Merlin Crossley

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Merlin Crossley, AM [1] is an Australian molecular biologist, university teacher and administrator. He is Deputy Vice-Chancellor (DVC) Academic Quality and Acting DVC Research and Enterprise at the University of New South Wales. [2]

Contents

Early life and career

Crossley attended Mount View Primary School, Glen Waverley, Victoria, then was awarded an entrance scholarship to Melbourne Grammar School, where he was dux. He undertook a Bachelor of Science at the University of Melbourne, as a resident of Queen's College (University of Melbourne), then a doctorate at the University of Oxford supported by a Rhodes Scholarship at Magdalen College, Oxford. [3] He worked at Oxford, Harvard and the University of Sydney, before moving to UNSW as Dean of Science. [4] In recognition of his service on the Trust of the Australian Museum a new species of butterfly bobtail squid was named in his honour - Iridoteuthis merlini - Merlin's bobtail squid. [5] [6]

Research

Crossley is interested in gene regulation. He studied an unusual genetic disorder termed Haemophilia B Leyden where patients recover after puberty. [7] The condition results from mutations that disrupt the control region of the clotting factor IX gene. [8] [9] A testosterone-responsive element accounts for post-pubertal recovery. [10] He has also investigated abnormal patterns of globin gene expression and his work on mutations associated with the lifelong expression of the foetal haemoglobin gene may help in the treatment of thalassemia and sickle cell anaemia. [11] He is using CRISPR-mediated gene editing to introduce beneficial mutations in cell lines as models for treating genetic diseases. [12] [13] Clinical trials by major gene editing companies are now introducing mutations that his lab described.

He is also known for the initial identification and cloning of a significant number of genes encoding DNA-binding proteins and their associated co-regulators, KLF3, [14] KLF8, [15] KLF17, [16] EOS IKZF4, [17] PEGASUS IKZF5, [18] FOG1 ZFPM1, [19] FOG2 ZFPM2, [20] and CTBP2. [21]

Other activities

He has contributed numerous articles on molecular genetics and education to newspapers and media outlets such as The Conversation (website) [22] and has promoted science communication, for instance as a member of the judging panel for the annual anthology, Best Australian Science Writing. [23] He is Deputy Director of the Australian Science Media Centre (AusSMC), [24] has served on the Trust of the Australian Museum 2012-20 [25] and the Board of the Sydney Institute of Marine Science 2010-15, [26] and is on the Board of, and Chair of the Editorial Board of The Conversation (website).

Honours and awards

Related Research Articles

<span class="mw-page-title-main">Transcription factor</span> Protein that regulates the rate of DNA transcription

In molecular biology, a transcription factor (TF) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The function of TFs is to regulate—turn on and off—genes in order to make sure that they are expressed in the desired cells at the right time and in the right amount throughout the life of the cell and the organism. Groups of TFs function in a coordinated fashion to direct cell division, cell growth, and cell death throughout life; cell migration and organization during embryonic development; and intermittently in response to signals from outside the cell, such as a hormone. There are 1500-1600 TFs in the human genome. Transcription factors are members of the proteome as well as regulome.

<span class="mw-page-title-main">Haemophilia B</span> Genetic X-linked recessive bleeding disorder

Haemophilia B, also spelled hemophilia B, is a blood clotting disorder causing easy bruising and bleeding due to an inherited mutation of the gene for factor IX, and resulting in a deficiency of factor IX. It is less common than factor VIII deficiency.

<span class="mw-page-title-main">Three prime untranslated region</span> Sequence at the 3 end of messenger RNA that does not code for product

In molecular genetics, the three prime untranslated region (3′-UTR) is the section of messenger RNA (mRNA) that immediately follows the translation termination codon. The 3′-UTR often contains regulatory regions that post-transcriptionally influence gene expression.

<span class="mw-page-title-main">Factor VIII</span> Blood-clotting protein

Factor VIII (FVIII) is an essential blood-clotting protein, also known as anti-hemophilic factor (AHF). In humans, factor VIII is encoded by the F8 gene. Defects in this gene result in hemophilia A, an X-linked coagulation disorder. Factor VIII is produced in the liver’s sinusoidal cells and endothelial cells outside the liver throughout the body. This protein circulates in the bloodstream in an inactive form, bound to another molecule called von Willebrand factor, until an injury that damages blood vessels occurs. In response to injury, coagulation factor VIII is activated and separates from von Willebrand factor. The active protein interacts with another coagulation factor called factor IX. This interaction sets off a chain of additional chemical reactions that form a blood clot.

