User:Neuraustralia/sandbox
Peter Schofield | |
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| Born | Peter Robert Schofield 11 September 1959 |
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| Spouse | Katharine Schofield |
| Children | Christopher, Timothy and Benjamin |
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| Website | neura |
Peter R Schofield BScAgr (Hons1) (USyd), PhD (ANU), DSc (UNSW), is an eminent Australian medical researcher, Professor of Medicine at the University of New South Wales, and current Executive Director and CEO of NeuRA - Neuroscience Research Australia.
Schofield graduated from Sydney University in 1982 with First Class Honours and the University Medal from the Faculty of Agriculture having majored in genetics. He undertook his PhD studies in molecular genetics at the Australian National University graduating in 1985. Following a brief competitive postdoctoral fellowship at CSIRO Plant Industry he moved to the US to undertake a postdoctoral fellowship with Peter Seeburg at the leading US biotechnology company Genentech Inc where he redirected the focus of his research career to molecular neuroscience. Here he worked on the molecular cloning and characterisation of neurotransmitter receptors and enzymes, work that was subsequently continued and expanded at the Centre for Molecular Biology at the University of Heidelberg, Germany.
He returned to Australia, initially working at the biotech start-up Pacific Biotechnology Ltd and commenced at the Garvan Institute in 1991, being appointed a Senior Research Fellow. In 1993 he was appointed to the NHMRC Research Fellowship scheme, as a NHMRC Senior Research Fellow and was subsequently promoted to NHMRC Principal Research Fellow in 1997 and NHMRC Senior Principal Research Fellow in 2001. He was appointed as Head of the Neurobiology Research Program at the Garvan Institute in 1999. He commenced his current position as Executive Director and CEO at NeuRA - Neuroscience Research Australia (previously Prince of Wales Medical Research Institute) in 2004. He has had an academic association with the School of Biotechnology and the Schools of Medicine/Medical Sciences at the University of New South Wales since 1993 and was appointed adjunct Associate Professor in 1996 and Professor in 2000. In 1998, he was awarded the degree of Doctor of Science by the University of New South Wales for his body of published work on molecular neuroscience.
Research and Citation Record
[edit]His research has fundamentally altered the understanding of neurotransmitter signaling and has identified the role of genes that lead to neurodegenerative and psychiatric disorders such as Alzheimer's disease and bipolar disorder. His major research achievements in neuroscience have been in four key areas: i) His cloning of the genes encoding neurotransmitter receptors defined the primary structures, revealed the existence of receptor superfamilies and illuminated molecular, functional and anatomical receptor subtype diversity; ii) Using the glycine receptor as a model, he identified and mapped the ligand-binding domains of the receptor and together with his studies of heritable mutations have contributed to our understanding of signal transduction and ion permeation; iii) His use of genetic approaches to define the genes that cause Alzheimer’s disease and frontotemporal dementia has provided key insights into phenotypic variability and led to the discovery of genes causing dementia and correlation with disease biomarkers; and iv) He has developed research programs to identify and characterise risk-factor genes that contribute to both normal brain function and underpin the development of psychiatric disorders, especially bipolar disorder. He has an outstanding research record and has built a genuine international reputation in molecular neurobiology, neurogenetics and the genetics of psychiatric diseases. He has published over 290 papers.
Contributions to the Profession and broader Community
[edit]He has made substantial professional and community contributions, including as a Director and President of The Australian Society of Medical Research, a Foundation Director of Research Australia and as a member of the Lockhart Review Committee that examined stem cell research in Australia and whose recommendations were adopted by the Federal and State Governments. As CEO of NeuRA, Peter has led the expansion of the research agenda to include both the development of programs in molecular, cellular and genetic research and the development of programs in psychiatric and psychological research. NeuRA is thus one of the few global neuroscience research centres which effectively maintains both a strong clinical and basic research focus. Peter led the rebranding of the institute to then now NeuRA with a tag-line ‘Discover, Conquer, Cure’ to effectively communicate to researchers and the public how NeuRA focuses and applies its research efforts. Over the period of his leadership Peter has conceived and delivered the design, funding, construction and occupancy of the Neuroscience Research Precinct, a multi-stage, state-of-the-art research facility on the Prince of Wales Hospital campus at Randwick. This precinct development aims to physically, philosophically and operationally enhance research linkages and to contribute to the more effective translation of research outcomes to improved health and well-being. The first stage, the 8,165m2 Margarete Ainsworth Building was completed in December 2012 and was officially opened on 23 July 2013 by (then) Minister Tanya Plibersek and Minister Jillian Skinner. The precinct, once fully developed, will provide six stories of research space, 25,470m2 floor space and be able to house up to 700 researchers.
