Faculty

Deepak Nair

Associate Professor

Phone : +91 80 2293 3535
E-Mail : deepak[at]iisc.ac.in
web: https://cns.iisc.ac.in/deepak/

Research Areas

Role of Dynamic Nanoscale Molecular Organization in the Signal processing at the Synapse

Research Details

Synapses, basic functional units of brain, are involved in the modulation of information flow between neurons. How synapses moderate this flow of information is key to functioning of the brain. Synapses control the transmission of information by differential recruitment, recycling and positioning of molecular components of the synapses. Our approach is to study the organization and dynamics of key synaptic molecules using a variety of interdisciplinary approaches. We aim to develop cutting edge microscopy and optogenetic tools to observe synapses at the nanoscale and real-time.

In the Central Nervous System (CNS), synapses form the basic functional units of connectivity between two neurons. The formation, remodeling and elimination of synapses refine the microcircuitry in the brain. Synapse is a complex molecular machine, which changes its structure and composition during neuronal development and plasticity. Synapse contains hundreds of proteins choreographed in to a micron sized machine overseeing the fidelity of brain function. The components of the synapses play a major role in synaptic transmission and synaptic plasticity, which are thought to underlie learning and memory. Interestingly most of the diseases has a direct impact on the number, position and trafficking of molecules in and out of synapse contributing towards synaptic loss or dysfunction thus affecting the normal behavior of the brain. However, it has been enigma how the information is processed at a single synapse by controlling function, position and regulation of several molecules.

This is partly because of the inaccessibility to garner information to resolve structures less than few 100nm. The development of super-resolution imaging methods (Nobel Prize Chemistry 2014) that break the diffraction limit allows monitoring the synaptic organization at the nanoscale (10-50nm). Super resolution imaging provides evidences that synapse functions by local regulation and organization of nanometer sized protein domains.

fig1

The work in our lab attempt to dissect the fundamental role of dynamic nanoscale organization of synaptic molecules in how synapse process and relay information. To achieve this we follow an interdisciplinary research paradigm at the interface of high end microscopy, molecular biology and cellular neuroscience.
In order to comprehend the role of spatial heterogeneity in synapses, it is important to determine structural organization of molecular components of nano sized protein domains. Super-resolution imaging based on single molecule based techniques (STORM, PALM) will be used to observe the real-time organization of these sub-synaptic complexes in live cells at 10-50nm. The outcome is expected to provide a structural basis for nanoscale organization in synaptic transmission.

It has been shown that the synaptic morphology can affect synapse stability and function. How modifications in dendritic morphology direct nanoarchitecture of synapse will be vital in decoding the role of molecular organization and mobility in synaptic strength. Concurrently, how synapse decides that it needs more or less molecules in the postsynapse in response to presynaptic stimuli is still unclear. Optogenetic approaches, neurotransmitter uncaging, single molecule diffusion studies and super resolution imaging will be combined at the level of single synapses to address the role of mobility and localization in synaptic retention of molecules at resolution of few 10nms at millisecond timescale in live cells during synaptic plasticity.

Another important aspect is to compare the basic synaptic organization in transgenic mice models for neurodegenerative diseases to see how the spatio-temporal properties of the molecules are affected. In this case focus will be laid on the organization and recruitment of some of the key molecules implicated in these diseases. With all these information, we intend to create an in-silico model to demonstrate the role of nanoorganization of molecules in health and disease.

fig2

Publications

Yuko Fukata, Masaki Fukata, Harold D MacGillavry, Deepak Nair, Eric Hosy, (2024), Celebrating the Birthday of AMPA Receptor Nanodomains: Illuminating the Nanoscale Organization of Excitatory Synapses with 10 Nanocandles, Journal of Neuroscience , 44 (23)

Sarmistha Mahanty, Ptissam Bergam, Vivek Belapurkar, Litralson Eluvathingal, Nikita Gupta, Bruno Goud, Deepak Nair, Graça Raposo, Subba Rao Gangi Setty, (2024), Biogenesis of specialized lysosomes in differentiated keratinocytes relies on close apposition with the Golgi apparatus, Cell Death & Disease, 15 (7), 496

