Peter Koopman

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Peter Anthony Koopman FAA (born 3 December 1959) is an Australian biologist best known for his role in the discovery and study of the mammalian Y-chromosomal sex-determining gene, Sry. [1] [2] [3] [4]

Contents

Early life and education

Peter Anthony Koopman was born on 3 December 1959 in Geelong, Victoria, to Dutch immigrant parents, and raised in the coastal town of Torquay, Victoria. He attended Oberon High School in Geelong, where he was School Captain. He studied science at the University of Melbourne from 1977 to 1979, majoring in genetics, and was a resident of Janet Clarke Hall. He undertook BSc Honours research at the Birth Defects Research Institute (now the Murdoch Children's Research Institute) at the Royal Children's Hospital, Melbourne, under the supervision of Richard (Dick) Cotton, and graduated with First Class Honours.

Continuing to work with Cotton, his PhD focused on stem cell differentiation in vitro. During this time, he also studied Japanese, Fine Arts and Dutch language and literature, receiving a BA degree from the University of Melbourne in 1985.

He was awarded a Doctor of Science (DSc) from the University of Queensland in July 2018.

Career and research

Discovery of Sry and the genetics of sex determination

In 1988, Koopman was recruited to the Medical Research Council's National Institute for Medical Research at Mill Hill, London, working first with Anne McLaren, then joining a team led by Robin Lovell-Badge to search for the Y chromosomal sex-determining gene. Koopman demonstrated that activity of mouse homologues of the existing candidate, ZFY, was not consistent with a role in sex determination. [5] Lovell-Badge's team, collaborating with Peter Goodfellow and colleagues at the Imperial Cancer Research Fund in London, discovered a new candidate gene, Sry. [1] [6] Koopman and colleagues injected Sry into fertilized XX mouse eggs which as a result developed as males, thus proving the male sex-determining role of Sry. [3] The discovery is regarded as one of the major achievements in molecular genetics in the 20th century.

Much of Koopman's subsequent research has focused on understanding how Sry acts to direct the formation of testes in the embryo, triggering male development. This work has involved the identification and/or study of a large number of other genes involved in development of the testes or ovaries. [7]

Sox genes

Establishing his own research group [8] at the University of Queensland, Brisbane, Australia in 1992, Koopman set out to discover new members of a growing family of genes related to Sry – "Sox" genes. [9] [10] Among the first discoveries was Sox9, [11] a key regulator of skeletal and testis development, which carries mutations in humans with the skeletal disorder campomelic dysplasia and associated XY sex reversal. [12]

Koopman's group also discovered Sox18, [13] [14] a switch gene that directs formation of the lymphatic vessels, [15] and is defective in humans with hypotrichosis-lymphedema-telangiectasia syndrome. [16] Given the role of lymphatic vessels in tumour metastasis, Sox18 is being developed as a potential drug target for anti-metastatic cancer therapy. [17]

Koopman found that the human and mouse genomes contain 20 Sox genes, [18] and he proposed the naming system for Sox genes that continues to be used today. [19]

Germ cell sex

Koopman's early work with Anne McLaren spawned an interest in the regulation of the germ cells during fetal development—cells that later become sperm or oocytes. [20] His group discovered that the vitamin A metabolite retinoic acid stimulates germ cells to enter meiosis, a critical step in the formation of gametes. [21] They also demonstrated that the developmental signaling molecule Nodal and its receptor Cripto regulate male germ cell pluripotency in the fetal gonad, [22] opening the way for new non-invasive diagnostics and targeted additional therapies for testicular cancers. [23]

Intersex advocacy

With a growing interest in human variations of sex development (alternatively known as DSD, differences or disorders of sex development, variations in sex characteristics, or intersex), Koopman began to engage with relevant clinicians and intersex advocacy and support groups. To cater for a need for unbiased information relating to the causes, types, impacts of DSD and options for affected people, Koopman authored a website, published under the auspices of the Australian National Health and Medical Research Council’s Research Program in Human DSD. He continues to work with the Australian Pediatric Endocrine Group and a range of advocacy groups to improve dialogue and management of these conditions. [24]

Research integrity

From 2012 to 2017, Koopman worked as the University of Queensland's Executive Director of Research Integrity, providing academic stewardship of research integrity and managing allegations of research misconduct.

