A famous quote by a Spanish Neuroscientist, Santiago Ramón y Cajal: ‘As long as Brain is a mystery, the universe, the reflection of the structure of the brain will also be a mystery’ has always motivated me to learn and pursue neuroscience. We know, as humans, that we are clearly different and most of what makes us different is the Brain. Everything we remember, everything we feel, everything we do, everything we aspire to is basically the organ ‘Brain’. Numerous questions like, how precise connections are made at the synapses during development that lead to different cortical structures giving rise to cognitive and emotional circuitry; understanding fascinating processes like learning and memory formation, dream science, consciousness have always intrigued me.
Interdisciplinary research is the key for neuroscience. Neuroscience draws on insights and developments in disciplines as diverse as molecular biology, electronics, biomedical engineering, statistics, psychology, biophysics, pharmacology and linguistics.
One major aspect of neuroscience research is unraveling mysteries behind neuro-degenerative diseases. Let us first dive deep in understanding neuro-degenerative diseases like Alzheimer’s and Parkinson’s disorder and its relation to amyloid formation. Protein misfolding and the accumulation of amyloid aggregates are prominent features in a vast array of human diseases including numerous neuro-degenerative disorders. So what exactly is this amyloid aggregate or fibril? It is an insoluble, highly ordered aggregate of a protein and the major component of extracellular plaques found in an Alzheimer’s patient’s brain. Amyloid associated neuro-degenerative diseases occur via a mechanism that involves the abnormal folding and aggregation of specific disease associated proteins causing a toxic gain of function. Each neuro-degenerative disorder affects a specific subset of neurons even though the disease associated protein is often present in many cells throughout the brain and the rest of the body. The precise reason behind the aggregation of a disease protein and how exactly amyloid fibril formation takes place remains unclear.
My work involved understanding Alpha-Synuclein (a protein) aggregation in Parkinson’s disorder. Alpha-Synuclein is a presynaptic neuronal protein that is linked genetically and neuropathologically to Parkinson's disease. Oligomeric, fibrillar conformations or aggregates of alpha synuclein are the toxic species that mediate disruption of cellular homeostasis, synaptic function and neuronal death. The goal of all the experiments that I performed was to elucidate the exact mechanism of alpha synuclein fibril formation, to know exactly which amino acids of the alpha synuclein proteins are coming in contact (the folding configuration of the protein) as the protein forms oligomers and then fibrils and aggregates. All the aggregation reactions were performed in vitro (in a test tube or culture dish outside the living organism) and visualized using fluorescence spectroscopy and circular dichroism. I used and worked on very expensive equipment and machinery for the purpose of protein expression and purification (in vitro), to study and visualize protein aggregation kinetics, protein monomer and protein fibrillar structure.
Many research groups around the world are working on amyloidosis , intrinsically disordered proteins that are responsible for various neurodegenerative disorders but most of the translational and clinical research in this aspect is yet to be done.
I worked under the supervision of Dr. Samrat Mukhopadhyay at the Department of Biological Sciences, IISER Mohali.
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