OUR RESEARCH

The Molecular Scale Program aims to explore whether targeting specific regulators can simultaneously enhance mitochondrial function and suppress Tau aggregation. It adopts a proteomic approach to map the differential vulnerability of the neuronal proteome to misfolding and aggregation following energy stress or the expression of proteins with familial Alzheimer’s mutations. Additionally, the program seeks to provide the first description of the role of wild-type and pathological Tau in controlling NMDR trafficking in synaptic plasticity, offering a mechanistic basis for Tau-based therapeutic development. By applying machine-learning approaches to Alzheimer’s patient-derived neurons, the program aims to determine the mitochondrial components that drive Alzheimer’s pathogenesis. Furthermore, it will pre-clinically test combination therapies targeting signalling pathways involved in protein aggregation in Alzheimer’s.

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.

The Drug Targeting and Delivery Across Scales Program aims to deliver antibody therapeutics across the blood-brain barrier using adeno-associated virus to target Aβ and Tau pathology. It seeks to develop mRNA therapeutics for various intracellular targets, including Tau. Additionally, the program pioneers the world’s first intravenous targeted non-viral CRISPR therapy by utilising scanning ultrasound for genome editing in the brain. Furthermore, it focuses on delivering novel anti-Tau antibodies, with and without ultrasound, to enhance functional outcomes.