to changes in energy availability, including blood glucose levels, so represents a key regulatory node between the brain and the rest of the body. 

Building on ongoing work from our collaborative research team, this studentship will explore how astrocytes in the DVC regulate neural circuits controlling blood glucose. Using state of the art technologies including chemogenetics and 2-photon microscopy, the student will explore how astrocytes sense changes in energy availability and how, in turn, experimental manipulation of astrocyte function can alter neuronal excitability and impact blood glucose levels. This will be investigated under normal conditions and when these pathways are impacted by obesity. These questions will be explored using the mouse as an experimental model. The student will utilise virally-mediated transgenic modulation of astrocyte signalling followed by characterization of changes in physiology in the living animal. This will be combined with training in 2-photon imaging, electrophysiology, histology, and molecular biology, which will be utilised to investigate the underlying molecular mechanisms. 

This studentship provides outstanding opportunities for training in an exciting area of neuroscience at the interface between physiology, endocrinology and pathology. The student will join a research team with a proven track record of collaboration and will have access to the joint expertise, resources, and facilities of the Universities of Exeter and Bristol. 

To apply for this project please complete the application form at https://cardiff.onlinesurveys.ac.uk/gw4-biomed-mrc-dtp-student-2019 by 5pm Friday 23 November 2018. 
 

Funding Notes

This studentship is funded through GW4 BioMed MRC Doctoral Training Partnership. It consists of full UK/EU tuition fees, as well as a Doctoral Stipend matching UK Research Council National Minimum (£14,777 for 2018/19, updated each year) for 3.5 years. 

For further information relating to the funding click here