VHTO - Landelijk expertisebureau meisjes/vrouwen en bčta/techniek


 




Austin, Caroline

Caroline grew up on a dairy farm in Cornwall, in this rural community it was usual for girls as well as boys to help on the farm including tractor driving from a young age. Role models whilst growing up included the crew of the Star Ship Enterprise and her teachers at school. She moved to London to do a Biochemistry BSc and then a PhD. She carried out post-doctoral research at the University of London and at Harvard University, before she joined the Faculty at  Newcastle University in 1993. First as a Lecturer in Biochemistry and Genetics, then as a Senior Lecturer, then as a Professor from 2005. She has run a research group at Newcastle University since 1993. She has supervised more than 20 PhD students and been a mentor to many early career scientists. She has been a member of the MRC non clinical career development panel, and reviews grants and scientific papers. She supports the Athena SWAN charter and has sat on Athena SWAN panels at the Equality Challenge Unit, London.

 

Caroline is an international expert on DNA topoisomerases. Type II DNA topoisomerases are essential, they catalyse topological rearrangements within DNA. Vertebrates have two isoforms, TOP2A and TOP2B. Caroline Austin co discovered TOP2B nearly 30 years ago. She cloned and expressed human TOP2B for biochemical studies including site directed mutagenesis of evolutionarily conserved amino acid residues. Using random mutagenesis and a heterologous yeast expression system catalytically functional drug resistance mutations were isolated, interestingly three of these (H514Y; G550R; A596T) are immediately adjacent to lysine’s that get ubiquitinated. Caroline was also involved in the crystallisation of the core of human TOP2A. Her group developed the trapped in agarose DNA immunostaining (TARDIS) assay to analyse covalent topoisomerase II DNA complexes within cells. This has been used to determine the molecular pharmacology of drugs that target TOP2A and TOP2B. Type II topoisomerases are an important anticancer drug target, being targeted by etoposide, mitoxantrone and anthracyclines such as doxorubicin and epirubicin. These drugs can cause therapy related leukaemia, and the Austin lab demonstrated that TOP2B is implicated in the generation of DNA strand breaks that lead to translocations in the MLL locus and the RUNX1 locus that can cause therapy-related leukaemia. TOP2B is involved in transcriptional regulation. The Austin lab have shown that TOP2B gets redistributed from heterochromatin to euchromatin when histone deacetylase is inhibited and have published a chip seq analysis of TOP2B occupancy across the whole genome following exposure of MCF7 cells to estradiol.  Based on her expertise she has extensive worldwide collaborations with many joint publications with scientists from USA, Canada, France, Spain, Italy, Japan, Australia and Israel. She regularly attends scientific meetings and has co-organised EMBO workshops on DNA topoisomerases.

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