Kallol Gupta, PhD
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Research Summary
Nanoscale spatiotemporal organization of proteins and lipids in the cell membranes is fundamental to all living cells. Impairments of such organizations are deleterious towards cellular health and causal towards a range of disease conditions, such as various forms of cancers and neurodegenerative disorders. Addressing this, we develop quantitative tools that provide simultaneous molecular and nanometer-scale spatial resolution to capture and identify these macromolecular protein-lipid complexes directly from the lipid membrane. Our experimental toolkit consists of native mass spectrometry, quantitative lipidomics, proteomics, single-molecule fluorescence imaging, electron microscopy, and synthetic chemistry. We then apply them to specific membrane-associated signaling pathways that are critical to human health and disease to glean molecular mechanistic insights. We are specifically interested in membrane-associated kinase and GTPase signalings which are leading causes of various forms of cancer and neurodegenerative disorders. The broad questions we are interested in are:
- How do cells regulate and synchronize dynamic organization between proteins and lipids in the organellar membranes to generate signaling response to a diverse set of physicochemical stimuli – how do specific disease states perturbs these functional molecular organization leading to perturbed cellular signaling?
- What is the lipid nanodomain around a target membrane protein and how does that regulate the assembly and functions of the molecular complexes formed by the target protein?
- How can we make next-generation quantitative tools that can capture and detect these molecular symphonies between protein and lipid organization in the cell membrane?
We work closely with researchers with varied expertise. While we love the physicists and the chemists who develop novel experimental tools, we cannot live without the biologists and the medics who use these cutting-edge techniques to solve the problems most pertinent to humankind. We even have an anthropologist. We are always interested in innovators, creative thinkers, dreamers, and doers.
If you want to discover the world of native mass spectrometry, we want to hear from you.
If you have ideas, we want to hear from you.
If you are merely curious, we want to hear from you.
We currently have multiple openings for postdocs, graduate students, and research assistants. Contact me directly with your CV and research interests. Click the lab website link for more details
For further details visit: https://www.theguptalab.com/
Selected relevant publications:
- Panda A, Giska F, Duncan A, Welch A, Brown C, McAllister R, Parameswaran H, Goder J, Coleman J, Ramakrishnan S, Pincet F, Guan L, Krishnakumar S, Rothman JE, Gupta K. Direct determination of oligomeric organization of integral membrane proteins and lipids from intact customizable bilayer. Nature Methods 2023 Jun;20(6):891-897. PMID: 37106230
- Giska F, Mariappa, M, Bhattacharyya M, Gupta K. (2022). Deciphering the molecular organization of GET pathway chaperones through native mass spectrometry. Biophysical Journal, 121(7), 1289–1298. doi:10.1016/j.bpj.2022.02.026
- Gaudet RG, Zhu S, Halder A, Kim BH, Bradfield CJ, Huang S, Xu D, Mamiñska A, Nguyen TN, Lazarou M, Karatekin E, Gupta K, MacMicking JD. A human apolipoprotein L with detergent-like activity kills intracellular pathogens. Science. 2021 Jul 16;373(6552):eabf8113. doi: 10.1126/science.abf8113.PMID: 34437126
- Gupta K, Li J, Liko I, Gault J, Bechara C, Wu D, Hopper JTS, Giles K, Benesch JLP, Robinson CV. Identifying key membrane protein lipid interactions using mass spectrometry. Nature Protocol, 2018:13:1106
- Gupta K, Donlan JAC, Hopper JTS, Uzdavinys P, Landreh M, Struwe WB, Drew D, Baldwin AJ, Phillip J. Stansfeld PJ, Robinson CV. The role of interfacial lipids in stabilizing membrane protein oligomers. Nature 2017:541: 421
Coauthors
Research Interests
Biophysics; Cell Membrane Permeability; Mass Spectrometry; Cell Membrane Structures; Membrane Transport Proteins; Chemicals and Drugs
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Selected Publications
- Author Correction: Structure of Geobacter cytochrome OmcZ identifies mechanism of nanowire assembly and conductivityGu Y, Guberman-Pfeffer M, Srikanth V, Shen C, Giska F, Gupta K, Londer Y, Samatey F, Batista V, Malvankar N. Author Correction: Structure of Geobacter cytochrome OmcZ identifies mechanism of nanowire assembly and conductivity. Nature Microbiology 2024, 1-1. PMID: 38684912, DOI: 10.1038/s41564-024-01702-0.
