Three PhD Scholarships: High Throughput Approaches to Decipher the Role of Human Endothelial Cells in Chronic Disease

University of Hull - School of Life Sciences and Hull-York Medical School

To celebrate the University's research successes, the University of Hull is offering a full-time UK/EU PhD Scholarship or International Fees Bursary for candidates applying for each of the three following research projects from the “High throughput approaches to decipher the role of Human Endothelial Cells in Chronic Disease” Cluster:

  • PhD Project 1 - Discovery and characterisation of novel (lymph)angiogenic regulators of human endothelial cell function in drug resistant cancers.
  • PhD Project 2 - Novel molecular regulators of human endothelial cell barrier function in cardiovascular disease.
  • PhD Project 3 - Genomics of human endothelial cell function in chronic disease.

Keywords: human endothelial cell, big data, genomics, proteomics, cancer, cardiovascular disease.

Place: University of Hull, Faculty of Health Sciences, School of Life Sciences and Hull-York Medical School.

Closing date: Thursday 8th February 2018.

Studentships start: 17th September 2018.

Persons specifications: 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.

Cluster Summary

The opportunity to engage in fully funded three-year PhD study at the University of Hull from September 2018 is available for three exceptional candidates with an interest in biomedical research in the fields of human cell biology, molecular biology and/or vascular biology, as well as an ambition to become a next generation biomedical or clinical laboratory professional.

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.

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. For details about individual projects and application process, please refer to the information provided below.

  • PhD Project 1 Summary

Discovery and characterisation of novel (lymph) angiogenic regulators of human endothelial cell function in drug resistant cancers.

Reference: Endo_Big Data_1

Supervisor: Dr. Leonid Nikitenko

http://www.hull.ac.uk/Faculties/staff-profiles/Leonid-Nikitenko.aspx

Contact for informal enquiries: l.nikitenko@hull.ac.uk

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.

 

  • PhD Project 2 Summary

Novel molecular regulators of human endothelial cell barrier function in cardiovascular disease.

Reference: Endo_Big Data_2

Supervisor: Dr. Francisco Rivero

http://www.hyms.ac.uk/dynamic-pages/staff-profile?Name=Francisco_Rivero_Crespo&PID=4563

Contact for informal enquiries: francisco.rivero@hyms.ac.uk

Endothelial cell dysfunction is the hallmark of the development of cardiovascular diseases, including atherosclerosis, a pathology that causes some of the very costly medical conditions. Various stress stimuli, such as high LDL levels in the blood, can contribute to this process by causing an inflammatory response that triggers changes in gene expression, disruption of the endothelial cell barrier, increased permeability and, ultimately, irreversible changes in blood vessel structure. The early key signalling pathways of this process are unknown.

Stress commonly affects key signalling pathways that ensure the maintenance of the endothelial barrier. Recently, we have identified novel interacting partners of a one of the key components of the phosphorylation/de-phosphorylation cycle that relays signals from the plasma membrane to the contractile machinery and ultimately regulates the endothelial cell barrier. The PhD student will apply genomics and proteomics approaches to study primary human endothelial cell response to various stress stimuli, and will use computational biology approaches with an overall aim to identify key early regulators of endothelial dysfunction. This knowledge will help discover and fully characterise intracellular pathways and gene expression changes modulated by the novel interactions we have found and will contribute to the development of the strategies to diagnose, prevent or therapeutically manage atherosclerosis and other chronic cardiovascular conditions.

Apply: http://www.hyms.ac.uk/postgraduate/how-to-apply/applying-for-postgraduate-study

  • PhD Project 3 Summary

Genomics of human endothelial cell function in chronic disease.

Reference: Endo_Big Data_3

Supervisors: Dr. Katharina Wollenberg Valero and Dr. Leonid Nikitenko

www.hull.ac.uk/katharinawollenbergvalero 

http://www.hull.ac.uk/Faculties/staff-profiles/Leonid-Nikitenko.aspx

Contacts for informal enquiries: k.wollenberg-valero@hull.ac.uk or l.nikitenko@hull.ac.uk

Endothelial cells play a key role in the physiology of every single organ in human body and in the pathogenesis of several chronic diseases. This research project will combine in vitro and in silico approaches, including human cell biology, genomics and bioinformatics techniques to understand molecular mechanisms underlying endothelial cell function in cancer and cardiovascular disease. This studentship constitutes a key position within the Cluster. This research project will combine insights from cell culture experiments utilising primary human endothelial cells isolated from blood and lymphatic vessels, with the generation and analysis of gene expression using microchip and next generation sequencing technologies.  

The PhD student will analyse our expanding library of gene expression datasets and generate novel ones. They will develop expertise in biomedical data science through laboratory work and bioinformatics, learning career-relevant skills and techniques. Bioconductor will be used as the industry standard for biomedical analysis of genomic, transcriptomic and array data. This PhD scholarship offers exciting and invaluable work experience aimed at enhancing professional development of the individual with an expertise in human cell biology and an interest in genomics and bioinformatics. The successful candidate will receive extensive training in the three challenges of big data science related to this project (data flow, data analysis, and data curation) via visits to University College London Cancer Institute and Wellcome Trust Centre for Human Genetics in Oxford, conference/workshop participation, as well as supervision by the support team of the University of Hull’s VIPER high performance computer and UCL bio(medical)informatics team.

For further particulars about individual projects, prospective candidates are encouraged to contact supervisors. Please include project reference, your research interests, experience and full CV in your email.

To apply for these Scholarships please click on the Apply button below.

http://www2.hull.ac.uk/student/admissions/postgraduate/phd-scholarships.aspx

Full-time UK/EU PhD Scholarships will include fees at the ‘home/EU' student rate and maintenance (£14,553 in 2017/18) for three years, depending on satisfactory progress.

Full-time International Fee PhD Studentships will include full fees at the International student rate for three years, dependent on satisfactory progress.

PhD students at the University of Hull follow modules for research and transferable skills development and gain a Masters level Certificate, or Diploma, in Research Training, in addition to their research degree.

Successful applicants will be informed of the award as soon as possible and by 2nd April 2018 at the latest.

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Type / Role:

PhD

Location(s):

Northern England