Equity and diversity

Koopman co-chairs the Equity and Diversity Reference Group of the Australian Academy of Science [25] and is a member of the Women in Health Science Working Committee of NHMRC Australia, [26] and is involved in developing the Decadal Plan for Women in STEM [27] commissioned by the Australian Government.

Awards and honours

1981: First Class Honours, Department of Genetics, The University of Melbourne

1992: AMP Biomedical Research Award, Australian Society for Medical Research

1992: Australian Research Fellowship, Australian Research Council

1998: Julian Wells Medal, Lorne Genome Conference Inc [28]

2002: Australian Professorial Fellowship, Australian Research Council [29]

2003: Amersham-Pharmacia Biotech Medal, Australian Society for Biochemistry and Molecular Biology [30]

2005: President's Medal, Australia and New Zealand Society for Cell and Developmental Biology [31]

2007: Australian Professorial Fellowship, Australian Research Council [32]

2007: Award for Research Excellence, GSK Australia [33]

2008: Fellow of the Australian Academy of Science (FAA) [34]

2009: Lemberg Medal, Australian Society for Biochemistry and Molecular Biology [35]

2024: Suzanne Cory Medal, Australian Academy of Science

Other achievements

Koopman instigated the Australian Developmental Biology Workshop (2001- ), the Australian Sex Summit (2004- ), and the International Workshop on Sox Transcription Factors (2005 - ). He was organizer of the Cold Spring Harbor (USA) Workshop on Molecular Embryology of the Mouse (1995-1998), and Chair of the Gordon Research Conference on Germinal Stem Cell Biology (2017).

Koopman has trained 34 postdoctoral research staff and 28 PhD students. He has published more than 280 research papers that have been cited over 19,000 times. [36]

Related Research Articles

David C. Page is an American biologist and professor at the Massachusetts Institute of Technology (MIT), the director of the Whitehead Institute, and a Howard Hughes Medical Institute (HHMI) investigator. He is best known for his work on mapping the Y-chromosome and on its evolution in mammals and expression during development.

<span class="mw-page-title-main">Sex-determining region Y protein</span> Protein that initiates male sex determination in therian mammals

Sex-determining region Y protein (SRY), or testis-determining factor (TDF), is a DNA-binding protein encoded by the SRY gene that is responsible for the initiation of male sex determination in therian mammals. SRY is an intronless sex-determining gene on the Y chromosome. Mutations in this gene lead to a range of disorders of sex development with varying effects on an individual's phenotype and genotype.

SOX genes encode a family of transcription factors that bind to the minor groove in DNA, and belong to a super-family of genes characterized by a homologous sequence called the HMG-box. This HMG box is a DNA binding domain that is highly conserved throughout eukaryotic species. Homologues have been identified in insects, nematodes, amphibians, reptiles, birds and a range of mammals. However, HMG boxes can be very diverse in nature, with only a few amino acids being conserved between species.

<span class="mw-page-title-main">Sex cords</span> Structures that develop from the genital ridges that further differentiate based on an embryos sex

Sex cords are embryonic structures which eventually will give rise (differentiate) to the adult gonads. They are formed from the genital ridges - which will develop into the gonads - in the first 2 months of gestation which depending on the sex of the embryo will give rise to male or female sex cords. These epithelial cells penetrate and invade the underlying mesenchyme to form the primitive sex cords. This occurs shortly before and during the arrival of the primordial germ cells (PGCs) to the paired genital ridges. If there is a Y chromosome present, testicular cords will develop via the Sry gene : repressing the female sex cord genes and activating the male. If there is no Y chromosome present the opposite will occur, developing ovarian cords. Prior to giving rise to sex cords, both XX and XY embryos have Müllerian ducts and Wolffian ducts. One of these structures will be repressed to induce the other to further differentiate into the external genitalia.

