Research Faculty

Mini Jose Deepak

Ramalingaswami and IYBA Faculty Fellow

Phone : +91 80 2293 2518
E-Mail : mini[at]

Research Areas

Differentiation of neuronal processes into subtypes

Research Details

How do neurons differentiate?

Establishment of cell polarity plays a crucial role for development, motility and survival in all eukaryotic systems. Diffusion of biomolecules on the plasma membrane creates asymmetry, generating cell polarity. Lipid homeostasis plays a major role in creating this molecular asymmetry. My group focuses on addressing a fundamental, yet important question in neuroscience: How is cell polarity established during neuronal development or how do the neurons differentiate?

Differentiation of neuronal processes into subtypes namely, axons and dendrites, remain to be a highly intriguing but critical mechanism for survival during neuronal development. It plays a key role in establishing specialized neuronal processes to form cell-cell contacts or synapses, crucial for signal processing in the brain. Early in development, the short neuronal processes called neurites grow similar to each other in a symmetric manner. A sharp transition during the growth period allows one of the processes to grow at a much faster rate compared to the other processes, which develops as the axon. It has been found that there are molecular and structural differences between axons and the dendrites. Interestingly, though different approaches have been adopted to intercept the molecular mechanism behind, a clear model on this critical transition during development, which determines neuronal survival, remains to be understood.

Lipid metabolism has been shown to hold the key to major fundamental processes including neuronal differentiation. In my lab, we try to unravel the molecular mechanisms underlying neuronal polarity using a multidisciplinary approach combining molecular biology, genetic engineering, pharmacology, Optogenetics and multiple advanced microscopy paradigms including FRET, FLIM and single molecule based superresolution microscopy. A combination of state-of-the-art interdisciplinary paradigms is adopted to understand the collective spatiotemporal events resulting in complex neuronal structure and function using rodent hippocampal neurons as a model system.

Recent evidence from our lab is one of the first which signifies the stark effect of a transient alteration in membrane resulting in altered membrane viscosity and Brownian diffusion, thereby resulting in long term deficits in neurite outgrowth and polarity establishment (Jose et al, Front. Mol. Neur. 2021). Our study also emphasizes the importance of addressing this condition at an early developmental phase, when the deficits can be rescued by precise control of the membrane lipid balance. Thus, this study identified membrane cholesterol as a critical factor for axo-dendritic specification and a key molecule for determining neuronal architecture.

Combining optogenetics with super resolution microscopy, we showed how photoactivation controls the stochastic organization and lateral random movement of single molecules of HCN channels, crucial in regulating the membrane potential, in live cells by altering the intracellular cAMP levels (Tanwar et al, RSC Chem. Bio., 2021). This study shows one of the first paradigms combining these state-of-the-art techniques to alter the biochemical maps of ion channels in live cells. Our current studies focus on understanding the correlation of these pathways and their implication in multiple developmental and neurodegenerative disorders.


Belapurkar V., Swamy M.H.S, Singh, N., Kedia S., Gangi Setty S.R., Jose M., Nair D. , (2023), Real time heterogeneity of supramolecular assembly of Amyloid Precursor Protein is modulated by an endocytic risk factor PICALM., Cellular and Molecular Lifesciences, 80

Mangalwedhekar R., 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

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): 4236.

Jose M.*, Sivanand A., Channakeshava C., (2021), Cholesterol is a critical determinant for hippocampal neuronal polarity, Frontiers in Molecular Neuroscience, 14

Kedia S., Mandal K., Netrakanti P.R., Jose M., Sisodia S.S., Nair D., (2021), Nanoscale organization of Nicastrin, the Substrate Receptor of the γ-Secretase Complex, as Independent Molecular Domains, Molecular Brain, 14(1):158

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.

Kedia S., Ramakrishna P., Netrakanti P.R., Sisodia SS, Jose M., Kumar S, Mahadevan A, Ramanan N. Nadkarni S., Nair D., (2020), Alteration in synaptic nanoscale organization dictates amyloidogenic processing in Alzheimer’s disease, IScience, 24(1), 101924.

Kedia, S., Ramakrishna, P., Netrakanti, P. R., Jose, M., Sibarita, J. B., Nadkarni, S., & Nair, D., (2020), Real-time nanoscale organization of amyloid precursor protein, Nanoscale, 12(15), 8200-8215.

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

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

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

Sartorel E, Ünlü C, Jose M, Massoni-Laporte A, Meca J, Sibarita JB, McCusker D, (2018), Phosphatidylserine and GTPase activation control Cdc42 nanoclustering to counter dissipative diffusion, Molecular Biology of the Cell, 29(11), 1299-1310

Jose M., Tollis S., Nair D.K., Mitteau R, Velours C, Massoni-Laporte A, Rouyou A, Sibarita J.B., McCusker D, (2015), A quantitative imaging-based screen reveals the exocyst as a network hub connecting endocytosis and exocytosis, Mol Biol Cell, 26(13), 2519-2534

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

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, Biophys J, 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

Rajesh R. J., Jose M., and Bisht P. B, (2002), Diffraction efficiency of transient grating and relaxation profiles of some laser dyes, Ind. J. Physics, 76B:, 737-742