In molecular biology, the TATA box is a sequence of DNA found in the core promoter region of genes in archaea and eukaryotes. The bacterial homolog of the TATA box is called the Pribnow box which has a shorter consensus sequence.

<span class="mw-page-title-main">Factor IX</span> Protein involved in blood clotting in humans

Factor IX is one of the serine proteases of the coagulation system; it belongs to peptidase family S1. Deficiency of this protein causes haemophilia B. It was discovered in 1952 after a young boy named Stephen Christmas was found to be lacking this exact factor, leading to haemophilia.

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

Adenomatous polyposis coli (APC) also known as deleted in polyposis 2.5 (DP2.5) is a protein that in humans is encoded by the APC gene. The APC protein is a negative regulator that controls beta-catenin concentrations and interacts with E-cadherin, which are involved in cell adhesion. Mutations in the APC gene may result in colorectal cancer and desmoid tumors.

<span class="mw-page-title-main">GATA1</span> Protein-coding gene in humans

GATA-binding factor 1 or GATA-1 is the founding member of the GATA family of transcription factors. This protein is widely expressed throughout vertebrate species. In humans and mice, it is encoded by the GATA1 and Gata1 genes, respectively. These genes are located on the X chromosome in both species.

In molecular genetics, the Krüppel-like family of transcription factors (KLFs) are a set of eukaryotic C2H2 zinc finger DNA-binding proteins that regulate gene expression. This family has been expanded to also include the Sp transcription factor and related proteins, forming the Sp/KLF family.

<span class="mw-page-title-main">Autoimmune regulator</span> Immune system protein

The autoimmune regulator (AIRE) is a protein that in humans is encoded by the AIRE gene. It is a 13kb gene on chromosome 21q22.3 that has 545 amino acids. AIRE is a transcription factor expressed in the medulla of the thymus. It is part of the mechanism which eliminates self-reactive T cells that would cause autoimmune disease. It exposes T cells to normal, healthy proteins from all parts of the body, and T cells that react to those proteins are destroyed.

<span class="mw-page-title-main">Steroidogenic factor 1</span> Protein-coding gene in humans

The steroidogenic factor 1 (SF-1) protein is a transcription factor involved in sex determination by controlling the activity of genes related to the reproductive glands or gonads and adrenal glands. This protein is encoded by the NR5A1 gene, a member of the nuclear receptor subfamily, located on the long arm of chromosome 9 at position 33.3. It was originally identified as a regulator of genes encoding cytochrome P450 steroid hydroxylases, however, further roles in endocrine function have since been discovered.

<span class="mw-page-title-main">RUNX1</span> Protein-coding gene in humans

Runt-related transcription factor 1 (RUNX1) also known as acute myeloid leukemia 1 protein (AML1) or core-binding factor subunit alpha-2 (CBFA2) is a protein that in humans is encoded by the RUNX1 gene.

<span class="mw-page-title-main">Homeobox protein MSX-1</span> Protein-coding gene in the species Homo sapiens

Homeobox protein MSX-1, is a protein that in humans is encoded by the MSX1 gene. MSX1 transcripts are not only found in thyrotrope-derived TSH cells, but also in the TtT97 thyrotropic tumor, which is a well differentiated hyperplastic tissue that produces both TSHß- and a-subunits and is responsive to thyroid hormone. MSX1 is also expressed in highly differentiated pituitary cells which until recently was thought to be expressed exclusively during embryogenesis. There is a highly conserved structural organization of the members of the MSX family of genes and their abundant expression at sites of inductive cell–cell interactions in the embryo suggest that they have a pivotal role during early development.

<span class="mw-page-title-main">ZEB1</span> Protein-coding gene in the species Homo sapiens

Zinc finger E-box-binding homeobox 1 is a protein that in humans is encoded by the ZEB1 gene.

<span class="mw-page-title-main">KDM5A</span> Protein-coding gene in the species Homo sapiens

Lysine-specific demethylase 5A is an enzyme that in humans is encoded by the KDM5A gene.