- A proteome-wide quantitative platform for nanoscale spatially resolved extraction of membrane proteins into native nanodiscs.Brown C, Ghosh S, McAllister R, Kumar M, Walker G, Sun E, Aman T, Panda A, Kumar S, Li W, Coleman J, Liu Y, Rothman JE, Bhattacharyya M, Gupta K. A proteome-wide quantitative platform for nanoscale spatially resolved extraction of membrane proteins into native nanodiscs. BioRxiv 2024 PMID: 38405833, DOI: 10.1101/2024.02.10.579775.
- Abstract 1130 Capturing membrane snapshots: A quantitative proteome-wide guide for high-throughput spatially-resolved extraction of membrane proteins for structural/functional studies on native membranesBrown C, Ghosh S, McAllister R, Coleman J, Sun E, Zheng H, Kumar S, Bhattacharyya M, Gupta K. Abstract 1130 Capturing membrane snapshots: A quantitative proteome-wide guide for high-throughput spatially-resolved extraction of membrane proteins for structural/functional studies on native membranes. Journal Of Biological Chemistry 2024, 300: 106334. DOI: 10.1016/j.jbc.2024.106334.
- Imaging nanoscale-spatial oligomeric organization of membrane proteins directly from native membranes at single-molecule resolutionWalker G, Brown C, Ge X, Kumar S, Muzumdar M, Gupta K, Bhattacharyya M. Imaging nanoscale-spatial oligomeric organization of membrane proteins directly from native membranes at single-molecule resolution. Biophysical Journal 2024, 123: 348a. DOI: 10.1016/j.bpj.2023.11.2115.
- Oligomeric organization of membrane proteins from native membranes at nanoscale spatial and single-molecule resolutionWalker G, Brown C, Ge X, Kumar S, Muzumdar M, Gupta K, Bhattacharyya M. Oligomeric organization of membrane proteins from native membranes at nanoscale spatial and single-molecule resolution. Nature Nanotechnology 2023, 19: 85-94. PMID: 38012273, PMCID: PMC10981947, DOI: 10.1038/s41565-023-01547-4.
- Roles for diacylglycerol in synaptic vesicle priming and release revealed by complete reconstitution of core protein machinerySundaram R, Chatterjee A, Bera M, Grushin K, Panda A, Li F, Coleman J, Lee S, Ramakrishnan S, Ernst A, Gupta K, Rothman J, Krishnakumar S. Roles for diacylglycerol in synaptic vesicle priming and release revealed by complete reconstitution of core protein machinery. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2309516120. PMID: 37590407, PMCID: PMC10450444, DOI: 10.1073/pnas.2309516120.
- Studying Membrane Protein–Lipid Specificity through Direct Native Mass Spectrometric Analysis from Tunable ProteoliposomesPanda A, Brown C, Gupta K. Studying Membrane Protein–Lipid Specificity through Direct Native Mass Spectrometric Analysis from Tunable Proteoliposomes. Journal Of The American Society For Mass Spectrometry 2023, 34: 1917-1927. PMID: 37432128, PMCID: PMC10932607, DOI: 10.1021/jasms.3c00110.
- ATG9 vesicles comprise the seed membrane of mammalian autophagosomesOlivas T, Wu Y, Yu S, Luan L, Choi P, Guinn E, Nag S, De Camilli P, Gupta K, Melia T. ATG9 vesicles comprise the seed membrane of mammalian autophagosomes. Journal Of Cell Biology 2023, 222: e202208088. PMID: 37115958, PMCID: PMC10148236, DOI: 10.1083/jcb.202208088.
- Direct determination of oligomeric organization of integral membrane proteins and lipids from intact customizable bilayerPanda A, Giska F, Duncan A, Welch A, Brown C, McAllister R, Hariharan P, Goder J, Coleman J, Ramakrishnan S, Pincet F, Guan L, Krishnakumar S, Rothman J, Gupta K. Direct determination of oligomeric organization of integral membrane proteins and lipids from intact customizable bilayer. Nature Methods 2023, 20: 891-897. PMID: 37106230, PMCID: PMC10932606, DOI: 10.1038/s41592-023-01864-5.
