The Identification and Characterisation of Biomarkers for the Earlier Diagnosis of Chronic Disease (5 PhD Scholarships)

University of Hull - The School of Life Sciences and The School of Mathematics and Physical Sciences

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 following projects.

Closing date: - Thursday 8th February

Studentships will start on 17th September 2018

Summary of Cluster

There is a worldwide need to identify biomarkers that are specific and enable the diagnosis of chronic disease at an earlier time point. In doing so we can treat patients before their disease affects multiple organs, enabling more effective treatment, extending patient survival and enhancing quality of life. We aim to develop non-invasive or minimally invasive tests to identify early pre-clinical disease changes in patients. This should improve patient outcomes with diminished side effects and decrease NHS treatment costs.

This cluster encompasses academic staff, based in both the School of Life Sciences and the School of Mathematics and Physical Sciences at the University of Hull, who are experienced in biomarker identification in difficult to treat diseases such as endometriosis (Guinn), therapy-induced cancer (Wade), cardiovascular disease (Beltran-Alvarez) and sarcoidosis (Hart). Our skills in state-of-the-art technologies such as lab-on-a-chip (Pamme) and spheroids (Pires), and our access to high tech equipment (mass spectrometry, phosphor-flow cytometry, transcriptomics) provide a unique opportunity to collaborate and form a UK cluster of excellence providing high quality training and mentorship to our PGR students.

PhD Project 1: Novel cardiovascular markers and therapies based on protein arginine methylation with Dr Pedro Beltran-Alvarez (P.Beltran-Alvarez@hull.ac.uk). For those students with an interest in biology and the biological basis of heart and cardiovascular disorders, you will join a young and friendly group passionate about post-translational modifications of proteins and how they change in response to disease states. You will create new knowledge and molecular tools to develop arginine methylation as a novel biomarker of cardiovascular disease (including myocardial infarction) using human samples from hospitals and state-of-the-art biochemistry and proteomics approaches. You will help deliver new diagnostics and therapeutics that could save the life of millions every year.

PhD Project 2: Identification of novel biomarkers in sarcoidosis with Dr Simon Hart (S.Hart@hull.ac.uk) and Dr Barbara Guinn (B.Guinn@hull.ac.uk). Sarcoidosis is a rare condition that leads to the development of patches of swollen tissue (granulomas) that affect the lungs, skin and other organs. We want to assess mTOR pathway activation markers, in tissue biopsies and blood samples, for their role as potential biomarkers in patients with sarcoidosis. Your biological based work will complement studies on a computational model of granulomatous inflammation, by feeding the in vitro experimental findings into the model. Techniques/skills used in this project would include immunohistochemistry of archive biopsy tissue, phospho-flow cytometry of freshly-isolated blood monocytes, transcriptomics of biopsy tissue and blood PBMCs and treatment of in vitro culture of human monocyte-derived macrophages with inhibitors.

PhD Project 3: Determination of the origins of endometriosis and identification of novel targets for therapy with Dr Barbara Guinn (B.Guinn@hull.ac.uk) and Dr Isabel Pires (I.Pires@hull.ac.uk). Endometriosis is a common condition that affects 1:10 women, and can cause pathologies in local and distant organs. Despite its commonality, the biological causes of this disease remain unclear. Symptoms can be severe and complications include infertility. The only current true diagnostic strategy, as well as the most effective treatment, is invasive laparoscopic surgery. Importantly, no specific clinical biomarkers for this disease exist. You will join a small but friendly lab team who are established in the field of biomarker identification and characterisation. The techniques you will use will include SEREX and 2D gel electrophoresis to help identify the proteins that are unique to endometriosis. In doing so we hope to determine the source of the cells that cause endometriosis and provide novel therapies for their destruction.

PhD Project 4: Identification of genomic biomarkers for therapy-induced cancer with Dr Mark Wade (M.Wade@hull.ac.uk). Therapy-induced solid tumours arise as a consequence of the treatment given for primary cancer. Although these malignancies have a well-defined aetiology, the molecular genetic alterations that define these cancers and drive carcinogenesis are not well understood. You will join an ambitious and friendly group aiming to identify and validate common molecular genetic alterations in therapy-induced solid tumours. The strategies used to achieve this aim will be varied, including genome-wide analysis of therapy-induced tumour samples to identify novel genetic alterations, focussed genomic analysis of samples to validate current and identified targets, and functional analysis of alterations in cell line models. Your work will identify alterations that will help to define the genomic landscape of therapy-induced tumours, act as biomarkers for the early detection of therapy-induced cancer, and aid the development of targeted therapeutic regimens.

PhD Project 5: Lab-on-a-chip platform for detection of early metastasis biomarkers with Dr Isabel Pires (I.Pires@hull.ac.uk) and Professor Nicole Pamme (N.Pamme@hull.ac.uk). Metastatic disease is responsible for 90% of cancer deaths. However, the identification of specific biomarkers for early metastasis or pre-metastatic alteration remains an area of unmet need. In this project we will develop an advanced on-chip platform to model tumour microenvironmental conditions driving metastatic disease. The project builds on current expertise in the biology and modelling of the tumour microenvironment (Pires) and the development of microfluidic devices (Pamme). We will incorporate 3D models of cancer (multicellular spheroids), in the well-controlled microenvironment of a microfluidic platform and analyse molecular and cellular components released from the spheroids using immunodetection or electrochemical sensors, as well as high throughput techniques such as Mass Spectrometry and RNA-sequencing. These strategies will allow the identification of novel molecular markers of early metastasis, ultimately to be translated as clinically relevant biomarkers. This exciting multidisciplinary project encompasses many varied technical skills and approaches, including cancer cell tissue culture (2D and 3D), transcriptomic and proteomic analysis, and cutting-edge bioengineering of microfluidic devices. The successful candidate will be expected to have a solid knowledge base in cell biology and molecular biology, and, ideally, some knowledge on cancer biology. The candidate must also show a willingness to work multi-disciplinary and embrace the area of microfluidic chip design.

Applicants should have at least a 2.1 undergraduate degree in biomedicine or a related discipline, together with relevant research experience. It is anticipated that the successful applicant will have a 1st class undergraduate degree or Masters level qualification.

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