Steven J. Gamblin
Structural biologist and Fellow of the Royal Society who solved the crystal structure of active mammalian AMPK, the cell's energy sensor and the main counterweight to mTORC1, and who now directs the scientific platforms of the Francis Crick Institute
Director of Scientific Platforms, The Francis Crick Institute · Director of Science Operations, Crick (from 2015) · Director of Research (2011) and Joint Head of the Division of Molecular Structure (2005), MRC National Institute for Medical Research, Mill Hill · group leader, NIMR Division of Protein Structure (from 1994) · postdoc, Stephen Harrison lab, Harvard University · PhD in enzymology and crystallography with Herman Watson, University of Bristol
Scientific Platforms, The Francis Crick Institute (London, England, United Kingdom) ↗
AMPK is the cell's fuel gauge. When energy runs low, the cell has more AMP and ADP (the spent forms of the energy carrier ATP), AMPK switches on, and one of the first things it does is put the brakes on mTORC1 so that the cell stops spending energy on growth. The 2011 Nature paper XIA2011, with Steven Gamblin as senior author, from his group at the MRC National Institute for Medical Research in London, showed how AMPK reads these signals. AMP binding to AMPK's regulatory gamma part protected the enzyme from losing the phosphate group that keeps it switched on. ADP binding to one site gave the same protection, though it did not directly activate the enzyme the way AMP does. The team also solved the crystal structure of an active AMPK complex, giving a 3D picture of how the energy-sensing part talks to the enzyme part.
The finding changed the textbook picture: ADP, which is far more plentiful than AMP in a stressed cell, can also keep AMPK on. That makes the energy brake on mTORC1 more sensitive than had been thought. The work was done with purified proteins and cells.
Gamblin studied biochemistry at the University of Bristol and did a PhD there with Herman Watson on enzymes and protein crystallography, followed by postdoctoral work in Stephen Harrison's lab at Harvard. In 1994 he set up his own lab in the new Division of Protein Structure at the National Institute for Medical Research, using structural biology to study proteins involved in disease. He became Joint Head of the Division of Molecular Structure in 2005 and the institute's Director of Research in 2011, the year he was elected a Fellow of the Royal Society. When NIMR became part of the Francis Crick Institute he became its Director of Science Operations in 2015, and he is now Director of Scientific Platforms, overseeing the shared technology facilities. He is also a Fellow of the Academy of Medical Sciences and a member of EMBO.
Milestones in the Atlas
A selection, not a full bibliography: only papers that meet the Atlas inclusion criteria.
| Year | Evidence | Study |
|---|---|---|
| 2011 | M | Structure of mammalian AMPK and its regulation by ADP XIA2011 Senior author: showed that AMP and ADP protect AMPK from dephosphorylation and solved the crystal structure of an active AMPK complex. |
Co-authors in the Atlas 1
People with a profile here who share at least one study with Steven J. Gamblin.
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- David Carling Biochemist who heads the Cellular Stress group at the MRC Laboratory of Medical Sciences in London and has spent decades working out how the energy sensor AMPK is switched on and what it controls
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