About this project
This cluster of three interlinked projects will be focussed on defining the molecular mechanisms and signalling pathways that regulate human endothelial cell function in chronic diseases following our recent discoveries at the University of Hull. The key pathologies to be studied are therapy-resistant cancers and cardiovascular disease. This research initiative involves eight academics with research expertise in basic cell biology, clinical research, oncology and respiratory/cardiovascular disease. The goal of this collaborative network is to establish novel genomic and proteomic big data pipeline that can be used by the global scientific community to decipher human endothelial cell biology in chronic diseases for their improved diagnosis and treatment.
Three projects offer prospective students an opportunity to work within an interactive and dynamic environment at the School of Life Sciences and the Hull-York Medical School, which house state-of-the-art laboratory facilities and resources for undertaking biomedical research. Students will receive training in laboratory techniques such as confocal microscopy, protein biochemistry, immunohistochemistry, RNAi-mediated gene knockdown, whole genome analysis and clinically relevant three-dimensional models of human endothelial cell function in chronic diseases. They will also use the University of Hull High Performance Computer VIPER (largest supercomputer in the North of England) and big data computational approaches, including bioinformatics, and become part of a wider collaborative network that involves researchers based at the University of Oxford and University College London. The generous research budget to cover laboratory costs (£9000) and opportunities to travel for collaborations and other meetings or conferences will be provided in addition to the stipend to all three successful candidates.
The University of Hull offers postgraduates the opportunity to undertake a three-year research project whilst enhancing professional development and research skills through a comprehensive training programme. You will join a vibrant research community and will be supervised by the experts in the fields of cancer and cardiovascular biology, as well as supported by the rest of the Cluster members. Three PhD students will become members of our rapidly expanding postgraduate community of next generation researchers, and supported by regular laboratory meetings, seminars and journal clubs. All students will undertake a three-month professional start-up training at the beginning of their study. The PhD scholarship scheme and three projects offer exciting and invaluable work experience designed to enhance professional development. Full support and advice will be provided by the supervisors and the cluster advisory committee.
Discovery and characterisation of novel (lymph) angiogenic regulators of human endothelial cell function in drug resistant cancers.
Supervisor: Dr. Leonid Nikitenko
In cancer, the cross-talk between the endothelial and tumour cells is essential for (lymph)angiogenesis (growth of new blood and lymphatic vessels) and metastasis (tumour dissemination to distant organs). Both of these chronic disease processes are directly associated with the poor prognosis and survival outcomes in advanced cancer patients. Identification of the underlying molecular mechanisms responsible for (lymph)angiogenesis and metastasis is essential for the development of new cancer diagnostics and therapies.
The successful PhD candidate will use two- and three-dimensional in vitro models of primary human endothelial cells and clinical samples to characterise recently identified molecular regulators of blood and lymphatic endothelial cell function in renal carcinoma and soft tissue sarcoma, which are both highly resistant to current conventional and targeted therapies. The PhD student will perform gene expression analysis and bioinformatics to dissect the downstream signalling pathways for these molecular regulators, leading to the discovery of novel molecular mechanisms involved in cancer progression. They will use computational biology approaches to identify candidate genes involved in drug resistance, focusing on secreted proteins and cell surface receptors as alternative targets. Two- and three-dimensional model systems that closely represent human tissue will be used to validate candidate target genes for therapeutic intervention, with the ultimate goal of guiding drug design. The project will also incorporate lab-on-a-chip technology developed at the University of Hull to test the therapeutic effect of newly developed drugs on human vessels for the purpose of guiding the design of safe clinical trials.
You are strongly advised to contact a potential supervisor and to discuss your research proposal, well before you submit an application. Please refer to the Faculty of Health Sciences research pages.
For further information regarding this project please contact Dr Leonid Nikitenko
To celebrate the University's research successes, the University of Hull is offering a full-time UK/EU PhD Scholarship or International Fees Bursary.
Applicants with at least an upper 2nd class honours undergraduate degree, or equivalent, in cell or molecular biology and/or vascular biology (or related discipline) and/or bioinformatics, together with relevant research experience, are encouraged to apply. It is anticipated that the successful applicant will have a 1st class honours undergraduate degree or Masters level qualification.
Prospective students are expected to have excellent communication skills and be good team players, as their independent projects will jointly contribute to Cluster research goals. Very strong work ethic and good experimental skills, the ability to think creatively and pursue independent research, excellent writing skills and fluency in English are also anticipated. Good analytical/mathematical and computational skills, preferably with some knowledge of statistical approaches, would be an advantage. We encourage applications from students whose backgrounds are traditionally underrepresented in STEM fields.