Thumu S. C. R., Jain M., Soman S., Das S., Verma V., Nandi A., Gutmann D. H., Jayaprakash B., Nair D., Clement J. P., Marathe S., Ramanan S., (2024), SRF-deficient astrocytes provide neuroprotection in mouse models of excitotoxicity and neurodegeneration, eLife, 13:e95577, 1-28

Belapurkar, V., Singh, .N., Mahadevaswamy H.S., Subba Rao G.S, Kedia, S., Jose M., and Nair., D. , (2023), Real-time heterogeneity of supramolecular assembly of amyloid precursor protein is modulated by an endocytic risk factor PICALM, Cellular and Molecular Life Sciences, 80(10)

Haukedal, H.; Corsi, GI.; Gadekar, VP.;Doncheva, NT.; Kedia, S.; de Haan, N.; Chandrasekaran, A.;Jensen, P.; Schiønning, P.; Vallin, S.; Marlet, FR.; Poon, A.; Pires, C.; Agha, FK.; Wandall, HH.; Cirera, S.; Simonsen, AH.; Nielsen, TT.; Nielsen, JE.; Hyttel, P.; Muddashetty, R.; Aldana, B.; Gorodkin, J.; Nair, D.; Meyer, M.; Larsen, MR.; Freude, K., (2023), Golgi fragmentation – One of the earliest organelle phenotypes in Alzheimer’s disease neurons, Frontiers in Neuroscience, 17

Mangalwedhekar, M., Singh, N., Thakur, C.S., Seelamantula, C.S., Jose, M., Nair, D., (2023), Achieving nanoscale precision using Neuromorphic localization microscopy, Nature Nanotechnology, 18(4), 380-389

D’Souza, N., Ramakrishna, S., Radhakrishna, .K., Jhaveri, V., Ravindran, S., Yeramala, L., Nair, D.,Palakodeti, D., Muddashetty, R.S, (2022), Function of FMRP domains in regulating distinct roles of neuronal protein synthesis, Molecular Neurobiology, 59(12), 7370-7392

SG Dastidar, D Nair , (2022), A Ribosomal Perspective on Neuronal Local Protein Synthesis, Frontiers in Molecular Neuroscience, 18

AP Kumar, N Singh, D Nair, A Justin, (2022), Neuronal PET tracers for Alzheimer’s disease, Biochemical and Biophysical Research Communications , 587, 58-62

Rajeev P., Singh N., Kechkar A., Butler C., Ramanan N., Sibarita J.B., Jose M., Nair D., (2022), Nanoscale regulation of Ca2+ dependent phase transitions and real-time dynamics of SAP97/hDLG., Nature Communications , 13(1)

S Kedia, K Mandal, PR Netrakanti, M Jose, SS Sisodia, and D Nair , (2021), Nanoscale organization of Nicastrin, the substrate receptor of the γ-secretase complex, as independent molecular domains, Molecular Brain, 14(1)

Kedia, S., Ramanan, N., Nair, D., (2021), Quantifying molecular aggregation by super resolution microscopy within an excitatory synapse from mouse hippocampal neurons, STAR protocols, 2 (2)

Lankipalli, S., Mahadeva Swamy, H.S., Selvam, D., Samanta, D., Nair, D.,Ramgopal, U. , (2021), Cryptic association of B7-2 molecules and its implication for clustering, Protein Science., 30(9), 1958-1973

Mandal,P., Belapurkar, V., Nair, D Ramanan, N., (2021), Vinculin-mediated axon growth requires interaction with actin but not talin in mouse neocortical neurons, Cellular and Molecular Life Sciences online, 78, 5807-5826

Tanwar,M., Kateriya,S., Nair, D., Jose,M., (2021), Optogenetic modulation of real-time nanoscale dynamics of HCN channels using photoactivated adenylyl cyclases, RSC Chemical Biology, 2(3), 863-875

Nair, D., Kedia, S., Jose,M., (2021), Does altered probability of real-time diffussional collissions of membrane molecules trigger or delay Alzheimer’s Disease, iScience Notes, 5(3), 2020.

