Bioinformatics Seminars

Bioinformatics Seminar

Time:
Venue: Na

3 December 2019

Na

Using systems-level computational approaches to reveal mechanisms of cancer plasticity

Holly Whitfield
WEHI Bioinformatics

Malignant tumours are well adapted to excessive proliferation and survival ; characteristics that are shaped by an evolutionary process. Tumours are produced through the proliferation of tumorigenic subpopulations ; dependent upon selective pressures ; intercellular signaling ; and the plasticity of cellular phenotype. To understand the regulatory processes that govern this plasticity ; we must reconstruct the molecular mechanisms though which individual cells respond to their tumour microenvironment and how these orchestrate phenotypic plasticity.

Cellular plasticity emerges from multiple molecular layers of regulation - genomic ; transcriptomic and proteomic - which are captured by a range of data types and through various experimental models. I will present some preliminary work on a fluorescence barcoded cell line model of breast cancer progression ; where I identified a transcriptomic signal of plastic adaptability to metastatic environments. I then propose a mapping framework to integrate these data with other resources to infer regulatory mechanisms ; leveraging the strengths of these models and the benefits of other large-scale datasets.

The expansion of small-scale datasets enables gene regulatory network reconstruction ; which would otherwise be of insufficient size for modelling and mechanistic reconstruction. The reconstruction of regulatory mechanisms that underpin cellular plasticity within cancer will not only contribute to our understanding of non-genetic tumour heterogeneity and cancer progression ; but may also lead to the development of therapeutics to directly target and reduce plasticity ; modifying cells into a vulnerable or readily eradicated state.;Actual Venue : Davis Auditorium;;;;


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