BH3- Only Proteins and Cellular Bioenergetic in the Control of Neuronal Survival and Cell Death:
Role in Ischaemic Injury and Neurodegeneration
The programme investigates key mechanisms underlying neuronal survival and cell death in response to ischemic brain injury and during chronic neurodegeneration. It investigates the role of pro-apoptotic BH3 Only Proteins and cellular and mitochondrial bioenergetics in cell death and cell survival decisions in response to neuronal Ca2+ overloading, endoplasmic reticulum stress, and oxygen/glucose deprivation. These studies are conducted using established neuronal cell culture and organotypic slice culture systems, and key findings are translated into appropriate animal models. Building on our expertise and previous investments in single-cell analysis, quantitative microscopy, and computational biology, we also identify key decision and intervention points using both hypothesis-driven and systems-driven research approaches. These investigations will generate novel therapeutic targets and prognostic tools for drug discovery, which could ultimately benefit the treatment of ischemic brain injury, chronic neurodegeneration, and potentially other disorders of inappropriate cell death signalling.
This program has generated more than 55 publications and developed the computational models of Bcl-2 family interactions and MOMP regulation, mitochondrial respiration, and AMPK signalling relevant for the current application.
For more details see here.
This project is funded by SFI under the Principal Investigator Programme.