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.

Investigator-led 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 (CI Zuryn, CI Iyer, CI Lazarou, AI Anggono)

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

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

– Establishing CNS penetrance of a mitophagy inducing compound (CI Lazarou, CI Nisbet, AI White)

– Binders to selectively assess how tau structural states impact cellular health and energy metabolism (AI Hatters, CI Nisbet, AI Shepherd, CI Collins)

– Multipronged neurotrophin delivery strategies to restore proteostasis and bioenergetics (CI Götz, AI Kretzmann, AI Killugudi Swaminatha Iyer, AI Padmanabhan, Dr. Gerhard Leinenga, Julia Brandt, Godfrey Njkajja)

– Investigating neuronal and glial mitochondrial dysfunction in tauopathies (CI Nisbet, AI Hatters, CI Lazarou, CI Ooi)

– Exploring the bidirectional relationship between protein aggregation and mitochondrial function in Alzheimer’s disease iPSC models (CI Ooi, CI Zuryn)

EMCR-led Projects

– Neuronal survival signalling in energy-stressed brain cells: A path to drug discovery (Dr. Jacinta Conroy, Dr. Michael Healy)

– Investigating early intervenable mitochondrial dysfunction associated with amyloid and tau pathology using high-throughput immunohistochemistry and human stell cell-derived excitatory neurons (Dr. Michelle Newbery, Dr. Kathryn Laloli, Dr. Neville Ng, Dr. Derya Dik, AI Shepherd, CI Ooi)