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Omics approaches to reveal novel players regulating cell signalling in breast cancer


   Faculty of Biology, Medicine and Health

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  Dr C Francavilla, Dr J-M Schwartz, Prof Robert Clarke  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

There is an unmet need for novel molecular targeted therapies to improve breast cancer patient survival outcomes. Available therapies for breast cancer patients are based on surgery, radiation, or targeted therapies mostly directed against signalling players, like kinases. However, targeting a single signalling molecule has been often proven insufficient for long-term disease control, for instance due the lack of a full understanding of signalling rewiring in response to changes in the breast cancer microenvironment (e.g. stress signals).

In such an environment, Receptor Tyrosine Kinases (RTKs) expressed on epithelial cells respond to their ligands by activating intracellular signalling cascades and regulating proliferation. The ability of cells to integrate growth and stress signals is compromised in breast cancer but we still do not know the molecular mechanisms underlying this. By elucidating signalling changes under stress conditions, this proposal aims at uncovering novel combinations of signalling nodes amenable for therapeutic intervention in patients.

Such novel molecular targets may replace or complement existing systemic treatment strategies. We will test this hypothesis by combining omics experiments, bioinformatics, and functional assays in breast cancer models, including cell lines and patient-derived sample.

Entry Requirements

Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in a related area/subject. Candidates with previous laboratory experience are particularly encouraged to apply.

How To Apply

For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries may be made directly to the primary supervisor. On the online application form select the appropriate subject title.

For international students, we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences.

Equality, Diversity and Inclusion

Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website https://www.bmh.manchester.ac.uk/study/research/apply/equality-diversity-inclusion/”


Funding Notes

Applications are invited from self-funded students. This project has a Band 3 fee. Details of our different fee bands can be found on our website https://www.bmh.manchester.ac.uk/study/research/fees/

References

1. Watson J., Schwartz J-M., Francavilla C.*, Using Multilayer Heterogeneous Networks to Infer Functions of Phosphorylated Sites. (2021). J Proteome Res. 2021 Jul 2;20(7):3532-3548. doi: 10.1021/acs.jproteome.1c00150
2. Smith M.P., Ferguson H.R., Ferguson J., Zindy E., Kowalczyk K.M., Kedward T., Bates C., Parsons J., Watson J., Chandler S., Fullwood P., Warwood S., Knight D., Clarke R.B., Francavilla C.*. Reciprocal Priming between RTKs at Recycling Endosomes Orchestrates Cellular Signalling Outputs. (2021). The EMBO Journal. Jun 4:e107182. doi: 10.15252/embj.2020107182.
3. Yap C. F., Garcia-Albornoz M., Jarnuczak A.F., Hubbard S. J., Schwartz J-M*. Model parameterization with quantitative proteomics: case study with trehalose metabolism in Saccharomyces cerevisiae. (2021.) Processes 9: 139
4. Woo et al., PDXNET consortium & EurOPDX consortium (Clarke RB) (2021) Conservation of copy number profiles during engraftment and passaging of patient-derived cancer xenografts. Nature Genetics, 53(1):86-99.
5. Simões BM, Santiago-Gómez A, Chiodo C, Moreira T, Conole D, Lovell S, Alferez D, Eyre R, Spence K, Sarmiento-Castro A, Kohler B, Morisset L, Lanzino M, Andò S, Marangoni E, Sims AH, Tate E, Howell SJ and Clarke RB (2020) Targeting STAT3 signalling using stabilised sulforaphane (SFX-01) inhibits endocrine resistant stem-like cells in ER-positive breast cancer. Oncogene, 39(25):4896-4908.
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