Perinatal asphyxia is a critical condition that occurs when there is a lack of oxygen supply to the foetus or newborn during the perinatal period. It can lead to severe neurological complications caused by impaired myelination and epileptogenesis. Understanding the mechanisms underlying this pathology is crucial for developing targeted therapeutic strategies.
We have evidence that oligodendrocytes, which are the cells that generate myelin to speed nerve conduction in the brain, express TRP channels that (1) become overactivated during ischaemia (Hamilton et al., Nature, 2016); (2) cause demyelination (Giacco et al., Glia, 2023); and (3) increase seizure propensity (Giacco et al., unpublished).
This PhD project aims to use a range of cutting-edge techniques to investigate this mechanism in rodent models of perinatal asphyxia and human tissue obtained from elective terminations and surgeries. The latter provides a unique translational aspect to the project. Specifically, the student will:
•Obtain a Home Office Personal Licence to generate a rodent model of perinatal asphyxia:
measure O2 concentrations in vivo (in collaboration with Catherine Hall at Sussex Uni).
• Learn patch-clamping, electron microscopy, western blotting, compound action potential recording and immunohistochemistry (IHC) to study cell function and cell death occurring in vivo during and after asphyxia.
• Set up experiments to study human foetal and paediatric tissue with patch-clamping, culturing and IHC techniques.
• Investigate the mechanisms leading to cell death during oxygen and glucose deprivation in organotypic slice experiments made from rodent and human tissue.
• Test whether block of candidate pathological pathways prevents OPC and myelin damage and promotes remyelination in vivo and ex vivo.
The Ahmed (MB/PhD, MA (Cantab), FRCS (SN)) and Hamilton-Whitaker Labs have a great track record of generating high-impact results and publications, and in training PhD students and would provide the support and platform needed to obtain the PhD.