Ajantha Abey

Postdoctoral Research Project

My postdoctoral research is part of a larger ASAP (Aligning Science Across Parkinson's)-funded project led by the Cragg Lab, aimed at understanding the role of cholinergic interneurons in regulating dopamine release in the striatum. Striatal dopamine is key for controlling movement and cognition, and dysregulation of this is a feature of Parkinson's disease.

While much of our understanding of cholinergic-dopamine neuron interactions in the striatum comes from animal models, my contribution to the project is to develop striatal cholinergic interneurons from human induced pluripotent stem cells (iPSCs), to be able to model these cells in the dish. Striatal cholinergic interneurons have never been generated from iPSCs before, so we are applying a combination of neurodevelopmental insights and brute force optimisation to discover how to create these cells from scratch.

We hope to understand what intrinsic dysfunction these cells might have in a Parkinson's disease genetic context, and coculture them with other neurons in our striatal circuit models (see Do et al. 2024) to see how they modulate dopamine release. This will open the door to a whole new avenue of therapeutic targets for Parkinson's disease, and unlock further opportunities in understanding the development and biology of the striatum.

DPhil Research Project

I first came to Oxford for my DPhil with the Wade-Martins lab in 2020 funded by a Clarendon Scholarship, focused on understanding selective neuronal vulnerability in Alzheimer's and Parkinson's disease. I used healthy and patient cell lines and differentiated these into both cortical and dopaminergic neurons - two cell types of contrasting vulnerabilities in these diseases. I exposed these cells to tau and alpha synuclein fibrils, and focused on developing an in vitro model of Lewy pathology in differentially vulnerable cells.

By examining lysosomal, mitochondrial, and calcium biology in these cells using high throughput live imaging, we discovered that autophagy function was a key determinant of cellular vulnerability to Lewy pathology, and the development of these Lewy aggregates was detrimental to the cells' neurite outgrowth. We are currently working on publishing this research which has been presented at conferences including ADPD, SCMND, and Tau Global.

The project was supervised by Professor Wade-Martins and Professor Colin Akerman, Dr. Nora Bengoa-Vergniory, with additional supervision from Dr Becky Carlyle. Eden Mellor-Davis also contributed to the project as part of an undergraduate internship.

Background

I am originally from Sydney, Australia, and did my undergraduate degree at the University of Sydney, completing a Bachelor of Science (Advanced) and Bachelor of Arts majoring in Neuroscience, Latin, and Ancient History. I also completed my Honours research in Anatomy and Histology with the Regenerative Neuroscience Group with Professor Michael Valenzuela and Dr Tom Duncan at the Brain and Mind Centre in 2018, and continued working with the group as a Research Assistant for the subsequent 2 years, before joining the Wade-Martins group.

In Sydney, my projects were examining tauopathy and synaptic loss in canine dementia as a model of human Alzheimer's disease. I showed that tauopathy in canine dementia matched the distribution patterns of pathology in human Alzheimer's disease (Abey et al. 2021), grounding these pet dogs as a promising translational model. The group also developed and trialled a novel stem cell therapy in these dogs, where I analysed behavioural and neuropathology data, showing remarkable remission in several animals (Valenzuela et al. 2022). As part of my work, I also developed differentiation protocols from scratch to generate functional neurons from these novel stem cells. 

Through this, I have developed a broad interest in ageing research, neuroscience, neurodegeneration, and regenerative/stem cell technologies.

Teaching and Other Activities

Besides research, I am also active in the department through various committees and teaching roles. I have an expertise in neuroanatomy and have been demonstrating undergraduate labs in this area and other aspects of neuroscience for eight years. I have also run tutorials on molecular mechanisms of cellular vulnerability in dementia and models of neurodegenerative disease for biomedical sciences students in the department and as part of the molecular mechanisms of neurodegenerative disease option. I have also hosted students for visiting projects, summer internships, and FHS projects.

While a DPhil student, I served as a student rep to the department and sat on the graduate studies committee and outreach committee. I now am part of the Alzheimer's Research UK ECR Committee, where we run scientific and outreach events, and I write blogs for Dementia Researcher.