Understanding the intricate parallelism between presynaptic autophagy and neuronal health

In less than 200 words, what main research questions are you working on? Please make sure to first include a brief context and background to your research, articulate your question(s) and conclude with why you think it’s important to study the them (i.e., the potential broader impacts).

Imagine an electrical circuit as a jumble of series and parallel connections and a wire goes bad. The result? Poofff!!! Our brain is housing an exactly similar ‘circuit’ and any of the ‘wires’ going ‘bad’ might land us into a similar ‘dark’ situation. We shall henceforth address the ‘wires’ as neurons. Neurons conduct electrical impulses in the form of action potentials. The neurotransmitters released from Neuron A can either help (excite) or hinder (inhibit) Neuron B from firing its action potential. Presynaptic terminals are the sites of neurotransmitter storage and release. Synaptic vesicles constantly fuse with the nerve terminal membrane, releasing the neurotransmitters and are recycled back for reuse. The synaptic vesicle cycle can occur at a rate of over 100 cycles/sec. The process requires the coordination between a large group of ‘presynaptic’ proteins. Proteostatic machineries (like autophagy) in synapses play an important role in determining the health of a neuron. Autophagy in the synapse is a highly regulated process that overall defines the proper functioning of neurons by clearing aggregates commonly encountered in neurodegenerative disorders, such as Alzheimer’s, Parkinson’s, ALS and Huntington. My goal is to understand the intricate parallelism between presynaptic autophagy and neuronal health using mice, Drosophila and C.elegans as model systems and alleviate the symptoms (rescue of phenotype) using chemical and genetic approaches.