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Investigating anti-cancer drug delivery mechanisms to mucinous colorectal cancers


   Faculty of Biology, Medicine and Health

  ,  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

Mucinous adenocarcinomas are a type of tumour found in many organs but most commonly presenting in colorectal or breast cancer patients. They are defined by their excessive secretion of enormous, tumour-cell derived, glycoproteins that gel together to form mucus. The energetic burden of mucus production on the tumour cells leads to the hypothesis that there is an advantage for these cells to produce them in such large quantities. Perhaps related to this are the clinical observations that patients with mucinous tumours have a poorer chance of survival and a worse response to chemotherapy. Exactly how mucus production impacts cancer cell biology and patient outcomes is poorly understood. This presents the need to discover more about mucinous tumours, their cellular activities, and abilities to resist therapies.

This project will build new cell models and molecular methods to allow us to explore the effect of mucus on cancer cells and cancer drug delivery. Focusing on colorectal cancer as the most common site of mucinous cancers you will work with tumour organoids, purified mucus from patients and current chemotherapy agents to ask these important questions.

- How does transformation alter cells in mucinous tumours to allow for vast secretion of mucus?

- What benefit do tumour cells gain from secreting mucus?

- Can mucus protect tumour cells from anti-cancer therapies, reducing their effectiveness?

- Can targeting the pathways important for the production of mucus improve therapy?

The project will be performed in the Oglesby Cancer Research Building, a custom-built, well-equipped, and modern cancer research facility situated on the same site as the Christie Hospital and the CRUK Manchester Institute. The opportunity to study in this environment will provide the resources and interactions needed for this project to succeed.

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 View Website

References


Knight J, Alexandrou C, Skalka G, Vlahov N, Pennel K, Officer L, Teodosio A, Kanellos G, Gay D, May-Wilson S, Smith E, Najumudeen A, Gilroy K, Ridgway R, Flanagan D, Smith R, McDonald L, MacKay C, Cheasty A, McArthur K, Stanway E, Leach J, Jackstadt R, Waldron J, Campbell A, Vlachogiannis G, Valeri N, Haigis K, Sonenberg N, Proud C, Jones N, Swarbrick M, McKinnon H, Faller W, Le Quesne J, Edwards J, Willis A, Bushell M and Sansom O (2021). MNK inhibition sensitizes KRAS-mutant colorectal cancer to mTORC1 inhibition by reducing eIF4E phosphorylation and c-MYC expression. Cancer Discovery. (doi:10.1158/2159-8290.CD-20-0652).
Knight J, Vlahov N, Gay D, Ridgway R, Faller W, Proud C, Mallucci G, von der Haar T, Smales M, Willis A and Sansom O (2021). Rpl24Bst mutation suppresses colorectal cancer by promoting eEF2 phosphorylation via eEF2K. Elife. (doi.org/10.7554/eLife.69729).
McShane A, Bath J, Jaramillo A, Ridley C, Walsh A, Evans C, Thornton D.J and Ribbeck K (2021). Mucus. Current Biology. (doi.org/10.1016/j.cub.2021.06.093).
Kishimoto H, Ridley C, and Thornton D.J. (2022). The lipophilic cyclic peptide cyclosporin A induces aggregation of gel‑forming mucins. (doi.org/10.1038/s41598-022-10125-y)
Benesch M and Mathieson A (2020). Epidemiology of Mucinous Adenocarcinomas. Cancers. (doi:10.3390/cancers12113193).

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