- Structure of Geobacter cytochrome OmcZ identifies mechanism of nanowire assembly and conductivityGu Y, Guberman-Pfeffer M, Srikanth V, Shen C, Giska F, Gupta K, Londer Y, Samatey F, Batista V, Malvankar N. Structure of Geobacter cytochrome OmcZ identifies mechanism of nanowire assembly and conductivity. Nature Microbiology 2023, 8: 284-298. PMID: 36732469, PMCID: PMC9999484, DOI: 10.1038/s41564-022-01315-5.
- Mitoguardin-2–mediated lipid transfer preserves mitochondrial morphology and lipid droplet formationHong Z, Adlakha J, Wan N, Guinn E, Giska F, Gupta K, Melia TJ, Reinisch KM. Mitoguardin-2–mediated lipid transfer preserves mitochondrial morphology and lipid droplet formation. Journal Of Cell Biology 2022, 221: e202207022. PMID: 36282247, PMCID: PMC9597353, DOI: 10.1083/jcb.202207022.
- Deciphering the molecular organization of GET pathway chaperones through native mass spectrometryGiska F, Mariappan M, Bhattacharyya M, Gupta K. Deciphering the molecular organization of GET pathway chaperones through native mass spectrometry. Biophysical Journal 2022, 121: 1289-1298. PMID: 35189106, PMCID: PMC9034188, DOI: 10.1016/j.bpj.2022.02.026.
- Deciphering the molecular organization of Get pathway chaperones through native top-down dissociation of multi-protein complexesGiska F, Mariappan M, Bhattacharyya M, Gupta K. Deciphering the molecular organization of Get pathway chaperones through native top-down dissociation of multi-protein complexes. Biophysical Journal 2022, 121: 333a. DOI: 10.1016/j.bpj.2021.11.1119.
- Chemoselective restoration of para-azido-phenylalanine at multiple sites in proteinsArranz-Gibert P, Vanderschuren K, Haimovich A, Halder A, Gupta K, Rinehart J, Isaacs FJ. Chemoselective restoration of para-azido-phenylalanine at multiple sites in proteins. Cell Chemical Biology 2021, 29: 1046-1052.e4. PMID: 34965380, PMCID: PMC10173106, DOI: 10.1016/j.chembiol.2021.12.002.
- A human apolipoprotein L with detergent-like activity kills intracellular pathogensGaudet RG, Zhu S, Halder A, Kim BH, Bradfield CJ, Huang S, Xu D, Mamiñska A, Nguyen TN, Lazarou M, Karatekin E, Gupta K, MacMicking JD. A human apolipoprotein L with detergent-like activity kills intracellular pathogens. Science 2021, 373 PMID: 34437126, PMCID: PMC8422858, DOI: 10.1126/science.abf8113.
- Identifying key membrane protein lipid interactions using mass spectrometryGupta K, Li J, Liko I, Gault J, Bechara C, Wu D, Hopper JTS, Giles K, Benesch JLP, Robinson CV. Identifying key membrane protein lipid interactions using mass spectrometry. Nature Protocols 2018, 13: 1106-1120. PMID: 29700483, PMCID: PMC6049616, DOI: 10.1038/nprot.2018.014.
- Innenrücktitelbild: Native Desorption Electrospray Ionization Liberates Soluble and Membrane Protein Complexes from Surfaces (Angew. Chem. 46/2017)Ambrose S, Housden N, Gupta K, Fan J, White P, Yen H, Marcoux J, Kleanthous C, Hopper J, Robinson C. Innenrücktitelbild: Native Desorption Electrospray Ionization Liberates Soluble and Membrane Protein Complexes from Surfaces (Angew. Chem. 46/2017). Angewandte Chemie 2017, 129: 14965-14965. DOI: 10.1002/ange.201710562.
- Inside Back Cover: Native Desorption Electrospray Ionization Liberates Soluble and Membrane Protein Complexes from Surfaces (Angew. Chem. Int. Ed. 46/2017)Ambrose S, Housden N, Gupta K, Fan J, White P, Yen H, Marcoux J, Kleanthous C, Hopper J, Robinson C. Inside Back Cover: Native Desorption Electrospray Ionization Liberates Soluble and Membrane Protein Complexes from Surfaces (Angew. Chem. Int. Ed. 46/2017). Angewandte Chemie International Edition 2017, 56: 14771-14771. DOI: 10.1002/anie.201710562.