<span class="mw-page-title-main">Genital ridge</span>

The genital ridge is the precursor to the gonads. The genital ridge initially consists mainly of mesenchyme and cells of underlying mesonephric origin. Once oogonia enter this area they attempt to associate with these somatic cells. Development proceeds and the oogonia become fully surrounded by a layer of cells.

Gonadal dysgenesis is classified as any congenital developmental disorder of the reproductive system characterized by a progressive loss of primordial germ cells on the developing gonads of an embryo. One type of gonadal dysgenesis is the development of functionless, fibrous tissue, termed streak gonads, instead of reproductive tissue. Streak gonads are a form of aplasia, resulting in hormonal failure that manifests as sexual infantism and infertility, with no initiation of puberty and secondary sex characteristics.

<span class="mw-page-title-main">SOX2</span> Transcription factor gene of the SOX family

SRY -box 2, also known as SOX2, is a transcription factor that is essential for maintaining self-renewal, or pluripotency, of undifferentiated embryonic stem cells. Sox2 has a critical role in maintenance of embryonic and neural stem cells.

<span class="mw-page-title-main">SOX9</span> Transcription factor gene of the SOX family

Transcription factor SOX-9 is a protein that in humans is encoded by the SOX9 gene.

<span class="mw-page-title-main">SOX4</span> Protein-coding gene in the species Homo sapiens

Transcription factor SOX-4 is a protein that in humans is encoded by the SOX4 gene.

<span class="mw-page-title-main">SOX3</span> Protein-coding gene in the species Homo sapiens

Transcription factor SOX-3 is a protein that in humans is encoded by the SOX3 gene. This gene encodes a member of the SOX family of transcription factors involved in the regulation of embryonic brain development and in determination of cell fate. The encoded protein acts as a transcriptional activator.

<span class="mw-page-title-main">SOX5</span> Protein-coding gene in Homo sapiens

Transcription factor SOX-5 is a protein that in humans is encoded by the SOX5 gene.

<span class="mw-page-title-main">SOX13</span> Protein-coding gene in the species Homo sapiens

Transcription factor SOX-13 is a protein that in humans is encoded by the SOX13 gene.

<span class="mw-page-title-main">SOX18</span> Protein-coding gene in the species Homo sapiens

Transcription factor SOX-18 is a protein that in humans is encoded by the SOX18 gene.

<span class="mw-page-title-main">SOX11</span> Protein-coding gene in the species Homo sapiens

Transcription factor SOX-11 is a protein that in humans is encoded by the SOX11 gene.

<span class="mw-page-title-main">SOX12</span> Protein-coding gene in the species Homo sapiens

SOX12 is a protein that in humans is encoded by the SOX12 gene. Sox12 belongs to the SoxC group of Sox family of transcription factors, together with Sox4 and Sox11. Sox12-null knockout mice appear normal, unlike Sox4 or Sox11 knockout mice. This probably comes from functional redundancy with Sox4 and Sox11. Sox12 is a weaker activator than both Sox4 and Sox11 in mouse.

<span class="mw-page-title-main">SOX14</span> Protein-coding gene in the species Homo sapiens

Transcription factor SOX-14 is a protein that in humans is encoded by the SOX14 gene.

<span class="mw-page-title-main">SOX21</span> Protein-coding gene in the species Homo sapiens

Transcription factor SOX-21 is a protein that in humans is encoded by the SOX21 gene. It is a member of the Sox gene family of transcription factors.

<span class="mw-page-title-main">Diethard Tautz</span> German biologist and geneticist (born 1957)

Diethard Tautz is a German biologist and geneticist, who is primarily concerned with the molecular basis of the evolution of mammals. Since 2006 he is director at the Max Planck Institute for Evolutionary Biology in Plön.

