The Cellular Scale Program aims to employ advanced machine learning-based protein design to create high-affinity binding probes that identify and target key regulators of mitophagy in Alzheimer’s. It also seeks to develop iPSC-generated models to understand the interplay between the cytoskeleton, mitochondria, and energy in Alzheimer’s. Additionally, the program supports a biotech start-up’s vision to address autophagy-driven degradation and correct mitophagy in Alzheimer’s. By exploring the novel role of ICL-tribute in the onset or spread of Alzheimer’s hallmarks, the program aims to gain new insights. Furthermore, it will investigate whether aging and deprivation of glucose and oxygen in mice replicate the mitochondrial dysfunction observed in Alzheimer’s.

Projects:

– Designing bespoke protein binders for analysing mitochondrial disruption

– Cytoskeletal transformation leading to mitochondrial disruption

– Targeting mitophagy to protect neuronal health in Alzheimer’s disease

– Metabolic and molecular protection against mitochondrial genome damage

– Impact of mitochondrial transfer on Alzheimer’s disease hallmarks in iPSC-derived neurons

– Mitophers: A Novel Pathway for Ejecting Damaged Mitochondria from Neuronal Axons (MIND-AD CRE Funded; CI Zuryn, CI Iyer, CI Lazarou, AI Anggono)

– Understanding the C5a-C5aR-mitochondrial axis connecting neuroinflammation and neurodegeneration in Alzheimer’s disease (MIND-AD CRE Funded; AI Padmanabhan, CI Iyer, AI Anggono)

– Understanding neurodegeneration at a subcellular level: a multi-omic approach (MIND-AD CRE Funded; CI Vickers, Dr Andrew Phipps, Prof. Anna King, A/Prof. Anthony Cook, Dr. Bryony Thorne)

– Establishing CNS penetrance of a mitophagy inducing compound (MIND-AD CRE Funded; CI Lazarou, CI Nisbet, AI White)