Leicester Institute of Structural and Chemical Biology

Bibek Gooptu

Conformational mechanisms of lung and liver disease

Research summary

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I am a Clinician Scientist interested in understanding the relationship between disease relevant protein behaviours and disease, to identify new drug targets. My research focuses on diseases mediated by inflammation and fibrosis in the lung and liver where there is major unmet clinical need. We study the effects of disease mutations and environmental stimuli upon protein folding and conformational behaviour in serpinopathies (such as a1-antitrypsin deficiency), using X-ray crystallography, NMR spectroscopy, cryo-EM, and native MS. Subsequently, we dissect downstream mechanisms in cells using cell biology and proteomic methods, relate these to disease biology, and undertake proof-of-principle studies into novel therapeutic strategies.

To study interstitial lung diseases my group now also focuses upon what we term the gal-3-fibrosome: a cell-surface interactome that stabilises pro-fibrotic and injury response mediators and can cluster them spatiotemporally. We are undertaking cell biology and interactomic studies to define direct interactions and validate them for pathophysiological significance. These will be further defined in terms of the high resolution structures of sub-complexes within the gal-3-fibrosome and the conformational behaviour of effector domains using structural and biophysical studies.

The cross-cutting nature of my research and clinical interests provides an interface between LISCB and the NIHR Leicester Biomedical Research Centre (BRC)/Leicester Institute of Lung Health where I am a PI, and with clinical practice. I work as a Consultant in Respiratory Medicine at Glenfield Hospital, Leicester and within the London Alpha-1 Antitrypsin Deficiency Service at the Royal Free Hospital in London. In these roles I am also involved in facilitating clinical research in Leicester and London.

Key publications

Group members

Dr Panayiota Stylianou, Dr Chinar Pathak, Charlie Hitchman.

Bench to Business

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Watch Bibek's Bench to Business film.

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