Research

The lipid bilayer surrounding the cells forms a hydrophobic barrier that protects the cellular contents from the environment. However, it also poses problems for the passage/transport of various chemicals and cellular metabolites such as as sugars, amino acids, ions, drugs across the cellular membrane. We are interested in structure-function analysis of various ion channels and transport proteins that facilitate this passage across the cellular membranes and play a central and essential role in a broad spectrum of cellular activities.

Immediate Focus

Immediate focus of our lab is to understand the molecular mechanisms for regulation of Ionotropic Glutamate Receptors (iGluRs) by their Auxiliary Subunits. Ionotropic glutamate receptors mediate excitatory neurotransmission in mammalian nervous system. They are essential for basic nervous system functions, including learning and development, and are involved in a remarkable range of neuronal diseases. Although iGluRs when reconstituted alone in heterologous expression system are capable of eliciting glutamate evoked currents, recent evidence indicates that rather than existing as independent units, native iGluRs are part of a signaling complex that involves transmembrane auxiliary proteins. Several auxiliary proteins have been discovered, which regulate the native iGluR gating properties, pharmacology, and trafficking to synapses. However, there has been essentially no progress towards understanding the structural basis of their regulatory mechanisms. We intend to employ a multipronged approach including X-ray crystallography, electrophysiology, and a variety of biophysical and biochemical techniques to gain insights into how the iGluR auxiliary proteins influence the biophysical properties of their cognate glutamate receptors to modulate synaptic transmission.

Publications

• Kumar J (2022) Ionotropic glutamate delta receptors: The enigma has finally begun to unravel. Neuropharmacology , doi:10.1016/j.neuropharm.2022.108944.

• Vinnakota R, Dhingra S, Kumar J., Ansari MY, Shukla E, Nerkar MD, Kumar J. Role of Neto1 extracellular domain in modulation of kainate receptors. Int J Biol Macromol. 2021 Oct 8;192:525-536. doi: 10.1016/j.ijbiomac.2021.10.001.

• Dutta P, Bharti P, Kumar J. and Maiti, S. Role of actin cytoskeleton in the organization and function of ionotropic glutamate receptors. Curr. Res. Struc. Biol. 2021 https://doi.org/10.1016/j.crstbi.2021.10.001

• Dhingra S, Yadav J and Kumar J. Structure, Function, and Regulation of Kainate receptors. Subcell Biochem. 2021 (In press)

• Burada AP, Vinnakota R, Lambolez B, Tricoire L, Kumar J. Structural biology of ionotropic glutamate delta receptors and their crosstalk with metabotropic glutamate receptors. Neuropharmacology. 2021 Jun 26;108683.

• Bendre AD, Peters PJ, Kumar J. Tuberculosis: Past, present and future of the treatment and drug discovery research. Curr Res Pharmacol Drug Discov. 2021 May 27;100037.

• Bendre AD, Peters PJ, Kumar J. Recent Insights into the Structure and Function of Mycobacterial Membrane Proteins Facilitated by Cryo-EM. J Membr Biol. 2021 May 5; doi.org/10.1007/s00232-021-00179-w.

• Assaiya A, Burada AP, Dhingra S, Kumar J. An overview of the recent advances in cryo-electron microscopy for life sciences. Emerg Top Life Sci. 2021 Mar 24; doi.org/10.1042/ETLS20200295

• George B, Assaiya A, Roy RJ, Kembhavi A, Chauhan R, Paul G, Kumar J*, Ninan SP*. CASSPER is a semantic segmentation-based particle picking algorithm for single-particle cryo-electron microscopy. Commun Biol. 2021 Feb 15;4(1):200. doi:/10.1038/s42003-021-01721-1 (*corresponding authors)

• Burada AP, Vinnakota R, Bharti P, Dutta P, Dubey N, Kumar J. Emerging insights into the structure and function of ionotropic glutamate delta receptors. Br J Pharmacol. 2020 Nov 4; doi: 10.1111/bph.15313

• Burada AP, Vinnakota R, Kumar J. The architecture of GluD2 ionotropic delta glutamate receptor elucidated by cryo-EM. J Struct Biol. 2020 Aug 1;211(2):107546.

• Kumari J, Bendre AD, Bhosale S, Vinnakota R, Burada AP, Tria G, Ravelli R, Peters PJ, Kumar J. Structural dynamics of the GluK3-kainate receptor neurotransmitter binding domains revealed by cryo-EM. Int J Biol Macromol. 2020 Apr 15; 149:1051-8.

• Burada AP, Vinnakota R, Kumar J. Cryo-EM structures of the ionotropic glutamate receptor GluD1 reveal a non-swapped architecture. Nat Struct Mol Biol. 2020 Jan;27(1):84-91.

• Kumari J, Vinnakota R, Kumar J. Structural and Functional Insights into GluK3-kainate Receptor Desensitization and Recovery. Sci Rep. 2019 Jul 16;9(1):10254. doi: 10.1038/s41598-019-46770-z.

• Meyerson JR, Rao P, Kumar J, Chittori S, Banerjee S, Pierson J, et al. Self-assembled monolayers improve protein distribution on holey carbon cryo-EM supports. Sci Rep. 2014 Nov 18; 4:7084.

• Meyerson JR, Kumar J, Chittori S, Rao P, Pierson J, Bartesaghi A, et al. Structural mechanism of glutamate receptor activation and desensitization. Nature. 2014 Oct 16;514(7522):328-34.