<span class="mw-page-title-main">Elizabeth Robertson</span> British geneticist

Elizabeth Jane Robertson is a British developmental biologist based at the Sir William Dunn School of Pathology, University of Oxford. She is Professor of Developmental Biology at Oxford and a Wellcome Trust Principal Research Fellow. She is best known for her pioneering work in developmental genetics, showing that genetic mutations could be introduced into the mouse germ line by using genetically altered embryonic stem cells. This discovery opened up a major field of experimentation for biologists and clinicians.

Emily Bernstein is a professor at Mount Sinai School of Medicine known for her research on RNA interference, epigenetics, and cancer, especially melanoma.

References

  1. 1 2 Gubbay, John; Collignon, Jérôme; Koopman, Peter; Capel, Blanche; Economou, Androulla; Münsterberg, Andrea; Vivian, Nigel; Goodfellow, Peter; Lovell-Badge, Robin (July 1990). "A gene mapping to the sex-determining region of the mouse Y chromosome is a member of a novel family of embryonically expressed genes". Nature. 346 (6281): 245–250. Bibcode:1990Natur.346..245G. doi:10.1038/346245a0. ISSN   0028-0836. PMID   2374589. S2CID   4270188.
  2. ↑ Koopman, Peter; Münsterberg, Andrea; Capel, Blanche; Vivian, Nigel; Lovell-Badge, Robin (November 1990). "Expression of a candidate sex-determining gene during mouse testis differentiation". Nature. 348 (6300): 450–452. Bibcode:1990Natur.348..450K. doi:10.1038/348450a0. ISSN   0028-0836. PMID   2247150. S2CID   4322050.
  3. 1 2 Koopman, Peter; Gubbay, John; Vivian, Nigel; Goodfellow, Peter; Lovell-Badge, Robin (May 1991). "Male development of chromosomally female mice transgenic for Sry". Nature. 351 (6322): 117–121. Bibcode:1991Natur.351..117K. doi:10.1038/351117a0. ISSN   0028-0836. PMID   2030730. S2CID   3331979.
  4. ↑ The University of Queensland. "UQ Researchers".
  5. ↑ Koopman, Peter; Gubbay, John; Collignon, Jérôme; Lovell-Badge, Robin (December 1989). "Zfy gene expression patterns are not compatible with a primary role in mouse sex determination". Nature. 342 (6252): 940–942. Bibcode:1989Natur.342..940K. doi:10.1038/342940a0. ISSN   0028-0836. PMID   2480529. S2CID   4303582.
  6. ↑ Sinclair, Andrew H.; Berta, Philippe; Palmer, Mark S.; Hawkins, J. Ross; Griffiths, Beatrice L.; Smith, Matthijs J.; Foster, Jamie W.; Frischauf, Anna-Maria; Lovell-Badge, Robin (July 1990). "A gene from the human sex-determining region encodes a protein with homology to a conserved DNA-binding motif". Nature. 346 (6281): 240–244. Bibcode:1990Natur.346..240S. doi:10.1038/346240a0. ISSN   0028-0836. PMID   1695712. S2CID   4364032.
  7. ↑ "UQ eSpace". espace.library.uq.edu.au. Retrieved 10 October 2018.
  8. ↑ "Institute for Molecular Bioscience - University of Queensland". Institute for Molecular Bioscience. Retrieved 10 October 2018.
  9. ↑ Wright, Edwina M.; Snopek, Bernadette; Koopman, Peter (1993). "Seven new members of theSoxgene family expressed during mouse development". Nucleic Acids Research. 21 (3): 744. doi:10.1093/nar/21.3.744. ISSN   0305-1048. PMC   309180 . PMID   8441686.
