DBT-Ramalingaswami Fellow, Structural biology of therapeutic targets
Research Focus Key Words:
Structure-function studies of therapeutic targets, protein-protein complexes, infectious disease biology, X-ray Crystallography, Cryo-EM, SAXS.
Dr. Urvashi Sharma graduated with a master’s degree in Biochemistry from Devi Ahilya Viswavidyalaya (DAVV), Indore. She persuaded her PhD in structural biology and biochemistry from CSIR-National Chemical Laboratory (NCL), PUNE under supervision of Prof. Dr. C. G. Suresh, where she deciphered the crystal structures of plant lectins recognizing complex sugars using X-ray crystallography. Later she secured postdoctoral position in collaborative team of Drs Nushin Aghajari and David JS Hulmes, at CNRS-Institute of biology and chemistry of proteins (IBCP) Lyon, France. Along with colleagues at IBCP, she investigated into the structural mechanisms of procollagen chain trimerization and regulation of procollagen processing. She moved to Vlaams Instituut voor Biotechnologie (VIB)/UGhent, Belgium in the Advance live cell imaging group of Prof. Daniel VanDamme to contribute into structural characterization of novel hetero-hexameric Tplate complex of plants (850 kDa) playing key role in Clathrin mediated endocytosis by using a combination of Cryo-EM/X-ray crystallography methods.
Dr Sharma’s latest postdoctoral work into Prof Ravi Acharya’s group at University of BATH, UK included Neprilysin-inhibitor binding studies in order to design safer drugs to treat hypertension/Cardiovascular diseases (CVDs).
“Dr. Sharma has joined IBAB in July 2020 as a DBT-Ramalingaswami fellow to initiate target validation of some of the novel Glycosyl transferases (GTs) of Mycobacterium tuberculosis.
PhD: CSIR-National Chemical Laboratory (NCL), PUNE, INDIA.
CNRS-Institute of Biology and Chemistry of proteins (IBCP) Lyon, France.
Vlaams Instituut voor Biotechnologie (VIB), Plant systems biology (PSB)/UGhent, Ghent, Belgium.
Department of Biochemistry, University of BATH, UK.
Department of Physical Chemistry, Oklahoma State University (OSU), Stillwater, OK, USA.
Guest Faculty, Department of Studies and Research in Biochemistry, Tumkur University, Karnataka.
- Validation of novel Glycosyl transferases (GTs) in Mycobacterium tuberculosis (M.tb) Cell wall biosynthesis:
Mycobacterium tuberculosis (M.tb.) is a virulent pathogen causing tuberculosis, a disease responsible for millions of deaths worldwide. Most of the first-line tuberculosis (TB) drugs are targeted against cell wall synthesis; however, the complete inhibitory mechanism remains unresolved. In addition, the emergence of multidrug resistance (MDR) is a serious threat. With the funding support from DBT, Govt of India, in my lab here at IBAB we have initiated structural studies of novel GTs of Mycobacterium tuberculosis (M.tb.) which are unique to the bug and appears to be high confidence drug targets. We will be employing classical tools in biochemistry and biophysics for protein engineering and characterization including SAXS, X-ray crystallography.
- Understanding the diverse roles of zinc-metallopeptidases in human health and disease.
Research interests in my team also includes studies on members of metzincin family of human zinc-metallopeptidases which are directly implicated in regulation of key physiological processes such as in maturation of fibrillar collagens and several components of extracellular matrix (ECM). Bone morphogenetic protein-1 (BMP1) being the key protease in collagen maturation has been an attractive target to develop a drug against Fibrosis disease which effects several tissues types such as liver, lungs, kidney and heart. In association with teams of CNRS-Institute of Biology and Chemistry of Proteins (IBCP, Lyon, France) we have identified a novel potent inhibitor protein from Xenopus which has given an unprecedented insight to design specific small molecules inhibitors of human BMP1. While some other therapeutically important zinc-endopeptidases are key targets for treating hypertension and Cardiovascular diseases (CVDs), also implicated for degradation of beta amyloid (βA) peptides are subjects of future investigations in our team.
- Dr Nushin Aghajari, Molecular Microbiology and Structural Biochemistry, CNRS- Institute of biology and chemistry of proteins (IBCP)/UMR5086-University of Lyon, LYON, France.
- Drs Catherine Moali and Sandrine Vadon-le Goff, Tissue Biology and Therapeutic Engineering Laboratory, CNRS-Institute of biology and chemistry of proteins (IBCP)/UMR 5305, LYON, France.
(* as equal contributors)
- Sharma U*, Cozier G, Sturrock ED, Acharya KR.
Molecular Basis for Omapatrilat and Sampatrilat Binding to Neprilysin Implications for Dual Inhibitor Design with Angiotensin-Converting Enzyme.
