约克大学MRC DiMeN Doctoral Training Partnership: Enhancing LNP-RNA delivery to leukemia cells through cutting-edge cryogenic electron tomography (cryo-ET)申请条件要求-申请方
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约克大学
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About the Project
Lipid nanoparticles (LNPs) are one of the most exciting medical technologies developed over the last few decades. These synthetic structures allow nucleic acids, such as oligonucleotides or mRNA, to be hidden in their core and delivered to cells within the body. Recently, LNPs formed the underlying biotechnology for both the Pfizer-BioNTech and Moderna COVID-19 vaccines. RNA is a novel therapeutic modality, which promises benefits in both vaccines and gene therapy, particularly within cancer therapy. LNPs offer one such route for delivery of targeted RNA therapies that can exploit oncogenic signalling within cancer cells. Currently, LNPs predominantly target the liver and LNP formulations are being developed for extra-hepatic delivery. How LNP formulation and 3D morphology can be tuned to promote tissue-specific RNA delivery for cancer therapy is currently unknown
This project will leverage advances in cryo-EM to understand the structure and morphology of LNPs, and how this relates to delivery to the bone marrow: the organ of origin of blood cancer. Unlike viral capsid based delivery structures, LNPs lack regular structure to average over either in a crystal or by imaging single particles, restricting structural analysis. Cryo-ET allows any structure to be subject to 3D analysis and is a rapidly emerging and developing field. Cryo-ET involves rotating cryogenically-frozen samples in an electron microscope to compute a detailed 3D morphology map. Using a microfluidic process at the industrial partner Labcorp, the student will prepare LNPs of different formulations incorporating reporter genes and therapeutically beneficial RNAs for leukemia. Cryo-ET will be used to resolve their structural organisation along with a range of other biophysical techniques. The 3D morphology will then be correlated with cell uptake and endosomal delivery to leukaemia cell lines. By the end of the project, we hope to have uncovered the interplay between LNP composition and structure, how this interplay allows efficient uptake of the LNP into cells, and how this knowledge can be used to optimise gene silencing therapies for leukaemia patients.
The project is a collaboration between the York Structural Biology Laboratory and the Centre for Blood Research (University of York), and the multinational biomedical company Labcorp (with sites in the York Biotech Campus and Harrogate). The successful student will benefit from a truly multidisciplinary experience, spanning industrial pharmaceutical development of LNP gene therapies for real-world application, leukemia stem cell biology and in vivo imaging techniques, and state-of-the art Cryo-ET and biophysical techniques. The student will receive a structured introduction to the project to leverage the abilities and mindsets of a dynamic, multidisciplinary supervisory team. Later, the close geographical location of the academic and industrial labs will allow the student to flexibly work between the sites as needed.
Benefits of being in the DiMeN DTP:
This project is part of the Discovery Medicine North Doctoral Training Partnership (DiMeN DTP), a diverse community of PhD students across the North of England researching the major health problems facing the world today. Our partner institutions (Universities of Leeds, Liverpool, Newcastle, York and Sheffield) are internationally recognised as centres of research excellence and can offer you access to state-of-the-art facilities to deliver high impact research.
We are very proud of our student-centred ethos and committed to supporting you throughout your PhD. As part of the DTP, we offer bespoke training in key skills sought after in early career researchers, as well as opportunities to broaden your career horizons in a range of non-academic sectors.
Being funded by the MRC means you can access additional funding for research placements, training opportunities or internships in science policy, science communication and beyond.
Supervisor pages
https://www.york.ac.uk/chemistry/people/jblaza/
https://www.york.ac.uk/biology/people/katherine-bridge/
https://www.york.ac.uk/biology/people/michael-plevin/
Research centres:
https://www.labcorp.com/
https://www.york.ac.uk/chemistry/research/ysbl/
https://www.york.ac.uk/biomedical-research-institute/centre-for-blood-research-at-york/about-us/
约克大学 MRC DiMeN Doctoral Training Partnership: Enhancing LNP-RNA delivery to leukemia cells through cutting-edge cryogenic electron tomography (cryo-ET)项目有没有奖学金，是不是全奖Phd招生，下面我们一起看一下【大学名称】Phd的奖学金资助情况
项目资助情况
iCASE Award: Industrial partnership project
Fully funded by the MRC for 4yrs, including a minimum of 3 months working with an industry partner. Funding will cover tuition fees and an enhanced stipend (£21,737 for 2024/2025) and project costs. We also aim to support the most outstanding applicants from outside the UK and are able to offer a limited number of full studentships to international applicants. Please read additional guidance here: View Website( https://www.findaphd.com/common/clickCount.aspx?theid=176384&type=184&DID=6625&url=https%3a%2f%2fwww.dimen.org.uk%2fapplications )
Studentships commence: 1st October 2025
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