Winner of 2023 FAOBMB Award for Research Excellence

Professor Merlin Crossley is the winner of the 2023 FAOBMB Award for Research Excellence

Professor Merlin Crossley

School of Biotechnology and Biomolecular Sciences
University of New South Wales, Australia

Merlin Crossley is an expert on human gene regulation and how it relates to inherited blood disorders, such as Hemophilia and Sickle Cell Anemia. Most recently, he has pioneered new CRISPR-gene editing strategies to introduce naturally occurring beneficial mutations into blood stem cells as a form of somatic gene therapy.

Merlin completed a BSc Hons at the University of Melbourne. He undertook his Honours training year in the laboratory of Jim Pittard studying gene regulation in bacteria. He moved to Oxford (United Kingdom) and investigated an unusual form of hemophilia, termed Hemophilia B Leyden that resolves after puberty, undertaking his doctorate with George Brownlee. He showed how point mutations in the promoter disrupted the binding sites for activator proteins, thereby causing hemophilia; his studies revealed that a cryptic binding site for the Androgen Receptor explained the recovery after puberty.

He then went to Harvard (United States) as a postdoctoral fellow to study the developmental regulation of the hemoglobin genes with Stu Orkin. He worked on erythroid transcription factors, such as GATA1, and was involved in cloning new genes encoding transcription factors and their co-factors, such as KLF3 and FOG (ZFPM1). Back in Australia at the University of Sydney his lab identified new members of the Ikaros family (Eos IKZF4 and Pegasus IKZF5), new KLF members (KLF8 and 17) and cofactors CtBP2 and, in collaboration with others, FOG2 (ZFPM2).

In 2010 Merlin moved to the University of New South Wales and started focussing on the mutations associated with Hereditary Persistence of Fetal Hemoglobin. These mutations are of clinical interest as they essentially reactivate and boost the expression of fetal globin, which ameliorates the symptoms of both Sickle Cell Disease and beta-thalassemia. He showed how various mutations in the fetal globin promoters either generated new sites for activators or disrupted repressor binding sites. His lab also showed how deletions of the beta-globin promoter alleviated fetal globin silencing and provided another mechanism for boosting fetal globin expression. These mutations can now be introduced into blood stem cells via CRISPR editing or base editing. This work, therefore, represents a new approach to gene therapy for inherited globin disorders that may supersede gene replacement strategies that rely on insertional mutagenesis via retroviruses and lentiviruses.

In addition to his research contributions, Merlin is an enthusiastic lecturer and science communicator. He is Chair of the Editorial Board of The Conversation, and Chair of the Board of University of New South Wales Press, Deputy Chair of the Australian Science Media Centre, a member of the Editorial Board of BioEssays, and an Honorary Associate of the Australian Museum. He also contributes to university management, having served in the roles of Dean of Science, Deputy Vice-Chancellor Research and Deputy Vice-Chancellor Education. In the last-named role he has recently supported the establishment of a community of Education Focussed staff who can, but are not required to, do research. This has had benefits for both students and staff.

Merlin has been recognized by multiple awards, including a Rhodes Scholarship, the Gottschalk Medal from the Australian Academy of Science (2002), Lorne Genome’s Julian Wells Medal (2010), the NSW Premier’s Award for Medical Biological Science (2020), the Lemberg Medal from the Australian Society for Biochemistry and Molecular Biology (2021). Also in 2021, a new species of iridescent butterfly bobtail squid was named in his honour – Iridoteuthis merlini – Merlin’s bobtail squid.

Photo: Karen Gowlett-Holmes, CSIRO

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