Kedia, S., Ramakrishna, P., Netrakanti, P.R., Singh, N., Sisodia, S.S., Jose, M., Sathish Kumar, Mahadevan, A., Ramanan, N., Nadkarni, S., and Nair, D., (2021), Alteration in synaptic nanoscale organization dictates amyloidogenic processing in Alzheimer’s disease, iScience, , 24(3)

Venkatesan, S., and Nair, D. , (2020), New Immunostaining Analysis Reveals Spatial and Molecular Variability in Synaptic Scaling, Neuroonline

Kedia, S., and Nair, D., (2020), Nanoscale rearrangement of APP organization as a therapeutic target for Alzheimer’s disease, Medical Hypotheses, 143

Marathe, P., Mahadeva Swamy, H.S., Nair, D, Bhattacharya, D., (2020), mEosBrite are bright variants of mEos3.2 developed by semirational protein engineering, Journal of Fluorescence, 30(3), 703–715.

Venkatesan, S., Subramaniam, S., Rajeev, P., Chopra, Y., Jose, M., and Nair, D., (2020), Differential scaling of synaptic molecules within functional zones of an excitatory synapse during homeostatic plasticity, eNeuro, 7(2).

Kedia, S., Ramakrishna, P., Netrakanti, P.R., Jose, M., Sibarita, J.-B., Nadkarni, S., and Nair, D., (2020), Real-time Nanoscale Organization of Amyloid Precursor Protein, Nanoscale, 12(15), 8200-8215.

Koltun, B., Ironi, S., Gershoni-Emek, N., Barrera, I., Hleihil, M., Nanguneri, S., Sasmal, R., Agasti, S.S., Nair, D., and Rosenblum, K., (2020), Measuring mRNA translation in neuronal processes and somata by tRNA-FRET, Nucleic Acids Research, 48(6), e32

Venkatachalapathy, M., Belapurkar, V., Jose, M., Gautier, A., and Nair, D. , (2019), Live cell super resolution imaging by radial fluctuations using fluorogen binding tags, Nanoscale, 11(8), 3626-3632.

Nanguneri, S., Pramod, R., Efimova, N., Das, D., Jose, M., Svitkina, T., and Nair, D., (2019), Characterization of nanoscale organization of F-actin in morphologically distinct dendritic spines in vitro using supervised learning, eNeuro, 6(4).

Kommaddi, R.P., Tomar, D.S., Karunakaran, S., Bapat, D., Nanguneri, S., Ray, A., Schneider, B.L., Nair, D., and Ravindranath, V., (2019), Glutaredoxin1 Diminishes Amyloid Beta-Mediated Oxidation of F-Actin and Reverses Cognitive Deficits in an Alzheimer’s Disease Mouse Model, Antioxidants & Redox Signaling, 31(18), 1321-1338.

Kommaddi, R.P., Das, D., Karunakaran, S., Nanguneri, S., Bapat, D., Ray, A., Shaw, E., Bennett, D.A., Nair, D., and Ravindranath, V. , (2018), Aβ mediates F-actin disassembly in dendritic spines leading to cognitive deficits in Alzheimer’s disease, Journal of Neuroscience, 38(5), 1085-1099.

Harper, C.B., Papadopulos, A., Martin, S., Matthews, D.R., Morgan, G.P., Nguyen, T.H., Wang, T., Nair, D., Choquet, D., and Meunier, F.A. , (2016), Botulinum neurotoxin type-A enters a non-recycling pool of synaptic vesicles, Scientific reports, 6(1)

Widera, D., Klenke, C., Nair, D., Heidbreder, M., Malkusch, S., Sibarita, J.-B., Choquet, D., Kaltschmidt, B., Heilemann, M., and Kaltschmidt, C., (2016), Single-particle tracking uncovers dynamics of glutamate-induced retrograde transport of NF-κB p65 in living neurons, Neurophotonics, 3(4)

Jose, M., Tollis, S., Nair, D., Mitteau, R., Velours, C., Massoni-Laporte, A., Royou, A., Sibarita, J.-B., and McCusker, D., (2015), A quantitative imaging-based screen reveals the exocyst as a network hub connecting endocytosis and exocytosis, Molecular biology of the cell, 26, 2519-2534.

