SIP Series - Nicole Bryce
Topic: Unbiased chemical screening of the actin cytoskeleton – an image based approach
Actin regulators constitute a largely unexploited pool of prospective drug targets that could facilitate precise and selective actin modulation. Screening of 114,400 structurally diverse compounds using high-content F-actin imaging with unbiased phenotypic clustering identified just 27 recurrent actin phenotypes. This implies surprisingly low plasticity given the combinatorial potential of actin regulators and the scope of chemical perturbations applied.
More than 2600 compounds impacted actin organisation and we employed 3 strategies based on phenotypic comparison to enhance prediction of underlying mechanisms: 1) comparison with known actin modulators embedded in the screen (>260 compounds identified); 2) comparison with known genetic perturbations (3 novel talin-binding compounds), and; 3) retrospective integration of additional controls into the original screen data (2 ROCK inhibitors). The retrospective integration strategy may provide near-unlimited capacity to extend mechanistic analyses in this and other phenotypic screens.
About the speaker
Nicole Bryce, University of New South Wales
Nicole completed her PhD in 2003 through the University of Sydney, in the laboratory of Prof. Peter Gunning at the Children’s Hospital at Westmead. During her PhD, Nicole discovered that individual tropomyosin isoforms had distinct cellular functions. Nicole completed a postdoctoral fellowship at Vanderbilt University Medical Center, Nashville, where she worked on the roles of lamellipodial actin proteins in both 2D and 3D cancer cell migration in the laboratory of Prof. Alissa Weaver. Upon returning to Australia in 2008, she has worked in Prof. Trevor Hambley’s laboratory developing 3-dimensional cellular models of drug diffusion, Assoc. Prof Brain Hawkett’s laboratory on nanoparticle penetration and drug delivery into 3D tumour models and Assoc. Prof Guy Lyon’s laboratory on clonal co-operation in cancer. Currently based in Prof. Peter Gunning and Prof. Edna Hardeman’s laboratory at UNSW, Nicole works on both the basic science of tropomyosin isoforms as well as a large-scale drug discovery project to discover new anti-tropomyosin compounds.