THE 2021 LEMBERG MEDAL: MERLIN CROSSLEY
Deputy Vice-Chancellor Academic
Merlin Crossley became interested in gene regulation as an undergraduate in Jim Pittard’s lab at the University of Melbourne. He moved to Oxford for his doctorate, supported by a Rhodes Scholarship, and investigated the regulation of the clotting factor IX gene in George Brownlee’s lab. He worked on some unusual cases of haemophilia that resolved after puberty, producing papers in Nature and Science. The mutations were among the first ever human regulatory mutations, and the studies showed how single point mutations could dramatically alter developmental gene expression.
Crossley moved to Stu Orkin’s lab in Harvard and investigated the developmental regulation of the globin genes. He identified a new transcription factor Kruppel-like Factor 3 (KLF3), and contributed to the cloning of the essential GATA-1 co-regulator Friend of GATA (FOG/ZFPM1). On returning to a lectureship at the University of Sydney, he worked on identifying several new gene regulatory proteins including co-regulators CtBP2 and FOG2, and new zinc finger transcription factors, EOS (IKZF4), PEGASUS (IKZF5), KLF8 and KLF17. He also began a long running collaboration with Joel Mackay and Jacqui Matthews, resulting in the determination of the structure of several zinc finger complexes.
In 2010, he became Dean of Science at the University of New South Wales (UNSW) and focussed on natural mutations that derepressed the expression of foetal globin and cause hereditary persistence of foetal haemoglobin (HPFH). This condition is beneficial when coinherited with sickle cell disease or thalassemia. His recent work, published in Science, Nature Genetics, Nature Communications, Blood and Trends in Genetics, demonstrated that the HPFH mutations either disrupted binding sites for repressors or generated de novo binding sites for activators. These studies suggested a new gene therapy strategy that involves introducing the mutations via CRISPR gene editing to boost foetal globin production to alleviate sickle cell anaemia or thalassemia, rather than adding a replacement gene.
In 2016, Crossley began leading teaching at UNSW as Deputy Vice-Chancellor Academic. He continues to teach while maintaining his research. Throughout his career he has been recognised for the quality of this research with prizes, including the Edward Chapman Award (Magdalen College, Oxford), Gottschalk Medal (Australian Academy of Science), Julian Wells Medal (Lorne Genome), Edgeworth David Medal (Royal Society of NSW), Roche Medal (ASBMB) and in 2020, the NSW Premier’s Prize for Medical Biological Sciences. He also supports science and science communication as Chair of the Editorial Board of The Conversation, Director of the UNSW Press Board, Deputy Director of the Australian Science Media Centre and as a member of the Australian Museum Council of Governors. He has also held roles on the ASBMB Council and currently uses social media, blogging and twitter, to engage with and help build the community of scientists.