Judy Hirst FRS

Judy Hirst FRS

Interim Director

Understanding the molecular mechanism of complex I and its roles in human 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.

Publication profile - Google Scholar

Research areas

Group Members

Post-docs

  • Ahmed-Noor Adam Agip
  • Olivier Biner
  • Hannah Bridges
  • Daniel Grba
  • John Wright

Post-graduate students

  • Injae Chung
  • Billy Fisher
  • Owen Jarman
  • Mutum Yaikhomba
  • Zhan Yin

Infrastructure

  • Judy Hirst

Publications

Biography

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

2019 - present
Interim Director, Medical Research Council Mitochondrial Biology Unit, University of Cambridge (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

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