Leadership in promoting health and medical research
[edit]He has an outstanding commitment to supporting Australian health and medical research, and is an articulate advocate for medical research among the scientific and the general community. He served 5 years as Director and President of the Australian Society for Medical Research (ASMR), the national researcher body that fosters and advocates for health and medical research. ASMR plays a major role in lobbying the government to provide adequate and sustained funding for health and medical research. As President Elect and President, he was instrumental in the establishment of the inaugural ASMR Health and Medical Research Congress as well as the establishment of Research Australia. He was a Steering Committee member and Foundation Director of Research Australia, an initiative arising from the Australian Government’s Wills Review. This national body of Australian organisations and companies is committed to making health and medical research a higher national priority. The organisation is unique in that it has attracted members from outside the research sector who share the common goals of promoting awareness, investment, and informing the community about the value and benefits of health and medical research. As a Member of the Prime Minister's Science, Engineering and Innovation Council (PMSEIC) Working Group, Professor Schofield was a key contributor to the report “Brain and Mind Disorders: Impact of the Neurosciences”. The Government took a positive stance in responding to this report by establishing a Neuroscience Consultative Task Force, whereupon Peter joined this group at the invitation of then Health Minister Tony Abbott. The report showed that brain and mind disorders pose the highest health, economic and social capital attrition burden to Australia of any disease group. This advocacy role was continued through NeuroScience Australia (NSA), a national body which developed and lobbied for a national neuroscience initiative. At a State level, Peter was a member of the Reference Group led by the NSW Director General of the Ministry of Science and Medical Research, playing a key role in the development of the NSW Medical Research Strategy. In 2005, Peter was one of six members appointed by then Federal Minister for Ageing Julie Bishop to the Legislation Review Committee led by Justice John Lockhart AO to review the Prohibition of Human Cloning Act 2002 & Research Involving Human Embryos Act 2002. Following the untimely death of Justice Lockhart and the government’s proposal to not adopt the changes, Peter was one of the most active Committee Members in supporting Federal and State Parliamentarians in reviewing the report and especially in terms of advising about the specific details for inclusion in the proposed legislation. This included extensive engagement with Senator Kay Patterson (a former Health Minister) who sponsored a Private Members Bill and Senator Natasha Stott-Despoja who sponsored an exposure draft. The Review’s report and recommendations formed the basis of Senator Patterson’s Private Members Bill which was passed as the “Prohibition of Human Cloning for Reproduction and the Regulation of Human Embryo Research Amendment Act 2006” in December 2006. Following adoption of the Federal legislation, each of the State Governments also developed legislation. Again, Peter was heavily engaged in parliamentary briefing sessions and advising the Ministers sponsoring this legislation, The Hon Verity Firth in NSW and The Hon Lara Giddings in Tasmania. His involvement in this controversial and ethically charged area also led to many professional and community contributions, an invited commentary published in Cell and a Research Australia Media Award in 2006. Most recently he has led scientific advocacy from the research community to government in the recently funded Dementia Research Initiative. Other professional service and advocacy activities have included roles as a Director and President of the Genome Conference Inc (1994-2004), Secretary and Chairman of the St Vincent’s Institutional Biosafety Committee (1992-2004) and serving for a decade (1995-2005) as a member of the Pharmaceutical Sub-Committee of the Australian Drug Evaluation Committee. He was a member of the Reference Group for the NSW Medical Research Strategy in 2004/5. He was a foundation member of the Australasian Course for Advanced Neuroscience held on North Stradbroke Island since 2005, and has Chaired the Selection Committee of the NSW Young Tall Poppies Campaign from 2007-2010 and in 2011 was appointed a member of National Committee for Medicine, Australian Academy of Science and has chaired the committee from late 2014.
Most Significant Publications
[edit]1.) Sequence and functional expression of the GABAA receptor shows a ligand-gated receptor superfamily. Schofield, P.R., Darlison, M. G., Fujita, N. Burt, D. R., Stephenson, F. A. Rhee, L. M., Rodriguez, H., Ramachandran, J., Glencorse, T.A., Reale, V. Seeburg, P.H. and Barnard, E.A. (1987) Nature 328: 221-227.
Contribution - Schofield cloned the α1 and β subunits of the major inhibitory neurotransmitter receptor, the gamma-aminobutyric acid type A receptor (GABAA R). In addition to defining the primary structure of this important neuroreceptor, this work revealed the existence of the ligand-gated ion channel (Cys-loop) receptor superfamily. This ‘article’ publication in Nature included the cover illustration and an editorial and has become standard textbook material.