<span class="mw-page-title-main">KLF8</span> Protein-coding gene in the species Homo sapiens

Krueppel-like factor 8 is a protein that in humans is encoded by the KLF8 gene. KLF8 belongs to the family of KLF protein. KLF8 is activated by KLF1 along with KLF3 while KLF3 represses KLF8.

<span class="mw-page-title-main">RIT1</span> Protein-coding gene in the species Homo sapiens

GTP-binding protein Rit1 is a protein that in humans is encoded by the RIT1 gene.

<span class="mw-page-title-main">KLF3</span> Protein-coding gene in the species Homo sapiens

Krüppel-like factor 3 is a protein that in humans is encoded by the KLF3 gene.

George Gow Brownlee FRS FMedSci is a British pathologist and Fellow of Lincoln College, Oxford.

Peter Anthony Koopman is an Australian biologist best known for his role in the discovery and study of the mammalian Y-chromosomal sex-determining gene, Sry.

References

  1. ↑ "UNSW community recognised in 2023 King's Birthday Honours". Sydney: UNSW.
  2. ↑ "Merlin Crossley". unsw.edu.au. 19 February 2016.
  3. ↑ "Rhodes Scholars: Complete List, 1903-2013". Archived from the original on 6 November 2013. Retrieved 2 May 2014.
  4. ↑ "Merlin Crossley reappointed Science Dean". UNSW Sydney. 14 January 2014.
  5. ↑ "New species of bobtail squid named in honour of Professor Merlin Crossley". 3 August 2021. Retrieved 7 August 2021.
  6. ↑ "Fire shooting 'butterfly bobtail' named in honour of Professor Merlin Crossley!" . Retrieved 7 August 2021.
  7. ↑ Funnell, AP; Crossley, M (January 2014). "Hemophilia B Leyden and once mysterious cis-regulatory mutations". Trends in Genetics. 30 (1): 18–23. doi:10.1016/j.tig.2013.09.007. PMID   24138812.
  8. ↑ Crossley, M; Brownlee, GG (May 1990). "Disruption of a C/EBP binding site in the factor IX promoter is associated with haemophilia B". Nature. 345 (6274): 444–6. Bibcode:1990Natur.345..444C. doi:10.1038/345444a0. PMID   2342576. S2CID   4261499.
  9. ↑ Funnell, AP; Wilson, MD; Ballester, B; Mak, KS; Burdach, J; Magan, N; Pearson, RC; Lemaigre, FP; Stowell, KM; Odom, DT; Flicek, P; Crossley, M (March 2013). "A CpG mutational hotspot in a ONECUT binding site accounts for the prevalent variant of hemophilia B Leyden". American Journal of Human Genetics. 92 (3): 460–7. doi:10.1016/j.ajhg.2013.02.003. PMC   3591849 . PMID   23472758.
  10. ↑ Crossley, M; Ludwig, M; Stowell, KM; De Vos, P; Olek, K; Brownlee, GG (July 1992). "Recovery from hemophilia B Leyden: an androgen-responsive element in the factor IX promoter". Science. 257 (5068): 377–9. Bibcode:1992Sci...257..377C. doi:10.1126/science.1631558. PMID   1631558.
  11. ↑ Wienert, B; Funnell, AP; Norton, LJ; Pearson, RC; Wilkinson-White, LE; Lester, K; Vadolas, J; Porteus, MH; Matthews, JM; Quinlan, KG; Crossley, M (May 2015). "Editing the genome to introduce a beneficial naturally occurring mutation associated with increased fetal globin". Nature Communications. 6 (7085): 377–9. Bibcode:2015NatCo...6.7085W. doi: 10.1038/ncomms8085 . PMID   25971621.
  12. ↑ "Turning the tables: using genetic mutations to fix nature's problems". theconversation.com. 13 May 2015.
  13. ↑ "Crossley Lab UNSW Science". unsw.edu.au.
  14. ↑ Crossley, M; Whitelaw, E; Perkins, A; Williams, G; Fujiwara, Y; Orkin, SH (April 1996). "Isolation and characterization of the cDNA encoding BKLF/TEF-2, a major CACCC-box-binding protein in erythroid cells and selected other cells" (PDF). Mol. Cell. Biol. 16 (4): 1695–705. doi:10.1128/mcb.16.4.1695. PMC   231156 . PMID   8657145.