  10. ↑ Koopman P, Bullejos M, Bowles J. (2001). "Regulation of male sexual development by Sry and Sox9". Journal of Experimental Zoology. 290 (5): 463–474. doi:10.1002/jez.1089. PMID   11555853.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  11. ↑ Wright, Edwina; Hargrave, Murray R.; Christiansen, Jeffrey; Cooper, Leanne; Kun, Jutta; Evans, Timothy; Gangadharan, Uma; Greenfield, Andy; Koopman, Peter (January 1995). "The Sry-related gene Sox9 is expressed during chondrogenesis in mouse embryos". Nature Genetics. 9 (1): 15–20. doi:10.1038/ng0195-15. ISSN   1061-4036. PMID   7704017. S2CID   22654180.
  12. ↑ Foster, Jamie W.; Dominguez-Steglich, Marina A.; Guioli, Silvana; Kwok, Cheni; Weller, Polly A.; Stevanović, Milena; Weissenbach, Jean; Mansour, Sahar; Young, Ian D. (December 1994). "Campomelic dysplasia and autosomal sex reversal caused by mutations in an SRY-related gene". Nature. 372 (6506): 525–530. Bibcode:1994Natur.372..525F. doi:10.1038/372525a0. ISSN   0028-0836. PMID   7990924. S2CID   1472426.
  13. ↑ Hosking, Brett M.; Muscat, George E.O.; Koopman, Peter A.; Dowhan, Dennis H.; Dunn, Timothy L. (1995). "Trans-activation and DNA-binding properties of the transcription factor, Sox-18". Nucleic Acids Research. 23 (14): 2626–2628. doi:10.1093/nar/23.14.2626. ISSN   0305-1048. PMC   307084 . PMID   7651823.
  14. ↑ Pennisi, David; Gardner, Jennifer; Chambers, Doreen; Hosking, Brett; Peters, Josephine; Muscat, George; Abbott, Catherine; Koopman, Peter (April 2000). "Mutations in Sox18 underlie cardiovascular and hair follicle defects in ragged mice". Nature Genetics. 24 (4): 434–437. doi:10.1038/74301. ISSN   1061-4036. PMID   10742113. S2CID   24013687.
  15. ↑ François, Mathias; Caprini, Andrea; Hosking, Brett; Orsenigo, Fabrizio; Wilhelm, Dagmar; Browne, Catherine; Paavonen, Karri; Karnezis, Tara; Shayan, Ramin (19 October 2008). "Sox18 induces development of the lymphatic vasculature in mice". Nature. 456 (7222): 643–647. Bibcode:2008Natur.456..643F. doi:10.1038/nature07391. ISSN   0028-0836. PMID   18931657. S2CID   4416082.
  16. ↑ Irrthum, Alexandre; Devriendt, Koenraad; Chitayat, David; Matthijs, Gert; Glade, Conrad; Steijlen, Peter M.; Fryns, Jean-Pierre; Van Steensel, Maurice A. M.; Vikkula, Miikka (June 2003). "Mutations in the Transcription Factor Gene SOX18 Underlie Recessive and Dominant Forms of Hypotrichosis-Lymphedema-Telangiectasia". The American Journal of Human Genetics. 72 (6): 1470–1478. doi:10.1086/375614. ISSN   0002-9297. PMC   1180307 . PMID   12740761.
  17. ↑ Overman, Jeroen; Fontaine, Frank; Moustaqil, Mehdi; Mittal, Deepak; Sierecki, Emma; Sacilotto, Natalia; Zuegg, Johannes; Robertson, Avril AB; Holmes, Kelly (31 January 2017). "Pharmacological targeting of the transcription factor SOX18 delays breast cancer in mice". eLife. 6. doi: 10.7554/elife.21221 . ISSN   2050-084X. PMC   5283831 . PMID   28137359.
  18. ↑ Schepers, Goslik E.; Teasdale, Rohan D.; Koopman, Peter (August 2002). "Twenty Pairs of Sox". Developmental Cell. 3 (2): 167–170. doi: 10.1016/s1534-5807(02)00223-x . ISSN   1534-5807. PMID   12194848.
  19. ↑ Bowles, Josephine; Schepers, Goslik; Koopman, Peter (November 2000). "Phylogeny of the SOX Family of Developmental Transcription Factors Based on Sequence and Structural Indicators". Developmental Biology. 227 (2): 239–255. doi: 10.1006/dbio.2000.9883 . ISSN   0012-1606. PMID   11071752.