• Zhao H, Berger AJ, Brown PH, Kumar J, Balbo A, May CA, et al. Analysis of high-affinity assembly for AMPA receptor amino-terminal domains. J Gen Physiol. 2013 Jun;141(6):747-9.

• Kumar J, Mayer ML. Functional insights from glutamate receptor ion channel structures. Annu Rev Physiol. 2013; 75:313-37.

• Veran J, Kumar J, Pinheiro PS, Athan A, Mayer ML, Perrais D, et al. Zinc potentiates GluK3 glutamate receptor function by stabilizing the ligand binding domain dimer interface. Neuron. 2012 Nov 8;76(3):565-78.

• Zhao H, Berger AJ, Brown PH, Kumar J, Balbo A, May CA, et al. Analysis of high-affinity assembly for AMPA receptor amino-terminal domains. J Gen Physiol. 2012 May;139(5):371-88.

• Kumar J, Schuck P, Mayer ML. Structure and assembly mechanism for heteromeric kainate receptors. Neuron. 2011 Jul 28;71(2):319-31.

• Pandey SP, Minesinger BK, Kumar J, Walker GC. A highly conserved protein of unknown function in Sinorhizobium meliloti affects sRNA regulation similar to Hfq. Nucleic Acids Res. 2011 Jun;39(11):4691-708.

• Kumar J, Mayer ML. Crystal structures of the glutamate receptor ion channel GluK3 and GluK5 amino-terminal domains. J Mol Biol. 2010 Dec 10;404(4):680-96.

• Das U, Kumar J, Mayer ML, Plested AJR. Domain organization and function in GluK2 subtype kainate receptors. Proc Natl Acad Sci U S A. 2010 May 4;107(18):8463-8.

• Kumar J, Schuck P, Jin R, Mayer ML. The N-terminal domain of GluR6-subtype glutamate receptor ion channels. Nat Struct Mol Biol. 2009 Jun;16(6):631-8.

Book chapters:

• Assaiya A, Bhar S and Kumar J (2021). Advances in Sample Preparation and Data Processing for Single-particle Cryo-Electron Microscopy. In: Tripathi T. (eds) Advances in Protein Molecular and Structural Biology Methods. Methods in Molecular and Structural Biology, Academic Press Elsevier, USA (In Press). [ISBN: 978-032-39-0264-9].

• Kumari J, Dhingra S, Kumar J Fluorescence-Based Screening of Membrane Proteins for Structural Studies. In: Shukla AK, editor. Chemical and Synthetic Approaches in Membrane Biology. New York, NY: Springer; 2017,141-55. Springer Protocols Handbooks.

Commentary:

• Chaudhry C, Scimemi A, Kumar J Building and breaking interfaces: how a receptor takes shape. J Neurosci. 2011 Jul 27;31(30):10749-51.

• Burada A P, Rajesh Vinnakota, Kumar J (2021) Elucidating the Architecture of Orphan Glutamate Delta Receptor-1 by Cryo-EM. ESRF Highlights. 34, 55-57

Preprints:

• Paul D, Jani K, Kumar J, Chauhan R, Seshadri V, Lal G, et al. Phylogenomic analysis of SARS-CoV-2 genomes from western India reveals unique linked mutations. bioRxiv. 2020 Aug 4;2020.07.30.228460.

• Maitra A, Raghav S, Dalal A, Ali F, Paynter VM, Paul D, et al. PAN-INDIA 1000 SARS-CoV-2 RNA Genome Sequencing Reveals Important Insights into the Outbreak. bioRxiv. 2020 Aug 3;2020.08.03.233718. *Part of consortium

For complete list of publications, click HERE

Awards/Fellowships/Grants

Awarded DBT-Wellcome Trust India Alliance Senior Fellowship (December 2021)

Awarded EMBO-STF (Jull 2017)

Awarded Ramanujan Fellowship (January 2014), Department of Science and Technology, Government of India, New Delhi

Awarded Wellcome Trust/DBT India Alliance Intermediate career fellowship (October 2013), From Wellcome Trust, UK and Department of Biotechnology, Government of India, New Delhi

Fellows Award for Research Excellence (2012), National Institutes of Health, Bethesda, MD, USA

Fellows Award for Research Excellence (2011), National Institutes of Health, Bethesda, MD, USA.

Membership of Journal editorial boards/Advisory committees

1) Communications Biology (Nature) - Editorial Board

2) BMC Molecular and Cell Biology - Associate Editor

3) Plos One- Editorial Board

4) Scientific reports - Editorial Board

5) FEBS OpenBio - Advisory Editorial Board

6) Neuropharmacology - Guest Editor

7) Member of the Technical Monitoring and Advisory Committee for periodic monitoring of the progress of the "GenomeIndia" and "Human Microbiome" initiatives

8) Reviewer for Nature, Nature Structural and Molecular Biology, Communications Biology, ActaD, Journal of Molecular Biology, Journal of Biological Chemistry, Journal of Structural Biology, Journal of Lipid Research, Scientific Reports, Plos One, etc.

Funding

Our laboratory is funded by Department of Biotechnology and Science and Engineering Research Board, New Delhi. The lab was earlier supported by DBT/Wellcome Trust India Alliance Intermediate Fellowship.

Opportunities

Highly motivated scientists interested in membrane protein structure and function with strong background in protein biochemistry and molecular biology methods are always encouraged to apply for post-doc positions.

Students interested in MS/M.Sc project training projects (3-12 months), please email janesh@nccs.res.in or academics@nccs.res.in