Cancer: Epigenetic therapy using microbubble-mediated drug delivery for colorectal cancer

The project is an interdisciplinary, pre-clinical study that aims to investigate the response of human tumour cells to treatment with epigenetic inhibitors (including DNA methyltransferase inhibitors, HDAC inhibitors and/or vitamin C), as a potential combination therapy for colorectal cancer (CRC). As epigenetic modifications contribute to tumour growth, drugs that modify the epigenome have great potential for cancer therapy. Epigenetic drugs have the capability to target cancer stem cells, restore sensitivity of tumour cells to chemotherapy or to prime tumours prior to secondary treatment with immune checkpoint inhibitors.

<p>Tumour cell lines will be tested for response to combination drug treatments using 2D/3D cell culture and other models. Microbubbles will be generated using the University of Leeds patented microfluidic system, and could be combined with liposomes containing encapsulated drugs. Novel cancer models or therapeutic microbubbles could be developed further for targeted drug delivery. Our long-term aim is for microbubble delivery to deliver drugs more efficiently to tumours, to enhance therapeutic response and to minimize off-target side effects.</p> <p>Reference: Ingram N. <em>et al</em>. Ultrasound-triggered therapeutic microbubbles enhance the efficacy of cytotoxic drugs by increasing circulation and tumour drug accumulation and limiting bioavailability and toxicity in normal tissues. Theranostics 2020; 10(24): 10973&ndash;10992.</p> <p>You will work closely with members of other groups at the University of Leeds including Professor&nbsp;Evans&rsquo; group in the School of Physics and Astronomy. The project will involve training in a wide variety of techniques and research skills. These may include mammalian cell culture, drug testing using monolayer or spheroid/organoid cell culture, molecular biology and cell biology techniques to monitor epigenetic biomarkers of response, generation and testing of functional microbubbles in cancer models and drug delivery.</p> <p>You will be trained as part of an established, interdisciplinary team of clinicians, academics and research scientists-&nbsp;<a href="http://www.microbubbles.leeds.ac.uk/">the Leeds Microbubble Consortium</a>- that includes PhD researchers from other Schools in the University.</p> <p>This project is part of the <a href="https://medicinehealth.leeds.ac.uk/leeds-institute-research-st-james/doc/international-phd-academy-medical-research">International PhD Academy: Medical Research</a>.</p> <p><strong>In line with the bespoke nature of our International PhD Academy a modified PhD project can be proposed dependent on students interests and background.</strong></p>

<p>Please note these are not standalone projects and applicants must apply to the PhD academy directly.</p> <p>Applications can be made at any time. You should complete an <a href="https://medicinehealth.leeds.ac.uk/faculty-graduate-school/doc/apply-2">online application form</a> and attach the following documentation to support your application.&nbsp;</p> <ul> <li>a full academic CV</li> <li>degree certificate and transcripts of marks (or marks so far if still studying)</li> <li>Evidence that you meet the programme&rsquo;s minimum English language requirements (if applicable, see requirement below)</li> <li>Evidence of funding to support your studies</li> </ul> <p>To help us identify that you are applying for this project please ensure you provide the following information on your application form;</p> <ul> <li>Select PhD in Medical Research as your programme of study</li> <li>Give the full project title and name the supervisors listed in this advert</li> </ul>

A degree in biological sciences, dentistry, medicine, midwifery, nursing, psychology or a good honours degree in a subject relevant to the research topic. For entry requirements for all other research degrees we offer, please contact us.

Applicants whose first language is not English must provide evidence that their English language is sufficient to meet the specific demands of their study. The minimum requirements for this programme in IELTS and TOEFL tests are: &bull; British Council IELTS - score of 7.0 overall, with no element less than 6.5 &bull; TOEFL iBT - overall score of 100 with the listening and reading element no less than 22, writing element no less than 23 and the speaking element no less than 24.

<p>Informal enquires about regarding the bespoke taught first year of the PhD programme and research projects can be made by contacting <a href="mailto:LIMRPhD@leeds.ac.uk">LIMRPhD@leeds.ac.uk</a>.</p> <p>Enquiries regarding the application process should be directed to the Faculty of Medicine and Health Graduate School e: <a href="mailto:fmhpgradmissions@leeds.ac.uk">fmhpgradmissions@leeds.ac.uk</a></p>