  20. ↑ Koopman P. (2016). "The Curious World of Gonadal Development in Mammals". Current Topics in Developmental Biology. 116: 537–545. doi:10.1016/bs.ctdb.2015.12.009. ISBN   9780128029565. PMID   26970639.
  21. ↑ Bowles, Josephine; Knight, Deon; Smith, Christopher; Wilhelm, Dagmar; Richman, Joy; Mamiya, Satoru; Yashiro, Kenta; Chawengsaksophak, Kallayanee; Wilson, Megan J. (28 April 2006). "Retinoid Signaling Determines Germ Cell Fate in Mice". Science. 312 (5773): 596–600. Bibcode:2006Sci...312..596B. doi:10.1126/science.1125691. ISSN   0036-8075. PMID   16574820. S2CID   2514848.
  22. ↑ Spiller, Cassy M.; Feng, Chun-Wei; Jackson, Andrew; Gillis, Ad J. M.; Rolland, Antoine D.; Looijenga, Leendert H. J.; Koopman, Peter; Bowles, Josephine (15 November 2012). "Endogenous Nodal signaling regulates germ cell potency during mammalian testis development". Development. 139 (22): 4123–4132. doi: 10.1242/dev.083006 . ISSN   0950-1991. PMID   23034635.
  23. ↑ Spiller, Cassy M.; Bowles, Josephine; Koopman, Peter (2013). "Nodal/Cripto signaling in fetal male germ cell development: implications for testicular germ cell tumors". The International Journal of Developmental Biology. 57 (2–3–4): 211–219. doi: 10.1387/ijdb.130028pk . ISSN   0214-6282. PMID   23784832.
  24. ↑ Lee, Peter A.; Nordenström, Anna; Houk, Christopher P.; Ahmed, S. Faisal; Auchus, Richard; Baratz, Arlene; Baratz Dalke, Katharine; Liao, Lih-Mei; Lin-Su, Karen (2016). "Global Disorders of Sex Development Update since 2006: Perceptions, Approach and Care". Hormone Research in Paediatrics. 85 (3): 158–180. doi: 10.1159/000442975 . ISSN   1663-2818. PMID   26820577.
  25. ↑ "Committee—Equity and Diversity Reference Group | Australian Academy of Science". www.science.org.au. Retrieved 10 October 2018.
  26. ↑ "Women in health science working committee". National Health and Medical Research Council.
  27. ↑ "Women in Science, Technology, Engineering and Mathematics (STEM) Decadal Plan | Australian Academy of Science". www.science.org.au. Retrieved 10 October 2018.
  28. ↑ "UQ researcher wins medal for excellence in gene research". UQ News. Retrieved 10 October 2018.
  29. ↑ "Molecular genetics of mammalian sexual development: Molecular roles of SRY and SOX9 - UQ Researchers". researchers.uq.edu.au. Retrieved 10 October 2018.
  30. ↑ "2002 Amersham Pharmacia Biotech Medallist: Professor Peter Koopman". Australian Society for Biochemistry and Molecular Biology. Retrieved 10 October 2018.
  31. ↑ "President's Medal » ANZSCDB". www.anzscdb.org. Retrieved 10 October 2018.
  32. ↑ "How the Y Chromosome makes a male: Molecular genetic analysis of key sex-determining genes - UQ Researchers". researchers.uq.edu.au. Retrieved 10 October 2018.
  33. ↑ "Alumni Members | GSK Australia" . Retrieved 10 October 2018.
  34. ↑ "Professor Peter Anthony Koopman | Australian Academy of Science". www.science.org.au. Retrieved 10 October 2018.
  35. ↑ "Peter Koopman - ASBMB". ASBMB. Retrieved 10 October 2018.
  36. ↑ ORCID. "Peter Koopman (0000-0001-6939-0914) - ORCID | Connecting Research and Researchers". orcid.org. Retrieved 10 October 2018.
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