Project Reference: TRG27-IMS-CB1

Project title: Identifying mechanisms of adult brain plasticity for metabolic health

Project outline

The brain constantly adjusts how the body handles energy, signalling when to burn fuel, what type of energy substrate to use, and when to store energy. This project explores a surprising player in that control: oligodendrocytes, the brain cells best known for wrapping nerve fibres in an insulating sheath called myelin. Once thought to be fixed in adulthood, these cells are in fact continually replaced throughout life, a process called oligodendrogenesis. Building on our earlier discovery that oligodendrocytes in the hypothalamus, the brain's energy-control centre, are unusually dynamic, we now have pilot data suggesting that the birth of new oligodendrocytes in adults helps the body stay metabolically flexible: able to quickly adapt to transitions from periods of nutrient scarcity to nutrient excess

This studentship will test how adult oligodendrogenesis shapes normal metabolic physiology, asking three questions. When and where are new oligodendrocytes made as healthy mice experience short periods of too much or too little energy? Does increasing or decreasing their production change how the body uses and stores fuel? And what role does Adamts4, a protein that remodels the environment around brain cells, play in this plasticity?

To answer these, the student will use cutting-edge genetic tools that switch oligodendrocyte production on or off in specific brain regions, alongside a newly developed mouse lacking Adamts4 in adulthood. They will combine whole-body metabolic measurements, tracking which fuels are burned and stored, with brain imaging and molecular analysis of newly formed cells.

The project offers broad training in neuroscience, metabolism, mouse genetics, imaging and physiology, and aims to reveal a fundamental link between brain cell renewal and the everyday flexibility that keeps energy balance healthy.

Principal Supervisor

Professor Clemence Blouet

Email address: csb69@cam.ac.uk

Department / Partner Institute: Institute of Metabolic Science (IMS)

Website: https://www.blouetlab.org/

BBSRC strategic theme

Understanding the rules of life