Judy Hirst

Judy Hirst

Deputy 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.

New PDB Files

We apologise for the delay in releasing the PDB files for our recent Nature paper on the structure of mammalian complex I. In the meantime, please click on the link and use the password 'public' to download the submitted versions of these files. These files will be essentially the same as the database release versions.

Research areas

Group Members

Post-docs

  • James Blaza
  • Hannah Bridges
  • Justin Fedor
  • Andrew Jones
  • Febin Varghese

Post-graduate students

  • Ahmed-Noor Adam Agip
  • Polly Marino
  • Riccardo Serreli
  • Zhan Yin

Publications

Biography

Education

1987
King James’s School and Greenhead College, Huddersfield
1994
MA in chemistry, St. John’s College Oxford
1997
D. Phil. in chemistry, Lincoln College Oxford, supervised by Fraser Armstrong

Positions

1998-99
Wellcome Trust Prize International Research Fellowship at The Scripps Research Institute, La Jolla, California with David Goodin
1999 to date
Programme Leader, Medical Research Council, Cambridge (tenured appointment from 2004, Assistant Director in 2011-14, Deputy Director from 2014)
1999 – 2011
Senior Research Fellow, Peterhouse, Cambridge
2011 to date
Fellow of Corpus Christi College, Cambridge and Director of Studies in chemistry

Prizes and awards

1993
Gibbs Book Prize in Chemistry, Oxford University
2001
EMBO Young Investigator Award
2006
Young Investigator Award (Royal Society of Chemistry Inorganic Biochemistry Discussion Group) for outstanding contributions to inorganic biochemistry
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”
2012
Fellow of the Royal Society of Chemistry

Gordon Conference

2015, 2017
Elected chair of the Bioenergetics Gordon Research Conference for 2017, vice chair in 2015