- The role of interfacial lipids in stabilizing membrane protein oligomersGupta K, Donlan JAC, Hopper JTS, Uzdavinys P, Landreh M, Struwe WB, Drew D, Baldwin AJ, Stansfeld PJ, Robinson CV. The role of interfacial lipids in stabilizing membrane protein oligomers. Nature 2017, 541: 421-424. PMID: 28077870, PMCID: PMC5501331, DOI: 10.1038/nature20820.
- Integrating mass spectrometry with MD simulations reveals the role of lipids in Na+/H+ antiportersLandreh M, Marklund EG, Uzdavinys P, Degiacomi MT, Coincon M, Gault J, Gupta K, Liko I, Benesch JL, Drew D, Robinson CV. Integrating mass spectrometry with MD simulations reveals the role of lipids in Na+/H+ antiporters. Nature Communications 2017, 8: 13993. PMID: 28071645, PMCID: PMC5234078, DOI: 10.1038/ncomms13993.
- Unexpected functional implication of a stable succinimide in the structural stability of Methanocaldococcus jannaschii glutaminaseKumar S, Prakash S, Gupta K, Dongre A, Balaram P, Balaram H. Unexpected functional implication of a stable succinimide in the structural stability of Methanocaldococcus jannaschii glutaminase. Nature Communications 2016, 7: 12798. PMID: 27677693, PMCID: PMC5052720, DOI: 10.1038/ncomms12798.
- Mass spectrometric analysis of dimer-disrupting mutations in Plasmodium triosephosphate isomeraseBandyopadhyay D, Prakash S, Gupta K, Balaram P. Mass spectrometric analysis of dimer-disrupting mutations in Plasmodium triosephosphate isomerase. Analytical Biochemistry 2016, 500: 45-50. PMID: 26919806, DOI: 10.1016/j.ab.2016.02.011.
- High-resolution mass spectrometry of small molecules bound to membrane proteinsGault J, Donlan JA, Liko I, Hopper JT, Gupta K, Housden NG, Struwe WB, Marty MT, Mize T, Bechara C, Zhu Y, Wu B, Kleanthous C, Belov M, Damoc E, Makarov A, Robinson CV. High-resolution mass spectrometry of small molecules bound to membrane proteins. Nature Methods 2016, 13: 333-336. PMID: 26901650, PMCID: PMC4856209, DOI: 10.1038/nmeth.3771.
- Mammalian Neuronal Sodium Channel Blocker μ‑Conotoxin BuIIIB Has a Structured N‑Terminus That Influences PotencyKuang Z, Zhang MM, Gupta K, Gajewiak J, Gulyas J, Balaram P, Rivier JE, Olivera BM, Yoshikami D, Bulaj G, Norton RS. Mammalian Neuronal Sodium Channel Blocker μ‑Conotoxin BuIIIB Has a Structured N‑Terminus That Influences Potency. ACS Chemical Biology 2013, 8: 1344-1351. PMID: 23557677, PMCID: PMC4201638, DOI: 10.1021/cb300674x.
- Cyclic AMP-dependent Protein Lysine Acylation in Mycobacteria Regulates Fatty Acid and Propionate Metabolism*Nambi S, Gupta K, Bhattacharyya M, Ramakrishnan P, Ravikumar V, Siddiqui N, Thomas AT, Visweswariah SS. Cyclic AMP-dependent Protein Lysine Acylation in Mycobacteria Regulates Fatty Acid and Propionate Metabolism*. Journal Of Biological Chemistry 2013, 288: 14114-14124. PMID: 23553634, PMCID: PMC3656268, DOI: 10.1074/jbc.m113.463992.
- Rapid mass spectrometric determination of disulfide connectivity in peptides and proteinsBhattacharyya M, Gupta K, Gowd KH, Balaram P. Rapid mass spectrometric determination of disulfide connectivity in peptides and proteins. Molecular Omics 2013, 9: 1340-1350. PMID: 23467691, DOI: 10.1039/c3mb25534d.