J. Med. Chem. 63, 10, 5488−5500, April 27, 2020 https://doi.org/10.1021/acs.jmedchem.0c00441.
- Pulido D, Sharma U, Vadon-LeGoff S, Hussein S-A, Cordes S, Bettler E, Moali C, Aghajari N, Hohenester E & Hulmes DJS.
Structural basis for the acceleration of procollagen processing by procollagen C-proteinase enhancer-1.
Structure, Jul 12 (2018), pii: S0969-2126(18)30243-0. doi: 10.1016/j.str.2018.06.011.
- Sharma U*, Carrique L, Vadon-LeGoff S, Mariano N, Georges RN, Delolme F, Karpinnen P, Myllyharju J, Moali C, Aghajari N, Hulmes DJS.
Structural basis of homo- and hetero-trimerization of collagen I.
Nature communications, 8:14671(2017), doi: 10.1038/ncomms14671.
- Sharma U, Katre UV and Suresh CG.
Crystal structure of a plant albumin from Cicer arietinum (chickpea) possessing hemopexin fold and hemagglutination activity.
Planta, 241, 1061–1073, (2015), DOI 10.1007/s00425-014-2236-6.
- Sharma U, Gaikwad SM, Suresh CG, Dhuna V, Singh J, Kamboj SS.
Conformational Transitions in Arisaema curvatum Lectin: Characterization of an Acid Induced Active Molten Globule.
Journal of Fluorescence, 2, (2011), 753-763.
- Sharma U & Suresh CG.
Purification, crystallization and X-ray characterization of a trypsin inhibitor protein from the seeds of chickpea (Cicer arietinum).
Acta Cryst. F67 (2011), 714-717.
Invited speaker in conferences
- The South West Structural Biology Consortium (SWSBC), 11-12 July 2019, University of Reading, UK.
- Good memories session: 1-day conference on “Collagen in all its forms”. 09, November 2018, ENS, LYON, FRANCE.
- BSMB meeting: Building the Extracellular Matrix: Molecules, Cells and Evolution, 7-8 April 2014, Bristol, UK.
Ramalingaswami Re-entry Fellowship/research Grant (2019-2023), Department of Biotechnology (DBT), Government of India (Ongoing).
European INSTRUCT GRANT (PID-2876), September 2017, in the group of Prof Van Damme, VIB, Belgium to access the IGBMC-Instruct Platform, Strasbourg, France (completed).
BIOCARE-women scientist grant (Dec 2016), Department of Biotechnology (DBT), Government of India (NOT availed).
PhD positions open:
Openings for two PhD candidates interested in protein structure-function studies and structure-aided drug design on the ongoing research themes. Candidates with CSIR/DBT/ICMR fellowships can reach me at email@example.com for further discussions.
- Best paper presentation: “The diverse roles of Zn-metallopeptidases in health and diseases”, 3rd International Conference on Recent Trends in Bioengineering (ICRTB 2020), 31 Jan-01 Feb 2020, MITBIO, PUNE, India.
- INDO-US Science and Technology Forum (IUSSTF), TRAVEL AWARD, 2011, to attend MTMS-2011, IIT Powai, India.
- First Rank for PhD course work (April-September 2007), Division of Biochemical sciences, National Chemical Laboratory (NCL), PUNE, India.
- Awarded Junior and senior research fellowships in CSIR/UGC-NET (2006-2011) and ICMR, 2005 (Not availed), Government of India.
- University 1st Rank for Master of Science in Biochemistry, 2005, DAVV, Indore, India.
|Prabakaran A, CSIR-JRF (November 2020- present)|
M.Sc Biotechnology (2018-2020) Madurai Kamaraj University, Madurai.
B.Sc Advanced zoology and biotechnology (2015-2018) Loyola college, Chennai.
|Shalini Ghosh, (M.Sc Intern, February 2021-July 2021)|
M.Sc Applied Microbiology (2019-2021), Vellore Institute of Technology (VIT), Vellore.
B.Sc (Hons) Microbiology (2016-2019), Institute of Genetic Engineering, MAKAUT, Kolkata.
|Nirban Dey (M.Sc Intern, February 2021-July 2021)|
M.Sc Applied Microbiology (2019-2021), Vellore Institute of Technology (VIT), Vellore.
B.Sc (Hons) Microbiology (2019-2021), Institute of Genetic Engineering, MAKAUT, Kolkata.
|Namitha N A, (M.Sc Intern, January 2021-July 2021)|
M.Sc Bioinformatics and Applied Biotechnology (2019-2021) IBAB, Bangalore, Karnataka.
B.Sc Biotechnology (2016-2019) Amrita School of Biotechnology, Amrita University, Kollam, Kerala.