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Network Pharmacology for Novel Cancer Combination Therapies and Diagnostics

PhD project title and outline, including interdisciplinary dimension:
Network Pharmacology for Novel Cancer Combination Therapies and Diagnostics

This interdisciplinary project connects clinical outcomes and biological mechanism in order to advance
cancer therapy, applying data-intensive, systems medicine approaches. Genome-scale biochemical
interaction networks will provide an interaction map for graph-theoretic analysis of existing drug response
datasets. Multiple functional genomics datasets from drug-treated cells provide signatures of drug
response and hence insight into drug mode of action. Transcriptome and rich clinical data from prostate
cancer patients will provide for investigation of candidate biomarkers and response modules identified in
analysis of the cell line data. Key areas of research are:

1. Modelling gene function in cancer drug resistance and response; towards systems-wide executable
models.
2. Identification of candidate drug combinations to drive tumour cell networks towards therapeutic endpoints
(e.g. apoptosis). Prostate cancer will be an exemplar, where significant in vitro and clinical data
are available in collaboration with the Mills group and the Belfast-Manchester Movember National
Centre of Excellence.
3. Development of novel algorithms, techniques and computational workflows; including tools to risk
stratify patients by survival and response to treatment . For example, one strand will work towards
developing a companion diagnostic linked to candidate combination therapy from computational
analysis.
4. Training will be provided in a range of research competencies across multiple disciplines including:
cancer biology, polyomics data integration, cluster computing, biomedical statistics, computer
programming, network biology, genetics, systems pharmacology, precision medicine. Training will also
include transferable skills for example in: scientific method, critical thinking, problem-solving,
communicating results etc.. There will be opportunity for wet-laboratory work with prostate cancer cell
lines and organoids (Mills), following up computational results.
5. This project involves collaboration with GlaxoSmithKline who will provide datasets and computational
workflows; interactions will include regular visits and a six-month placement during the second year of the studentship.

Primary supervisor: Dr Ian Overton (Medicine, Dentistry and Biomedical Science)
Secondary supervisor: Dr Ian Mills (Medicine, Dentistry and Biomedical Science)
External Partner/Organisation: GSK