  15. ↑ van Vliet, J; Turner, J; Crossley, M (May 2000). "Human Krüppel-like factor 8: a CACCC-box binding protein that associates with CtBP and represses transcription". Nucleic Acids Research. 28 (9): 1955–62. doi:10.1093/nar/28.9.1955. PMC   103308 . PMID   10756197.
  16. ↑ van Vliet, J; Crofts, LA; Quinlan, KG; Czolij, R; Perkins, AC; Crossley, M (April 2006). "Human KLF17 is a new member of the Sp/KLF family of transcription factors". Genomics. 87 (4): 474–82. doi:10.1016/j.ygeno.2005.12.011. PMID   16460907.
  17. ↑ Perdomo, J; Holmes, M; Chong, B; Crossley, M (December 2000). "Eos and pegasus, two members of the Ikaros family of proteins with distinct DNA binding activities". Journal of Biological Chemistry. 275 (49): 38347–54. doi: 10.1074/jbc.M005457200 . PMID   10978333.
  18. ↑ Perdomo, J; Holmes, M; Chong, B; Crossley, M (December 2000). "Eos and pegasus, two members of the Ikaros family of proteins with distinct DNA binding activities". Journal of Biological Chemistry. 275 (49): 38347–54. doi: 10.1074/jbc.M005457200 . PMID   10978333.
  19. ↑ Tsang, AP; Visvader, JE; Turner, CA; et al. (July 1997). "FOG, a multitype zinc finger protein, acts as a cofactor for transcription factor GATA-1 in erythroid and megakaryocytic differentiation". Cell. 90 (1): 109–19. doi: 10.1016/s0092-8674(00)80318-9 . PMID   9230307. S2CID   2085524.
  20. ↑ Holmes, M; Turner, J; Fox, A; Chisholm, O; Crossley, M; Chong, B (August 1999). "hFOG-2, a novel zinc finger protein, binds the co-repressor mCtBP2 and modulates GATA-mediated activation". Journal of Biological Chemistry. 274 (33): 23491–890. doi: 10.1074/jbc.274.33.23491 . PMID   10438528.
  21. ↑ Turner, J; Crossley, M (September 1998). "Cloning and characterization of mCtBP2, a co-repressor that associates with basic Krüppel-like factor and other mammalian transcriptional regulators". EMBO Journal. 17 (17): 5129–40. doi:10.1093/emboj/17.17.5129. PMC   1170841 . PMID   9724649.
  22. ↑ "theconversation.com/profiles/merlin-crossley-22601/articles". theconversation.com. 15 December 2021.
  23. ↑ "The Bragg UNSW Press Prize for Science Writing". newsouthpublishing.com.
  24. ↑ "Board members - AusSMC - Australian Science Media Centre". www.smc.org.au.
  25. ↑ "Australian Museum Trustees". australianmuseum.net.au.
  26. ↑ "SIMS is a collaboration which is stronger than its individual parts/articles". sims.org.au.
  27. ↑ https://www.gg.gov.au/kings-birthday-2023-honours-list . Retrieved 12 June 2023.{{cite web}}: Missing or empty |title= (help)
  28. ↑ "Winner of 2023 FAOBMB Award for Research Excellence" . Retrieved 12 March 2023.
  29. ↑ "HE 2021 LEMBERG MEDAL: MERLIN CROSSLEY" . Retrieved 7 August 2021.
  30. ↑ "2020 Category Winners". 27 October 2020. Retrieved 7 August 2021.
  31. ↑ "Fellows - The Royal Society of NSW". royalsoc.org.au.
  32. ↑ College, Queen's (22 November 2017). "Fellows - Queen's College - The University of Melbourne - Queen's College - The University of Melbourne". www.queens.unimelb.edu.au.
  33. ↑ http://www.lornegenome.asnevents.com.au/index84bb.html?option=com_content&view=article&id=38&Itemid=29%5B%5D
  34. ↑ "Australian Academy of Science - Gottschalk medal". Archived from the original on 26 August 2014. Retrieved 11 December 2014.
  35. ↑ "Edgeworth David Medal". Archived from the original on 20 July 2014. Retrieved 26 August 2014.
  36. ↑ "Medalists". asbmb.org.au.
  37. ↑ "Rhodes Scholars: Complete List, 1903-2013". Archived from the original on 6 November 2013. Retrieved 7 August 2021.
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