Department of Biological Sciences
National University of Singapore
14 Science Drive 4
Ph.D. Baylor College of Medicine
M.Sc. National University of Singapore
B.Sc. National University of Singapore
National Research Foundation Fellowship 2015-2020
Parkinson’s disease and aging
Parkinson’s disease (PD) is a debilitating neurological movement disorder. Except in rare familial form of the disease, PD tends to affect older individuals, and the disease progresses with age. Heterogeneity of PD suggests complex interactions between genes, environment and the aging process.
Why use short-living model organisms?
A key risk factor of PD is aging. Hence, a good experimental model has to undergo aging to reveal PD-like phenotypes. Since any rigorous research require iterative testing of hypotheses or ideas for reproducibility and refinement of mechanistic understanding, organisms with short lifespans will allow such iterations to be executed in a robust manner. The organisms we use are the fruitfly, Drosophila melanogaster and the African turqouise killifish, Nothobranchius furzeri, which live maximum lifespans of 3 and 6 months, respectively.
How does alpha-synuclein contribute to PD?
SNCA is a key gene underlying PD. SNCA encodes the alpha-synuclein protein, which are found in aggregates called Lewy Bodies in PD post-mortem brains. We and others have hypothesized that diverse genetic and cellular interactions between SNCA and different genes may partly explain the heterogeneity of PD symptoms. We are currently studying such interactions in the fruitfly and the African turqouise killifish.
By performing a genetic screen in the fruitfly, we have identified tens of genetic interactors of alpha-synuclein. Currently, we are studying these genetic interactions using multiple approaches, including (A) optical imaging of dopaminergic neuron activity, (B) electron microscopy and electrophysiology.
During our investigations on the killifish brains (C), we have discovered synuclein-immunoreactive punctate structures in aging brains (D). Notably, no genetic modification was needed to induce these punctate structures. We believe that investigations in the aging killifish nervous system is likely to yield insights into a natural progression of synuclein-related pathology during aging.
Interested students and prospective postdocs please see our webpage at ktwlab.info.