Research & Publications
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 (Accepted)
- 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
Biophysics; Cell Membrane Permeability; Mass Spectrometry; Cell Membrane Structures; Membrane Transport Proteins; Chemicals and Drugs
- Direct determination of oligomeric organization of integral membrane proteins and lipids from intact customizable bilayer. 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 (accepted for publication)