Mike Murphy

Mike Murphy

Programme Leader

Targeting therapeutic and probe molecules to mitochondria, mitochondrial radical production and redox signalling

Reactive oxygen species (ROS) produced by mitochondria cause oxidative damage that impairs the ability of mitochondria to make ATP and to carry out their metabolic functions. They may participate also in cellular redox signalling pathways. One important aspect of our work is to investigate how oxidative damage to mitochondria contributes to human pathologies. We have worked out a way of targeting small bioactive molecules, such as antioxidants, to mitochondria in order to counter the effects of ROS and to examine the effects of doing so at cellular and whole animal levels. The bioactive molecule is attached chemically to a lipophilic cation such triphenylphosphonium. These cations accumulate selectively, first in the cytosol, driven by the plasma membrane potential, and then several-hundred fold in the matrix of mitochondria, driven by the membrane potential across the inner membrane. A second important aspect is to determine whether and how mitochondrial ROS alters the activities of proteins in putative signalling and protective pathways by reversibly modifying the redox state of critical protein thiols in mitochondria. We use a range of free radical and proteomic approaches to identify the proteins involved, and to identify the cysteine residues and any redox modifications. Finally, we take this information and use it to rationally design potential therapies for diseases that arise from mitochondria dysfunction. Currently our main focus for therapy is the ischaemia/reperfusion injury that arises from stroke and heart attack.

Publication profile

Research areas

Mitochondrial Exomarkers
Mitochondrial Therapies
Thiol Proteomics

Group Members

Research support

  • Georgina Bates
  • Tracy Prime

Post-docs

  • Dr. Andrew James
  • Dr. Angela Logan
  • Jan Miljkovic
  • Amin Mottahedin
  • Hiran Prag

Post-graduate students

  • Fay Allen
  • Timothy Beach
  • Nils Burger
  • Filip Cvetko
  • Blanca Dominguez Loidi
  • Anja Gruszczyk
  • Nicole Torelli
  • Marcela Usmari Moraes

Visitors

  • Johannes Bargehr
  • Alison Gane
  • Margaret Huang
  • Dee (Duvaraka) Kulaveerasingam
  • Marie-Christine Laurent
  • Min Park
  • Tim Young

Publications

All publications

Biography

Education & Employment

1980-1984
BA in Chemistry, first class honours, first in class, Trinity College, Dublin, Ireland
1984-1987
PhD, Department of Biochemistry, University of Cambridge, UK
1988
Associate Research Scientist, Columbia University College of Physicians and Surgeons, New York
1989
Teacher with Voluntary Services Overseas (London) in Zimbabwe
1990-1992
Lecturer, Biochemistry Department, Trinity College, Dublin, Ireland
1992-2001
Lecturer/Senior Lecturer/Associate Professor, Biochemistry Department, University of Otago, New Zealand
1999
Sabbatical Visitor, Biozentrum, University of Basel, Switzerland
1999
Sabbatical Visitor, University of Alabama at Birmingham, USA
2000-2001
Associate Dean for Research, Otago School of Medical Sciences
2001-present
Programme Leader, MRC Mitochondrial Biology Unit, University of Cambridge, UK

Awards & honours

1982
C Walter Jones Prize in Organic Chemistry
1982-1987
Foundation Scholarship
1984
Cocker Medal for Experimental Chemistry
1984-1987
Open Research Studentship, Peterhouse, University of Cambridge
2000
Applied Biosystems Medal, NZ Society of Biochemistry and Molecular Biology
2000
Research Medal of the New Zealand Association of Scientists
2001-present
Honorary Fellow, Depts of Chemistry and Biochemistry, University of Otago
2008
The Nathan O. Kaplan Lecturer, University of California, San Diego
2012
Honorary Fellow of the Royal Society of New Zealand (Hon FRSNZ)
2016
Keilin Memorial Lecture and Medal
2016-present
Wellcome Trust Investigator
2016-present
Honorary Research Professor, Chemistry Department, University of Otago, NZ
2017
The 2017 Gopal Singhal Lecturer, Chemistry Department, Wayne State University, USA
2018
The 2018 Basic Science Lecturer, Society for Free Radical Research-Europe
2018-present
Personal Professorship, University of Cambridge

Editorial Boards

2016-present
Cell Metabolism: Editorial board
2012-present
Free Radical Biology and Medicine: Editorial board
2013-present
Redox Biology: Editorial board
2013-present
Redox Report: Editorial board
2010-present
Free Radical Research: Editorial board
2017-present
British Heart Foundation: Project grants committee
2017-present
Novintum Biotech, Switzerland: Scientific advisory board
2001-present
Antipodean Pharmaceuticals, New Zealand: Scientific advisory board
2017-present
EU H2020 FET-Open program (Future and Emerging Technologies) - Lumiblast: Expert monitor
Present
Takeda Pharmaceuticals, Japan; Cayman Chemicals, USA; Flagship Ventures, USA: Consultant
2003-2016
Biochemical Journal: Deputy chair (2007-2016), Editorial board (2003-2016)
1999-2014
Archives of Biochemistry and Biophysics: Editorial board
2009-2011
Current Opinion in Investigational New Drugs: Editorial board
2002-2015
FEBS Journal: Editorial advisory panel
2003–2007
Biochemical Society Theme Panel III (Bioenergetics and Metabolism)
2010-2013
Telethon Italy: Scientific committee
2009-2011
Buck Institute for Aging Research, USA: External advisory board for the U54 Interdisciplinary Research Center

Patents

Mitochondrially targeted antioxidants, Michael P. Murphy and Robin A. J. Smith, United States Patent US 6,331,532.

Mitochondrially targeted antioxidants, Michael P. Murphy and Robin A. J. Smith, United States Patent US 6,984,636.

Mitochondrially targeted antioxidants, Michael P. Murphy and Robin A. J. Smith, Australian Patent AU 763179.

Mitochondrially targeted antioxidants, Michael P. Murphy and Robin A. J. Smith, New Zealand Patent NZ 505352.

Mitochondrially targeted antioxidants, Michael P. Murphy and Robin A. J. Smith, United States Patent US 7,109,189.

Mitochondrially targeted antioxidants, Michael P. Murphy and Robin A. J. Smith, New Zealand Patent NZ 538371.

Triphenylphosphonium thionitrite nitric oxide donors, Michael P. Murphy and Robin A. J. Smith European Patent EP2066680.

Triphenylphosphonium thionitrite nitric oxide donors, Michael P. Murphy and Robin A. J. Smith. Canadian Patent CA 2664744.

Triphenylphosphonium thionitrite nitric oxide donors, Michael P. Murphy and Robin A. J. Smith. United States Patent US 12/732,909.

Mitoquinone derivatives used as mitochondrially targeted antioxidants, Michael P. Murphy and Robin A. J Smith, United States patent US 7,888,334.

Mitochondrially targeted antioxidants, Michael P Murphy and Robin A. J Smith, Canadian Patent  CA 2311318

Websites

Lab Alumni with Faculty Positions:

Helena Cocheme - MRC Clinical Sciences Centre, London, UK

Jan Trnka - Charles University, Prague, Czech Republic

Christina Dahm - Aarhus University, Aarhus, Denmark

Aleksandra Filipovska - Harry Perkins Institute of Medical Research, Perth, Australia

Thomas Hurd - University of Toronto, Toronto, Canada

Edward Chouchani - Harvard Medical School and Dana-Farber Cancer Institute, Boston, USA

 

Collaborator Websites

Cambridge Biorepository for Translational Research