Peter Malcolm Colman

By May 16th, 2014

Peter Colman AC FRS FAA FTSE was one of the key scientists involved in determining the structure of influenza virus neuraminidase. This medical breakthrough led to the development of Relenza®, a drug that is effective against all known strains of the influenza virus.

Biography

Peter Malcolm Colman was born in Adelaide in 1944. On completion of his secondary schooling at Unley High School he studied Physics at Adelaide University, being awarded the Philips prize for Honours Physics in 1965, and completing his PhD in 1969.

From 1969 to 1972, he was a Post Doctoral Fellow at the University of Oregon with Professor Brian Matthews , where, together with Hans Jansonius, they determined the structure of the heat stable enzyme thermolysin. From 1972 to 1975 he was a Post Doctoral Fellow at the Max Planck Institute, Munich with Professor Robert Huber who subsequently was awarded the Nobel Prize for Chemistry in 1988. In Munich Colman determined the first structure of an intact antibody molecule and, together with Hans Deisenhofer, also later a Nobel Laureate, the antibody Fc fragment.

In 1975, Peter Colman was awarded a Queen Elizabeth II Fellowship to conduct research in the laboratory of Professor Hans Freeman at the University of Sydney. There he continued work on antibody fragments whilst collaborating with Mitchell Guss, John Ramshaw and others on the structure of the blue copper-containing redox protein plastocyanin. Shortly before leaving Sydney, work began on crystals of influenza virus neuraminidase (produced by Dr Graeme Laver at the Australian National University’s John Curtin School of Medical Research).

In 1978, he joined CSIRO’s Division of Protein Chemistry in Parkville to form a crystallography group with emphasis on the structure of globular proteins. The neuraminidase problem became his major interest when he moved to the Parkville laboratory where there already was a major influenza virus program being run by Colin Ward.

In 1989, Dr Colman was appointed Foundation Chief of the CSIRO Division of Biomolecular Engineering, and in 1990 Foundation Director of the Biomedical Research Institute, which was co-located with the Division in Parkville. He remained Chief of Division of Biomolecular Engineering until 1997 when he resigned to concentrate on the Biomolecular Research Institute.

He was a Founding Member of the Board of Directors of Biota Holdongs Ltd from 1985 to 1991 and was a Founding Member of the Board of Directors of Starpharma Ltd serving on the Starpharma Board for more than ten years as both a Director and a member of its Research Committee. He resigned from the Starpharma Board in 2008.

In 2001, Dr Colman moved to the Walter and Eliza Hall Institute of Medical Research in Parkville to establish and lead the Structural Biology Division. There his research interest has been on the structural biology of proteins in the BCL-2 family and methods for antagonising their function.

Research contributions at CSIRO

The research on the determination of the 3D structure of the influenza virus neuraminidase begun in 1978 culminated in the development of Relenza® by CSIRO and the Victorian College of Pharmacy funded by the Australian biotechnology company Biota Holdings Limited. The influenza work involved the following:

  • the determination of the 3D structures of two N2 neuraminidase molecules of human influenza Type A viruses isolated ten years apart (1957 and 1967) employing novel mathematical techniques of combining the data of two crystal systems with different strains of the virus. The work carried out with Jose Varghese was published in back-to-back articles in the 11 May 1983 issue of the prestigious journal Nature with a hand drawing by Varghese of the neuraminidase molecule on the front cover. Interpretation of the structure at that time was greatly aided by the amino acid sequence of the neuraminidase emerging from the work of Colin Ward and colleagues.
  • the determination of the structure of sialic acid complexed with influenza virus N2 neuraminidase that was used in the design of the anti-influenza virus drug Relenza
  • the determination of the structures of complexes of N2 neuraminidase and potential neuraminidase inhibitors leading to the design and development of zanamavir, now marketed as Relenza®
  • the subsequent development of Tamiflu® by the US-based company Gilead Sciences and Roche was also based on this CSIRO research
  • the determination of the structural basis for drug resistance in influenza virus neuraminidase and the prediction of the emergence of drug resistance strains, particularly to Tamiflu®, which recently has been verified.

In a related activity, Peter Colman and CSIRO colleagues Jose Varghese and Peter Tulloch and their international collaborators published in Nature in 1987 the first structure of a viral antigen / antibody complex and again made the cover. In this landmark paper they proposed the ‘hand-shake’ model of antibody-antigen interaction.