Chazeau, A., Mehidi, A., Nair, D., Gautier, J.J., Leduc, C., Chamma, I., Kage, F., Kechkar, A., Thoumine, O., and Rottner, K. , (2014), Nanoscale segregation of actin nucleation and elongation factors determines dendritic spine protrusion, The EMBO journal, 33(23), 2745-2764.

Fraisier, V., Kasri, A., Miserey-Lenkei, S., Sibarita, J.-B., Nair, D., Mayeux, A., Bardin, S., Toyoda, Y., Poser, I., and Poznyakovskiy, A. , (2013), C11ORF24 is a novel type I membrane protein that cycles between the Golgi apparatus and the plasma membrane in Rab6-positive vesicles, PloS one, 8(12)

Nair, D., Hosy, E., Petersen, J.D., Constals, A., Giannone, G., Choquet, D., and Sibarita, J.-B., (2013), Super-resolution imaging reveals that AMPA receptors inside synapses are dynamically organized in nanodomains regulated by PSD95, Journal of Neuroscience, 33(32), 13204-13224.

Kechkar, A., Nair, D., Heilemann, M., Choquet, D., and Sibarita, J.-B., (2013), Real-time analysis and visualization for single-molecule based super-resolution microscopy, PLoS One, 8(4)

Jose, M., Tollis, S., Nair, D., Sibarita, J.-B., and McCusker, D., (2013), Robust polarity establishment occurs via an endocytosis-based cortical corralling mechanism, Journal of Cell Biology, 200(4), 407- 418.

Rossier, O., Octeau, V., Sibarita, J.-B., Leduc, C., Tessier, B., Nair, D., Gatterdam, V., Destaing, O., Albiges-Rizo, C., and Tampé, R., (2012), Integrins β 1 and β 3 exhibit distinct dynamic nanoscale organizations inside focal adhesions, Nature cell biology, 14(10), 1057-1067.

Hoze, N., Nair, D., Hosy, E., Sieben, C., Manley, S., Herrmann, A., Sibarita, J.-B., Choquet, D., and Holcman, D., (2012), Heterogeneity of AMPA receptor trafficking and molecular interactions revealed by superresolution analysis of live cell imaging, Proceedings of the National Academy of Sciences, 109(42), 17052-17057.

Heidbreder, M., Zander, C., Malkusch, S., Widera, D., Kaltschmidt, B., Kaltschmidt, C., Nair, D., Choquet, D., Sibarita, J.-B., and Heilemann, M. , (2012), TNF-α influences the lateral dynamics of TNF receptor I in living cells, Biochimica et Biophysica Acta (BBA)-Molecular Cell Research, 1823(10), 1984-1989.

Izeddin, I., Boulanger, J., Racine, V., Specht, C.G., Kechkar, A., Nair, D., Triller, A., Choquet, D., Dahan, M., and Sibarita, J.B., (2012), Wavelet analysis for single molecule localization microscopy, Opt Express, 20(3), 2081-2095.

Jose, M., Nair, D.K., Altrock, W.D., Dresbach, T., Gundelfinger, E.D., and Zuschratter, W., (2008), Investigating interactions mediated by the presynaptic protein bassoon in living cells by Foerster’s resonance energy transfer and fluorescence lifetime imaging microscopy, Biophysical journal, 94(4), 1483-1496.

Jose, M., Nair, D.K., Reissner, C., Hartig, R., and Zuschratter, W., (2007), Photophysics of Clomeleon by FLIM: discriminating excited state reactions along neuronal development, Biophysical journal, 92(6), 2237-2254.

Nair, D.K., Jose, M., Kuner, T., Zuschratter, W., and Hartig, R., (2006), FRET-FLIM at nanometer spectral resolution from living cells, Optics express, 14(25), 12217-12229.