Bibek Gooptu: Research Interests

Current Research Interests

Prof Gooptu’s research defines and therapeutically targets molecular mechanisms of diseases within one or both of the following categories: (i) those driven by protein misfolding/conformational change; (ii) those causing chronic lung disease (COPD and ILD).

A longstanding interest has been in studying the structure and biology of the serpin (serine protease inhibitor) superfamily of proteins, and the diseases that arise from mutations causing their misfolding and/or conformational change (serpinopathies).   The combination of biochemical studies, genotype:phenotype correlation in humans, and X-ray crystallography led to key early insights.  More recently, the Gooptu group has applied NMR, native MS and single particle EM to understand how altered structural dynamics are critical to pathological behaviour in serpins, how serpins self-associate into polymers, and to develop small molecules as therapies. In parallel, proteomic studies have defined in unprecedented detail the subcellular consequences of serpin misfolding and conformational change in cell models of the archetypal serpinopathy, 1-antitrypsin deficiency. An ongoing research collaboration further probes how 1-antitrypsin deficiency results in impaired immunomodulation. These studies are supported by the Wellcome Trust, Alpha-1 Foundation, and MRC and CASE studentships.

Prof Gooptu is now using similar multi-platform approaches to understand how interactions of the chimaeric protein galectin-3 at the surface of eptihelial and fibroblast cells mediate fibrosis in multiple organs. The disease focus is particularly on the devastating lung condition idiopathic pulmonary fibrosis (IPF). This work is currently supported by start-up funding from the University of Leicester and makes use of the state-of-the-art basic and clinical research facilities at the LISCB, the Advanced Imaging Facility and the NIHR Leicester Respiratory Biomedical Research Centre.

 

Recent Research Funding

  • Wellcome Trust Programme Grant (as Co-Investigator, Alpha1-antitrypsin deficiency and the serpinopathies)
  • Alpha-1 Foundation Project Grant (Drug discovery in 1-antitrypsin deficiency)
  • Alpha-1 Foundation Pilot Study Grants (as Co-Investigator, Vitamin D, 1-antitrypsin and airway immunomodulation)
  • NIHR Biomedical Research Centre Award (as consortium member, University of Leicester & Glenfield Hospital, Cardiovascular, Lifestyle and Respiratory)
  • MRC Clinical Research Infrastructure award (within KCL consortium, single cell proteomics and genomics)
  • Wellcome Trust Multi-User Equipment Award (within UCL consortium, 2nd generation ion-mobility, Q-ToF Mass Spectrometer)
  • Wellcome Trust Intermediate Clinical Fellowship (X-ray crystallography, NMR spectroscopy and single particle EM studies of serpinopathies)

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Department of Molecular and Cell Biology

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E: MolCellBiol@le.ac.uk

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