About the Blog and the Lab:
This blog aims to answer the question: What’s Lab Life Like? Hopefully, together with other social media activities, it will help strengthen the global community of people, be they scientists or others, who care about research.
We are a conventional molecular and cell biology lab at UNSW Sydney. We study gene regulation and how DNA-binding proteins, termed transcription factors, turn genes on and off. Our hope is that our work will contribute to new therapeutic strategies for blood diseases and metabolic disorders. We have recently been working with CRISPR-mediated gene editing with a view to treating Sickle Cell Anaemia (see below for more information about our work).
Merlin Crossley enjoys research, teaching and even university administration.
His training included a BSc (Hons) at the University of Melbourne, and a doctorate at Oxford University investigating the molecular genetics of haemophilia B. He then moved to a post-doctoral position at Harvard Medical School where he investigated gene control in blood cells. He returned to Australia and took up a lectureship at the University of Sydney. In 2006 he was awarded a Vice-Chancellor’s Award for Excellence in Higher Degree Student Supervision. He moved to UNSW as Dean of Science at the end of 2009. In February 2016, he was appointed to the role of Deputy Vice-Chancellor (Education) then in 2017 Deputy Vice-Chancellor (Academic).
About our research:
- Haemophilia B Leyden: More than fifty years ago a form of the inherited bleeding disorder, haemophilia, was described that was highly unusual in that patients recovered after puberty. Crossley showed how the disease was caused by mutations that affected the expression of the clotting factor IX gene and that the patients (all boys, given this is an X-linked disorder) recovered as a result of a Testosterone Responsive Element which drove expression of the gene as testosterone levels rose. This work was published in Nature, Science, the American Journal of Human Genetics, and Trends in Genetics.
- Thalassaemia and Sickle Cell Anaemia: Mutations in the genes that encode haemoglobin – the oxygen carrying entity found in red blood cells – cause serious, lifelong, inherited diseases. One approach to alleviating symptoms is to re-activate a related gene – the foetal globin gene – that is active early in development in utero. Several naturally occurring mutations cause this gene to be highly expressed throughout life. Our work showed that the mutations disrupt the binding sites for two powerful gene repressors – BCL11A and ZBTB7A/LRF. Mimicking these mutations, using CRISPR gene editing to introduce the mutations into blood stem cells, is seen as a possible cure for these disorders. This work has been published in Science, Nature Genetics, Nature Communications, and Blood.
- Identification, cloning and characterisation of genes encoding gene regulatory DNA-binding proteins and their co-factors: Specific genes are turned on and off by DNA-binding proteins that recognise short sequence motifs in their target genes and localise to these genes (usually just upstream in the DNA), These proteins then recruit various active complexes (often containing enzymes) that alter gene expression, typically either by directly recruiting the machinery that will transcribe the gene into RNA, or affecting the packaging of DNA to make the gene more or less accessible to this machinery. Over the last twenty years there has been an intense focus on identifying and isolating the genes that encode these DNA-binding proteins and their co-factors. The laboratory and I have led or contributed to the cloning of genes for several important DNA-binding proteins, including KLF3, KLF8, KLF17, Pegasus and Eos, and co-factors, including FOG1, FOG2 and CtBP2. This work was published in journals, including Cell, The EMBO Journal., Nucleic Acids Research, Molecular and Cellular Biology, and the Journal of Biological Chemistry.