I research DNA repair enzymes involved in cancer and rare genetic diseases, using the tools of biochemistry and structural biology. My goal is to uncover the fine details of DNA damage repair, down to the resolution of individual amino acids. This knowledge will uncover how genetic mutations in individual people increases their risk of disease and will help us design new cancer treatments.
My specific areas of research are:
- to determine how the FANCM protein repairs damage to DNA – damage that if unrepaired can lead to cancer. Mutations in FANCM lead to an increased risk of breast cancer. Our ambitious goal is to determine the structure of the FANCM protein. This will provide us with an improved understanding of FANCM’s role in DNA repair and will allow for more accurate testing and prediction of inherited cancer risk.
- Identifying drug targets in ALT+ cancers and developing molecules which hit existing targets. The ALT+ pathway is active in roughly 10% of cancers and my collaborators have identified a target site in these cells that when disrupted, specifically kills ALT+ cells. I am working on developing the molecules which target this site into a drug suitable for patients, as well as investigating additional potential targets.
My research interests: DNA damage repair and chromatin remodelling, protein structure
Key achievements
2022. SVI Rising Star Award
2021 Victorian Comprehensive Cancer Centre Leadership Scholarship
2020-2023 NHMRC Ideas Grant
2019-2022 National Breast Cancer Foundation Investigator Initiated Research Scheme Grant
2018-2020 SVI Rising Star Fellowship
2014 Institute of Cancer Research, Mel Greaves Science Writing Prize
2013 University of Western Australia, PhD Completion Scholarship
2010 Australian Postgraduate Award Scholarship
Selected publications
MF Sharp, R Bythell-Douglas, AJ Deans, W Crismani. (2021). The Fanconi Anemia ubiquitin E3 ligase complex as an anti-cancer target. Molecular Cell. 81(11):2278-2289.
R Bythell-Douglas, AJ Deans. (2021). A structural guide to the Bloom syndrome complex. Structure. 29(2):99-113.
RJ Aramayo, O Willhoft, R Ayala, R Bythell-Douglas, DB Wigley, X Zhang. (2018). Cryo-EM structures of the human INO80 chromatin-remodeling complex. Nature structural & molecular biology 25 (1), 37.
O Willhöft*, R Bythell-Douglas*, EA McCormack, DB Wigley. (2016). Synergy and antagonism in regulation of recombinant human INO80 chromatin remodeling complex. Nucleic Acids Res. 44(17):8179-88. *Equal contributing authors.
CE Conn, R Bythell-Douglas, D Neumann, S Yoshida, B Whittington, JH Westwood, K Shirasu, CS Bond, KA Dyer, DC Nelson. (2015). Convergent evolution of strigolactone perception enabled host detection in parasitic plants. Science. 349(6247):540-3.
R Bythell-Douglas, U Suttisansanee, GR Flematti, M Challenor, et al. (2015). The crystal structure of a homodimeric Pseudomonas glyoxalase I enzyme reveals asymmetric metallation commensurate with half-of-sites-activity. Chem – Eur J. 21(2):541-4.
ORCID profile: 0000-0002-3823-8749
Google Scholar profile: https://scholar.google.com/citations?user=dsEiDtYAAAAJ&hl=en&oi=ao