Judy Hirst FRS (accordion)
Director
MRC Investigator
Other titles
Mitochondrial complex I: An intricate energy-converting machine, a cornerstone of mitochondrial metabolism, and a locus of mitochondrial dysfunction and disease
Mammalian complex I (NADH:ubiquinone oxidoreductase) is a crucial mitochondrial enzyme. It oxidises NADH from the tricarboxylic acid cycle, fatty-acid oxidation and glycolysis, reduces ubiquinone for the rest of the respiratory chain, and transports protons across the inner mitochondrial membrane to support ATP synthesis. It is also a major contributor to cellular reactive oxygen species production and oxidative stress. With nine redox cofactors and 44 different subunits, encoded on both the nuclear and mitochondrial genomes, mammalian complex I is one of the largest, most complicated enzymes in the cell. We aim to determine the structure of mammalian complex I, and its mechanisms of catalysis and reactive oxygen species production.
Complex I is linked to medicine on many different levels: from mutations in its subunits and assembly factors that cause mitochondrial diseases, through reactive oxygen species production and oxidative damage (relevant to neurodegenerative diseases such as Parkinson's disease), to complex I as a potential drug target in diabetes, ischaemia-reperfusion and cancer, and complex I-linked drug side effects. We aim to build on our knowledge of structure and mechanism to understand human complex I dysfunctions on the molecular level, and to elucidate the role of complex I in genetically, environmentally and pharmacologically-linked mitochondrial dysfunctions.
Education
1994-1997 D. Phil. in chemistry, Lincoln College, Oxford
1990-1994 MA in chemistry, St. John’s College, Oxford
1985-1990 King James’s School and Greenhead College, Huddersfield
Professional Career
| 2020-present | Director, Medical Research Council Mitochondrial Biology Unit, University of Cambridge (Interim Director 2019-2020, Deputy Director 2014-2019, Assistant Director 2011-2014) |
| 1999-present | Programme Leader, Medical Research Council Mitochondrial Biology Unit, Cambridge |
| 1998-1999 | Wellcome Trust Prize International Research Fellowship at The Scripps Research Institute, La Jolla, California |
| 2015-present | Dean of College, Corpus Christi College, Cambridge |
| 2011-present |
Fellow and Director of Studies in chemistry, Corpus Christi College, Cambridge
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Prizes, awards and achievements
| 2020 | Keilin Memorial Lecture and Medal |
| 2019 | Elected Fellow of the Academy of Medical Sciences (FMedSci) |
| 2018 | Elected Fellow of The Royal Society (FRS) |
| 2018 | Royal Society of Chemistry Interdisciplinary Prize: "Awarded for combining structural, biochemical and physical chemical techniques to pioneer studies of energy conversion in complex redox enzymes” |
| 2017 | Chair of the Gordon Research Conference on Bioenergetics: from Molecular Structures and Mechanisms to Cellular Bioenergetics in Health and Disease, New Hampshire, USA |
| 2012 | Elected Fellow of the Royal Society of Chemistry |
| 2012 | Royal Society of Chemistry Norman Heatley Award: “For her work as one of the leading international experts on the chemistry of mitochondrial electron transport enzymes” |
| 2006 | Young Investigator Award (Royal Society of Chemistry Inorganic Biochemistry Discussion Group) "for outstanding contributions to inorganic biochemistry" |
| 2001 | EMBO Young Investigator Award |
| 1995-1997 | Senior Scholarship, Lincoln College, Oxford |
| 1993 | Gibbs Book Prize in Chemistry, Oxford University |
| 1991-1994 | Casberd Scholarship, St. John’s College Oxford |