- Distinct Disulfide Isomers of μ‑Conotoxins KIIIA and KIIIB Block Voltage-Gated Sodium ChannelsKhoo KK, Gupta K, Green BR, Zhang MM, Watkins M, Olivera BM, Balaram P, Yoshikami D, Bulaj G, Norton RS. Distinct Disulfide Isomers of μ‑Conotoxins KIIIA and KIIIB Block Voltage-Gated Sodium Channels. Biochemistry 2012, 51: 9826-9835. PMID: 23167564, PMCID: PMC4131687, DOI: 10.1021/bi301256s.
- A Bioorthogonal Chemoenzymatic Strategy for Defined Protein Dendrimer AssemblyGupta K, Singh S, Gupta K, Khan N, Sehgal D, Haridas V, Roy RP. A Bioorthogonal Chemoenzymatic Strategy for Defined Protein Dendrimer Assembly. ChemBioChem 2012, 13: 2489-2494. PMID: 23042694, DOI: 10.1002/cbic.201200559.
- Lipopeptides from the Banyan Endophyte, Bacillus subtilis K1: Mass Spectrometric Characterization of a Library of FengycinsPathak KV, Keharia H, Gupta K, Thakur SS, Balaram P. Lipopeptides from the Banyan Endophyte, Bacillus subtilis K1: Mass Spectrometric Characterization of a Library of Fengycins. Journal Of The American Society For Mass Spectrometry 2012, 23: 1716-1728. PMID: 22847390, DOI: 10.1007/s13361-012-0437-4.
- Combined Electron Transfer Dissociation–Collision-Induced Dissociation Fragmentation in the Mass Spectrometric Distinction of Leucine, Isoleucine, and Hydroxyproline Residues in Peptide Natural ProductsGupta K, Kumar M, Chandrashekara K, Krishnan KS, Balaram P. Combined Electron Transfer Dissociation–Collision-Induced Dissociation Fragmentation in the Mass Spectrometric Distinction of Leucine, Isoleucine, and Hydroxyproline Residues in Peptide Natural Products. Journal Of Proteome Research 2011, 11: 515-522. PMID: 22111579, DOI: 10.1021/pr200091v.
- Mass spectrometric identification of an intramolecular disulfide bond in thermally inactivated triosephosphate isomerase from a thermophilic organism Methanocaldococcus jannaschiiBanerjee M, Gupta K, Balaram H, Balaram P. Mass spectrometric identification of an intramolecular disulfide bond in thermally inactivated triosephosphate isomerase from a thermophilic organism Methanocaldococcus jannaschii. Rapid Communications In Mass Spectrometry 2011, 25: 1915-1923. PMID: 21698673, DOI: 10.1002/rcm.5058.
- Ammonia Channeling in Plasmodium falciparum GMP Synthetase: Investigation by NMR Spectroscopy and Biochemical AssaysBhat JY, Venkatachala R, Singh K, Gupta K, Sarma SP, Balaram H. Ammonia Channeling in Plasmodium falciparum GMP Synthetase: Investigation by NMR Spectroscopy and Biochemical Assays. Biochemistry 2011, 50: 3346-3356. PMID: 21413787, DOI: 10.1021/bi1017057.
- Disulfide Bond Assignments by Mass Spectrometry of Native Natural Peptides: Cysteine Pairing in Disulfide Bonded ConotoxinsGupta K, Kumar M, Balaram P. Disulfide Bond Assignments by Mass Spectrometry of Native Natural Peptides: Cysteine Pairing in Disulfide Bonded Conotoxins. Analytical Chemistry 2010, 82: 8313-8319. PMID: 20843009, DOI: 10.1021/ac101867e.
- Identification of α- and β-hydroxy acid containing cyclodepsipeptides in natural peptide mixtures using negative ion mass spectrometryThakur SS, Ranganayaki RS, Gupta K, Balaram P. Identification of α- and β-hydroxy acid containing cyclodepsipeptides in natural peptide mixtures using negative ion mass spectrometry. Journal Of The American Society For Mass Spectrometry 2009, 20: 2221-2228. PMID: 19811932, DOI: 10.1016/j.jasms.2009.08.010.