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  Evaluating Photodynamic Therapy in colorectal cancer using patient-derived organoids


   Faculty of Life Sciences

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

About the Project

Colorectal cancer (CRC) is the 3rd most common cancer worldwide. Surgery is first line treatment and often in adjunct with chemotherapy. However, up to 20% of patients develop recurrent disease after treatment. Photodynamic Therapy (PDT) is an emerging anti-cancer treatment method, which can substantially improve the outcomes of treatment in CRC. PDT involves the administration of a photosensitising agent to cancers, followed by the irradiation of light to the cancer growth. This results in the activation of the photosensitising agent, eliciting cell death through the generation of reactive oxygen species and oxidative stress. This project will involve the investigation of PDT in CRC using different in vitro models of CRC. Recently, it has been identified that 2D cell cultures are not adequate and efficient in providing reliable and clinically representative outcomes of treatment. This is due to the limited capacity and application of 2D cell cultures and their lack of representation of clinical cancers. 3D spheroidal cell cultures and more recently, patient-derived organoids have been identified as vastly more improved and better models of CRC to pre-clinically evaluate treatments.

In this project, PDT will be evaluated in simple 2D monolayer and more advanced 3D spheroidal cell monocultures and co-cultures of CRC. In our laboratory, we culture patient-derived organoids, directly from CRC patients in Leeds and will be used in this PhD project to study PDT treatments. The candidate will liaise with the colorectal surgery team at St James Hospital to collect and process CRC tissue specimens from theatre into organoids. Organoids will be subjected to PDT and other cancer treatments and interrogated on a molecular level to identify novel markers of chemoresistance.

Methods: Cell line and tissue culturing, patient-derived organoid culturing, cell viability assays, fluorescent microscopy, immunofluorescence, immunohistochemistry, western blotting, RT-PCR, single cell analyses, statistical analyses

How to apply

Formal applications can be submitted via the University of Bradford web site; applicants will need to register an account and select 'Full-time PhD in Biomedical Science' as the course, and then specify the project title when prompted.

About the University of Bradford

Bradford is a research-active University supporting the highest-quality research. We excel in applying our research to benefit our stakeholders by working with employers and organisations world-wide across the private, public, voluntary and community sectors and actively encourage and support our postgraduate researchers to engage in research and business development activities.

Positive Action Statement

At the University of Bradford our vision is a world of inclusion and equality of opportunity, where people want to, and can, make a difference. We place equality and diversity, inclusion, and a commitment to social mobility at the centre of our mission and ethos. In working to make a difference we are committed to addressing systemic inequality and disadvantages experienced by Black, Asian and Minority Ethnic staff and students.

Under sections 158-159 of the Equality Act 2010, positive action can be taken where protected group members are under-represented. At Bradford, our data show that people from Black, Asian, and Minority Ethnic groups who are UK nationals are significantly under-represented at the postgraduate researcher level. 

These are lawful measures designed to address systemic and structural issues which result in the under-representation of Black, Asian, and Minority Ethnic students in PGR studies.

Biological Sciences (4) Medicine (26)

Funding Notes

This is a self-funded PhD project; applicants will be expected to pay their own fees or have a suitable source of third-party funding. A bench fee may apply in addition to tuition fees. UK students may be able to apply for a Doctoral Loan from Student Finance for financial support.

References

Kim, W.S., Khot, M.I., Woo, H.M., Hong, S., Baek, D.H., Maisey, T., Daniels, B., Coletta, P.L., Yoon, B.J., Jayne, D.G. and Park, S.I., 2022. AI-enabled, implantable, multichannel wireless telemetry for photodynamic therapy. Nature communications, 13(1), pp.1-11.
Khot, M.I., Perry, S.L., Maisey, T., Armstrong, G., Andrew, H., Hughes, T.A., Kapur, N. and Jayne, D.G., 2018. Inhibiting ABCG2 could potentially enhance the efficacy of hypericin-mediated photodynamic therapy in spheroidal cell models of colorectal cancer. Photodiagnosis and photodynamic therapy, 23, pp.221-229.
Kondo, J., Endo, H., Okuyama, H., Ishikawa, O., Iishi, H., Tsujii, M., Ohue, M. and Inoue, M., 2011. Retaining cell–cell contact enables preparation and culture of spheroids composed of pure primary cancer cells from colorectal cancer. Proceedings of the National Academy of Sciences, 108(15), pp.6235-6240.

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