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Dr Damien Hudson
Dr Damien Hudson is joint head of Chromosome Research at Murdoch Childrens Research Institute. His group focuses on the fundamental question of how a cell compacts its DNA nearly 10,000 fold and then faithfully segregates its replicated genome into two daughter cells, as it pertains to many aspects of human health ( i.e., cancer, aging, birth defects and development).
Dr Hudson’s group studies a master regulator of chromosome folding, termed the condensin complex. The group was the first to identify vertebrate binding sites of condensin in vertebrates and found that the complex associated predominately with gene regulatory regions. The discovery has led to a new area of research into a complex that previously has been studied almost primarily in relation to mitosis, but now appears fundamental to gene regulation. The new link between condensin and gene regulation, in addition to its well characterized role in chromosome segregation, are providing vital clues why condensin mutations are increasingly associated with developmental disorders and most notably cancers.
Dr Hudson received his PhD through the University of Melbourne in 1999. He then did postdoctoral studies at the Wellcome Centre for Cell Biology in Edinburgh, United Kingdom where he was awarded the prestigious Caledonian Fellowship from the Royal Society of Edinburgh. In late 2007 he returned to Australia at the Murdoch Childrens Research Institute where he started his own group.
Caledonian Fellowship, The Royal Society of Edinburgh, 2003
How a cell compacts its DNA and then faithfully segregates its replicated genome into two daughter cells is still a major unanswered question in biology. The correct packing of DNA is essential to chromosome segregation during mitosis and gene regulation in interphase. Chromosome loss and gene deregulation are leading cause of diseases and cancers.
Dr Damien Hudson studies factors that are involved in the organisation and structure of chromosomes. His team is focusing on a master regulator of chromosome compaction known as the condensin complex. Condensin is a core component of chromosomes, and is present in every species from bacteria to human. Akin to histones, condensin modifies and marks DNA, and has pivotal roles in chromosome condensation, DNA repair, and gene regulation and is touted as a global organiser of the genome due to its many functions.
The team’s achievements extend from generating and characterising the first conditional knockout of a condensin subunit and finding a key role of the complex in the formation of the chromosome scaffold, to using next generation sequencing to deciphering the first genome wide map of condensin in vertebrates and revealing condensin binds gene regulatory regions. This is a new and exciting field, and an area that is of central importance in disease.
They are using proteomics approaches to define the condensin interactome and also the structure of the complex, conditional knockouts and live cell imaging to elucidate the function and next generation sequencing to understand where condensin binds in the genome and how this influences gene expression.
- Understanding how condensin controls gene regulation
- Creating mouse knockout and knockin models of condensin
- Using genome editing to understand how condensin mutations are linked cancer
- Creating conditional knockouts in cell lines of chromosomal proteins
Bakhrebah M, Zhang T, Mann JR, Kalitsis P, Hudson DF. (2015) Disruption of a conserved CAP-D3 threonine alters condensin loading on mitotic chromosomes leading to chromosome hyper-condensation. J Biol Chem. 290: 6156-67
Barysz H, Kim JH, Chen ZA, Hudson DF, Rappsilber J, Gerloff DT, Earnshaw WC. (2015). 3D topology of the SMC2/SMC4 sub-complex from chicken chicken I revealed by cross-linking and molecular modelling. Open Biology. 5(2) doi: 10.1098/rsob.150005.
Kim JH, Zhang T, Wong N, Davidson N, Maksimovic J, Oshlack A, Earnshaw WC, Kalitsis P Hudson DF. (2013) Condensin I associates with structural and gene regulatory regions in vertebrate chromosomes. Nat Commun 2013 4: 2537. doi: 10.1038/ncomms3537.
Green LC, Kalitsis P, Chang TM, Cipetic M, Kim JH, Marshall O, Turnbull L, Whitchurch CB, Vagnarelli P, Samejima K, Earnshaw WC, Choo KH, Hudson DF. (2012) Contrasting roles of condensin I and II in mitotic chromosome formation. J Cell Sci 125:1591-1604.
Ohta S, Bukowski-Wills JC, Sanchez-Pulido L, Alves Fde L, Wood L, Chen ZA, Platani M, Fischer L, Hudson DF, Ponting CP, Fukagawa T, Earnshaw WC, Rappsilber J (2010). The protein composition of mitotic chromosomes determined using multiclassifier combinatorial proteomics. Cell 142: 810-821
Kim JH, Chang TM, Graham AN, Choo KH, Kalitsis P, Hudson DF. (2010) Streptavidin-Binding Peptide (SBP)-tagged SMC2 allows single-step affinity fluorescence, blotting or purification of the condensin complex. BMC Biochem 11: 50.
Hudson DF, Marshall KM, Earnshaw WC. (2009) Condensin-Architect of mitotic chromosomes. Chrom Res 17: 131-144
Hudson DF, Ohta S, Freisingner T, MacIsaac F, Sennel L, Alves F, Kerr A, Rappsilber J, Earnshaw WC. (2008) Molecular and genetic analysis of condensin function in vertebrate cells. Mol Biol Cell 19: 3070-3079
Vagnarelli P, Hudson DF, Ribeiro SA, Trinkle-Mulcahy L, Spence JM, Farr CJ, Lamond AI, Earnshaw WC. (2006) Condensin and Repo-Man/PP1 co-operate in the regulation of chromosome architecture during mitosis. Nat Cell Biol 8: 1133-1142
Hudson DF, Vagnarelli P, Gassmann R, Earnshaw WC. (2003) Condensin is required for nonhistone protein assembly and structural integrity of vertebrate mitotic chromosomes. Dev Cell 5: 323-336
- National Health and Medical Research Council