Biology

Dr. Souvik Modi
University College London, UK

A major hallmark of a eukaryotic cell is compartmentalization of the cytoplasmic materials in the form of organelles. This compartmentalization has allowed cells to confine various small molecules and proteins and release them during spatial and temporal demand. Morphology, membrane contacts and ionic environment of these organelles are tightly regulated and often altered during pathological conditions. To understand this alteration in ionic heterogeneity, membrane contacts, and dynamics, one needs to develop novel sensors with high precision and sensitivity. Over the years my research mainly focused on the development of several nanoprobes using DNA or recombinant antibodies and their application in cell biology and neuroscience. I showed that DNA can be used to design an autonomous nanomachine that can act as a pH sensor inside living cells. This pH sensor is easily tuneable and can be targeted to subcellular compartments by a recombinant antibody acting as an adapter at the plasma membrane. Extending my interest in Nano sensors and recombinant antibodies, I then created a small and highly specific Quantum Dot conjugated nanoprobe functionalized with a nanobody against the Green Fluorescent Protein. This QD-nanobody conjugate was further used to explore the diffusion of adhesion molecules on growth cones and neurotransmitter receptors at synapses in vivo. This nanoprobe is specific to GFP and later used to explore nanocluster formation of a mitochondrial outer membrane protein Miro. I found these Miro clusters are important for mitochondrial and ER morphology and function. Miro knock out cells and neurons showed reduced trafficking and ER-Mitochondria contact sites which possibly resulted in neurodegeneration.