Winner: 2021 Chemistry Biology Interface Division open award: Khorana Prize
Dr G. Marius
National Institutes of Health
For the development of NMR-based methods to characterize protein assembly, aggregation and amyloidosis.
Dr Clore's research focuses on the development and application of nuclear magnetic resonance (NMR) to study the structure and dynamics of biological macromolecules and their complexes in solution. He is particularly interested in exploring fundamental questions associated with protein dynamics and macromolecular interactions. His research group is using NMR to detect and characterise short-lived, sparsely-populated states of macromolecules.
Many important biological processes proceed through transient intermediate states that comprise only a fraction of the overall population of a molecular system. As a result, they are invisible (ie, 'dark') to conventional biophysical techniques (including crystallography, cryo-electron microscopy and single molecule spectroscopies). The group's research provides new insights into macromolecular recognition and assembly, and the effect of the invisible 'dark' state on some NMR observables so that its footprint is readily observed in measurements on the NMR visible species.
Their work on amyloid-β, huntingtin and Hsp40 has implications for the treatment of a range of neurodegenerative diseases associated with protein aggregation and amyloid formation.
Biography
Dr Marius Clore FRS is a Distinguished Investigator in the Laboratory of Chemical Physics at the National Institutes of Health (NIH). He is known for pioneering three-dimensional structure determination of biological macromolecules, and developing NMR methods for characterising the structure and dynamics of rare, short-lived conformational states. After receiving his undergraduate degree in Biochemistry from University College London (UCL) in 1976, Dr Clore gained a medical degree from UCL Medical School (1979), and a doctorate from the MRC National Institute for Medical Research, London (1982). He joined the scientific staff of the MRC National Institute for Medical Research in 1980, becoming head of the biological NMR group at the Max-Planck Institute for Biochemistry (Martinsried, Germany) in 1984. He moved to the NIH in 1988.
He is a member of the United States National Academy of Sciences, and a Fellow of the Royal Society, the Royal Society of Chemistry and the American Academy of Arts and Sciences. His awards include the Royal Society of Chemistry Centenary Prize and the Biochemical Society Centenary Award. Dr Clore's research has revealed new insights into macromolecular recognition, conformational transitions, and assembly processes. Examples include how transcription factors locate their specific DNA binding site within a sea of non-specific DNA; the role of encounter complexes in protein-protein association; the interplay of conformational selection and induced fit in protein-ligand interactions; transient interactions of intrinsically disordered and partially folded polypeptides with large megadalton macromolecular assemblies; and characterisation at atomic resolution of the early stages of amyloid-? protofibril formation, and of pre-nucleation, transient oligomerisation of huntingtin prior to fibril formation.
Chemistry is the foundation of life and all of the life sciences.
Dr G. Marius Clore
Q&A
How did you first become interested in chemistry?
I became very interested in both physics and chemistry at a very early age. I was especially interested in carrying out chemistry experiments at home, something which would not be possible these days (and was not without some mishaps which fortunately did not end badly). I was particularly inspired by Peter Pauling (son of Linus Pauling), then a lecturer in Chemistry at UCL and a good friend of my parents, who allowed me to take everything home from his lab that I could carry!
Who or what has inspired you?
Max Perutz. A truly great scientist. Sir Arnold Burgen who gave me the opportunity to take up NMR spectroscopy.
What motivates you?
Discovering the unknown and solving problems that everybody else previously thought were impossible.
Why is chemistry important?
Chemistry is the foundation of life and all of the life sciences.