2.) Structural and functional basis for GABAA receptor heterogeneity. Levitan ES,* Schofield PR,* Burt DR, Rhee LM, Wisden W, Koehler M, Fujita N, Rodriguez H, Stephenson FA, Darlison MG, Barnard EA and Seeburg PH. (1988) Nature 335: 76-79. * ESL & PRS are equal first authors.
Contribution - Schofield cloned the first of multiple GABAA R subunit subtypes, and collaborative expression studies demonstrated that receptor heterogeneity at the molecular level resulted in receptors with differing biological properties, e.g. differences in agonist sensitivity (Nature, 604 citations). Additional studies cloning and characterising additional GABAA R subunits showed that receptor subtype heterogeneity was a common feature of the Cys-loop receptor superfamilies and led to three EMBO Journal papers with 428, 237 and 230 citations, respectively.
3.) Transient expression shows ligand gating and allosteric potentiation of GABAA receptor subunits. Pritchett DB, Sontheimer H, Gorman CM, Kettenmann H, Seeburg PH and Schofield PR. (1988) Science 242: 1306-1308.
Contribution - Schofield conceived and directed this study in which the recently developed transient mammalian cell expression system comprising the CMV promoter and human embryonic kidney 293 cell assay system was used for the electrophysiological analysis of ion channels and receptors. This clear demonstration of utility has formed the basis of thousands of subsequent expression and electrophysyiological analyses by laboratories from around the world.
4.) Importance of a novel GABAA receptor subunit for benzodiazepine pharmacology. Pritchett, D.B., Sontheimer, H., Shivers, B.D., Ymer, S., Kettenmann, H., Schofield, P.R. and Seeburg, P.H. (1989) Nature 338: 582-585.
Contribution - The identification and analysis of novel receptor subunits, cloned and sequenced by Schofield as prevailing dogma described GABAA Rs as containing only α and β subunits. Using mammalian cell expression systems, conceived by Schofield, he and his colleagues showed that the γ subunits, in particular the γ2 subunit, mediated the benzodiazepine response. This ‘letter’ paper in Nature represents the conciseness and brevity that can accompany a far-reaching discovery.
5.) Two novel GABAA receptor subunits exist in distinct neuronal subpopulations. Shivers BD, Killisch I, Sprengel R, Sontheimer H, Koehler M, Schofield PR and Seeburg PH. (1989) Neuron 3: 327-337.
Contribution - The functional heterogeneity of GABAA Rs far exceeded that previously conceived as demonstrated in this study in which Schofield conceived the ideas and cloned the new γ2 and δ subunits. The anatomical distribution of receptor subunits showed distinct and non-overlapping expression in neuronal subpopulations. This was significant as many had speculated that the number of possible receptor combinations would be extremely large, whereas this study showed that receptor subtype heterogeneity was a new but tractable phenomenon.
6.) Mutation of an arginine residue in the human glycine receptor transforms β-alanine and taurine from agonists into competitive antagonists. Rajendra S, Lynch JW, Pierce KD, French CR, Barry PH and Schofield PR. (1995) Neuron 14: 169-175.
Contribution – Arising from his laboratories work at the Garvan Institute, Peter established an internationally recognised research program describing the mechanisms of ligand-binding, signal transduction and ion permeation using the homomeric Gly R. Studies of the functional consequences of the human hyperekplexia disease causing mutations led to unexpected insights into the mechanisms by which the Gly R and other Cys-loop receptors transduce ligand binding into ion channel activation.
7.) A missense mutation in the gene encoding the α1 subunit of the inhibitory glycine receptor in the spasmodic mouse. Ryan SG, Buckwalter MS, Lynch JW, Handford CA, Segura L, Shiang R, Wasmuth JJ, Camper SA, Schofield P and O'Connell, P. (1994) Nature Genetics 7: 131-135.
Contribution – This collaborative study with Dr Stephen Ryan commenced a long series of studies using mouse and bovine animal models to better understand and characterise the molecular mechanisms of Glycine Receptor activation and signalling.
8.) Identification of intracellular and extracellular domains mediating signal transduction in the inhibitory glycine receptor chloride channel. Lynch JW, Rajendra S, Pierce KD, Handford CA, Barry PH and Schofield PR. (1997) The EMBO Journal 16: 110-120.
Contribution – Building on his earlier studies of the functional consequences of the human hyperekplexia disease causing mutations and followed up with extensive structure-function studies, this paper led to new insights into the mechanisms by which the Gly R and other Cys-loop receptors transduce ligand binding into ion channel activation. In this study Schofield et al identified both intracellular and extracellular loops of the Gly R α1 subunit as both playing a key role in receptor activation.