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Brief Profile of the Awardee

awardee

Dr Thomas Pucadyil

  • 2018
  • Biological Sciences
  • 20/11/1976
  • Membrane Biochemistry and Vesicular Transport
Award Citation:

Academic Qualifications:
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Thesis and Guide details:
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Details of CSIR Fellowship/ Associateship held, if any or from other sources/ agencies.
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Significant foreign assignments:
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(a) Significant contributions to science and/ or technology development by the nominee based on the work done in India during most part of last 5 years:
Generation of vesicles from a membrane compartment is fundamental to diverse cellular processes such as protein sorting and degradation, synaptic transmission and organelle biogenesis. Every vesicle that is formed in the cell is an outcome of membrane budding and fission; both of which requires the localized application of curvature stresses in order for a planar membrane to curve into a bud-like intermediate. The bud defines a neck, which undergoes further constriction to get severed from the parent membrane. Since these topological transformations require the membrane to deviate from its preferred planar configuration, budding and fission reactions are energetically unfavorable process. Cells have evolved protein machines that often utilize energy from nucleotide hydrolysis to catalyze this process. Dr. Pucadyil’s research efforts are directed towards understanding the diversity of and mechanisms by which such catalysts function. Tools for such analysis constitute direct reconstitution of membrane budding and fission on model membrane systems. Towards this, Dr. Pucadyil’s lab utilizes an indigenously developed elegant new assay system that combines a planar supported bilayer and an array of supported membrane nanotubes tubes prepared simply by flowing buffer over a dried lipid mix deposited on a passivated glass coverslip (Dar et al., 2017, Nat. Protocols). These templates can be prepared with as little as 1-2 nmol of lipids, and within minutes using a commercially available flow cell. Together, this assay enabled his group to establish for the first instance that membrane curvature itself can act as a powerful determinant to sort adaptors in the widely studied clathrin-mediated endocytic pathway (Holkar et al., 2015, J. Biol. Chem.). Furthermore, he demonstrated that adaptor-dependent clathrin assembly is dramatically favored on a curved than a planar membrane surface (Pucadyil and Holkar, 2016, Mol. Biol. Cell), suggesting therefore that clathrin likely captures and stabilizes a preformed membrane bud rather than inducing the formation of a membrane bud. The large GTPasedynamin represents a group of specialized protein machines that catalyze membrane fission. Membrane tubes represent an ideal mimic of the necks of clathrincoated pits, the physiological substrate for dynamin. Using the assay system described above, Dr. Pucadyil’s group demonstrated that the paradigmatic fission apparatus dynamin functions via a constriction-based mechanism to define a prefission intermediate of ~5 nm in radius (Dar et al., 2015, Nat. Cell Biol.). Recently, his group established that constriction is solely a function of structural rearrangements occurring in the GTPase and stalk domains of dynamin and that severing of the pre-constricted state is facilitated by the membrane-interacting pleckstrin-homology domain (Dar et al. 2017, Mol. Biol. Cell). In summary, Dr. Pucadyil’s novel findings provide a unified model to understand membrane fission. Furthermore, since the assay system is facile and can easily be set-up using commercially available reagents and apparatus, his work is destined to exert positive impact in the community in facilitating analysis of other fission reactions.
(b) Impact of the contributions in the field concerned:
Research in the Pucadyil laboratory focuses on understanding how cells produce vesicles that package and transport membrane proteins across various subcellular compartments. His lab currently focuses on the widely studied clathrin-mediated vesicular transport pathway. His research complements traditional cell biological assays with biochemical reconstitution approaches to recreate the pathway by which proteins induced membrane budding and fission. His lab is credited for developing an elegant model membrane assay system of a planar lipid bilayer connected to an array of highly curved membrane nanotubes. This unique membrane template mimics the topology of many cellular organelles and allows for the facile and dynamic analysis of membrane budding and fission reactions using fluorescence microscopy. Such technological development is as fundamental to the field of membrane biology as is the invention of the widely used 'liposomes' by Bangham and coworkers in the 60's. Using such assays, his lab's research on recreating the selfassembly process of the clathrin coat on membranes marks a paradigm shift in the field of vesicular transport as it indicates that membrane budding precedes the self-assembly of the clathrin coat. Furthermore, his lab's research has revealed the pathway to how clathrin-coated membrane buds are severed by the GTPasedynamin. Dr. Pucadyil joined IISER Pune in October 2010. In the span of eight years, research from his laboratory has made significant impact at the national and international levels, especially in the fields of vesicular transport. Dr. Pucadyil’s research has been published in some of the best journals in the field and has attracted a lot of attention from the vesicular transport community. Dr. Pucadyil’s lab focuses on two aspects of vesicular transport, namely how proteins induce budding of a planar membrane and how proteins catalyze fission of membrane buds to release vesicles. His group is specifically interested in the clathrin-mediated vesicular transport pathway that manages the sorting and internalization of the bulk of membrane proteins from the plasma membrane. Despite the early identification of participant proteins in this pathway and the large number of research groups working in this area, his lab was the first to directly visualize the dynamics of clathrin assembly on membranes in real time, which allowed analysis of specific determinants that facilitate this process. Clathrin is recruited to the membrane by its interaction with specific adaptors that bind membrane proteins and lipids. Conventionally, it is assumed that the self-assembly of clathrin into a basket-shaped polymer drives budding of the underlying membrane. Remarkably, in reactions involving a combination of purified adaptor proteins and clathrin added to the above described model membrane assay system, Dr. Pucadyil's group showed that the adaptor in fact sorts to regions of high membrane curvature, which in turn marks sites of clathrin self-assembly (Holkar et al., 2015, Journal of Biological Chemistry). The significance of this observation to the vesicular transport community is emphasized by the fact that this work was accepted for publication within a week and quickly made it to the 'most read' category of articles in the journal. Furthermore, his group showed that on a planar and curved membrane surface displaying equal density of adaptors, clathrin preferentially binds and selfassembles on the curved membrane surface (Pucadyil and Holkar, 2016, Molecular Biology of the Cell). Thus, contrary to the popular notion.
Places where work of last 5 years has been referred/ cited in Books, Reviews:
(i). Paper Cited
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(ii). Book Cited
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Names of the industries in which the technology (ies) has (have) been used :
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The achievements already been recognised by Awards by any learned body:
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The Awardee a fellow of the Indian National Science Academy/Indian Academy of Sciences/National Academy of Sciences/Others:
The Awardee delivered invited lecture(s) in India/abroad and/or chaired any scientific Internatiional Conference Symposium:
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List of Awardee's 10 most significant publications.
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List of Awardee's 5 most significant publications during the last 5 years
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List of Awardee's 5 most significant publications from out of work done in India during the last five years:
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Complete list of publications in standard refereed journals:
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Complete list of publications with foreign collaborators (indicating your status as author):
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List of papers published in Conferences /Symposia/ Seminars, etc:
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List of the most outstanding Technical Reports/ Review Articles:
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Statement regarding collaboration with scientists abroad:
List of Patents taken
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Total number of patents granted in last five years.
Details of Books published:
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Contact Details


  • IISER Pune
    Indian Institute of Science Education and Research Pune
    Dr. Homi Bhabha Road, Pashan
    Pune - 411008
    Maharashtra
  • pucadyil[at]iiserpune[dot]ac[dot]in
11 Dec 2018, http://ssbprize.gov.in/Content/Detail.aspx?AID=537