Other protein crystallography projects included the determination of the structure of phaseolin, the first of several seed storage proteins that were solved (with Mike Lawrence, Jose Varghese, Eikichi Suzuki and Peter Tulloch) and the development of a metric Sc to quantify the geometric fit of two protein surfaces (with Mike Lawrence). This measure of shape complementarity of protein-protein interfaces has since proved enormously successful. The paper has been cited over 410 times and has been used by others to assist for example: understanding the interaction between the T-cell receptor and the MHC/antigen complex [Garcia et al., 1998, Science, 279: 1166-1172] and understanding the intimate packing within amyloid fibres [Nelson et al., 2005, Nature, 435: 773-778].

By 2008, Peter Colman was a named inventor on five patents and had published a total of 134 publications including: 21 review articles, 21 conference proceedings and 92 original papers.

Honours and awards

Fellowships and prizes

For his role in the discoveries leading to the development of Relenza®, Dr Colman received a number of awards and honours, including:

Fellowships

2014 Fellow of the Royal Society
1997 Fellow of the Australian Academy of Technological Sciences and Engineering
1988 Fellow of the Australian Academy of Science

Awards

2017 Companion of the Order of Australia (AC)
2008 Victoria Prize
2004 Mayne Florey Medal
2001 Centenary Medal
2000 Doctor of Science (honoris causa), University of Sydney
1999 James Cook Medal (Royal Society of NSW)
1997 Fellow of the Australian Academy of Technological Sciences and Engineering
1996 Australia Prize for excellence in pharmaceutical design – along with Dr Graeme Laver (ANU) and Professor Mark von Itzstein (Victoria College of Pharmacy, Monash University). The prize was shared with Professor Paul Janssen, founder of Janssen Pharmaceutica, N.V.
1995 Australian Academy of Science Burnet Medallist and Lecturer
1988 Australian Society for Biochemistry and Molecular Biology Lemberg Lecturer and Medallist
1988 Fellow of the Australian Academy of Science
1987 International Lorne Protein Conference Leach Lecturer and Medallist
1986 Royal Society of Victoria Medal
1985 one of the inaugural CSIRO Medals for Research Achievement
1984 the inaugural Frederick White Prize by the Australian Academy of Science

Named lectures

He has been invited to deliver the following prestigious named Lectures:

2000 Lloyd Rees Memorial Lecture, Australian Academy of Science, Melbourne, ‘New drugs for influenza and other things ‘ the role of physics, chemistry, biology and business’
2000 J E Cummins OBE Memorial Oration, The Royal Society of Victoria, ‘Illuminating Life’s Molecules ‘ challenges and opportunities in the era of the human genome’
1998 Brodie Hall Lecture, CSIRO, ‘Adapt and survive – lessons from influenza viruses’
1997 Bert Halpern Lecture, University of Wollongong, ‘Influenza virus ‘ under the microscope and under attack’
1996 Pehr Edman lecture, St. Vincent’s Institute of Medical Research, ‘Designer drugs for influenza virus ‘ the role of protein chemistry in their discovery’
1996 Hartung Youth Lecture, Royal Australian Chemical Institute, ‘Influenza virus: behind the mask of the master of disguise’
1995 Foundation Lecture, University of Adelaide, Alumni association, ‘Influenza Virus ‘ behind the mask of the master of disguise’
1987 Leach Lecture, Lorne Conference on Protein Structure and Function, ‘Structure of an antibody-antigen complex’

Professional experience

2002 – 02 NHMRC Senior Principal Research Fellow
2001 – 06 Fraser Fellowship, Cancer Council of Victoria
2001- Head, Structural Biology Division, WEHI
1998 – 2008 Adjunct Professor, La Trobe University
1991 – 2000 Director, Biomolecular Research Institute
1990 – 92 Member, Board of Directors of Gene Shears Pty Ltd
1998 Professorial Fellow, University of Melbourne
1997- Founding Member, Board of Directors, Starpharma Ltd
1989 – 97 Chief, CSIRO Division of Biomolecular Engineering
1988 – 98 Professorial Associate, University of Melbourne
1985 – 91 Founding Member of the Board of Directors of Biota Holdings Ltd
1978 – 89 Officer of CSIRO at the Division of Protein Chemistry
1977 – 78 Principal Investigator, NH&MRC, University of Sydney
1977 Consultant, University of Utah
1977 EMBO Fellow, Max Planck Institute, Munich
1975 – 77 QEII Fellow, University of Sydney
1972 – 75 Post Doctoral Fellow, Max Planck Institute, Munich
1969 – 72 Post Doctoral Fellow, University of Oregon

In 1993, Time Australia ran the story ‘Through with Flu’ with Peter Colman and Mark von Itzstein (Victorian College of Pharmacy) featured on the cover.

In the 17 November 1999 issue of the London Sunday Times, Peter Colman and Graeme Laver were ranked 56th in a list of The Most Powerful People in Britain and 3rd in the Medicine list.

Sources

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