UEA/FMH PGR Project Advertisement Request Form 2015/16
Supervisors should e-mail this completed form as a Word document to the Faculty AD PGR in order for their project to be considered for advertising. Handwritten documents will not be accepted. Letters confirming funding should be submitted electronically with this form where applicable. Faculty ADR will e-mail this form (as a Word document) and any attachments confirming funding to the PGR Office using . Receipt of this form in the PGR Office sent by the Faculty AD PGR will act as authorisation for the project to be advertised.
1. PRIMARY SUPERVISOR Title: Mr Name: Carl PhilpottWeb link (UEA only): https://www.uea.ac.uk/rhinology-group
Email address (UEA only):
2. SCHOOL £ HSC þ MED
DEPARTMENT OR GROUP
3. PROGRAMME £ MPhil þ PhD £ MSc by Research / þ full time £ part time
4. START DATE þ OCT £ JAN £ APRIL þ JULY YEAR : _2016______
5. TYPE OF PROJECT
þ Directly funded (Specifically awarded for this project either from a grant or directly
awarded studentship)
£ Competition funded (UEA, School, NRP, Research Council (inc DTP/DTG) studentship)
£ Self-funded
For Directly Funded and Self-Funded Projects, and also for projects short-listed for competition funding an advert will be placed on local institutional web sites and on FindaPhD.com. For these purposes please provide a “snappy” title and a summary of the project. Note: these should both be worded so as to attract potential applicants.
6. Project Title for Advertising: PhD in translational and personalised medicine: exploring biomarkers for Chronic Rhinosinusitis.
7. Project Text for Advertising * (maximum 300 words, Arial font size 11 please)
This PhD project will work ‘between the lab and the bedside’ to define a core set of inflammatory biomarkers for Chronic rhinosinusitis (CRS). CRS is a chronic inflammatory disease affecting 1 in 10 people in the UK where swelling in the nose and sinuses can lead to blockage and ultimately loss of smell. Laboratory work will involve analysis of cytokine responses and inflammatory signatures in material isolated from patients selected on the basis of clinical parameters allowing opportunities for the student to work alongside clinicans and patients. A large clinical trial, commencing in 2017, will explore the effectiveness of medical and surgical treatments for CRS patients and provide the student with the opportunity for the defined core set of biomarkers, to be analysed further in cell culture models, and including identification of any additional biological and clinical parameters not currently routinely collected.
The PhD student will be supervised by Mr Carl Philpott (Clinical Senior Lecturer) and Professor Tom Wileman (Professor of Infection and Immunity),in collaboration with otherBMRC colleaguesand working in conjunction with the clinical trial research team at Guys Hospital and University College London. The project is funded by the Sir Jules Thorne Trust and eligible students will receive a minimum tax-free yearly stipend of £14057 and university fees will be paid. This PhD is open to biological science or medical graduates; prior laboratory experience is desirable but not essential.
8. References, or indicative reading, to be included in advertising (up to 5) (Optional)
1. Hastan D, Fokkens WJ, Bachert C, Newson RB, Bislimovska J, Bockelbrink A, et al. Chronic rhinosinusitis in Europe--an underestimated disease. A GA(2)LEN study. Allergy. 2011 Sep;66(9):1216-23.
2. Fokkens WJ, Lund VJ, Mullol J, Bachert C, Alobid I, Baroody F, et al. European Position Paper on Rhinosinusitis and Nasal Polyps 2012. Rhinol Suppl. 2012 Mar(23):3 p preceding table of contents, 1-298.
3. Thamboo A, Thamboo A, Philpott C, Javer A, Clark A. Single-blind study of manuka honey in allergic fungal rhinosinusitis. J Otolaryngol Head Neck Surg. 2011 Jun;40(3):238-43.
4. Akdis CA, Bachert C, Cingi C, Dykewicz MS, Hellings PW, Naclerio RM, et al. Endotypes and phenotypes of chronic rhinosinusitis: a PRACTALL document of the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma & Immunology. J Allergy Clin Immunol. 2013 Jun;131(6):1479-90.
5. Elmorsy S, El-Naggar MM, Abdel aal SM, Abou-elela MA. Sinus aspirates in chronic rhinosinusitis: fungal colonization of paranasal sinuses, evaluation of ICAM-1 and IL-8 and studying of immunological effect of long-term macrolide therapy. Rhinology. 2010 Sep;48(3):312-7.
9. PROJECT DESCRIPTION
(To be completed ONLY when requested to assist with short-listing for competition funded projects. This text should include necessary background, a clear description of the aims and objectives of the project, and an indication of the scientific training that the student could expect from the project. max 900 words – Font, Arial 11pt)
Background
Chronic rhinosinusitis (CRS) represents a common source of ill health; 11% of UK adults report CRS symptoms in a worldwide population study(1). Symptoms include nasal obstruction, nasal discharge, facial pain, anosmia and sleep disturbance with a major impact on quality of life. The European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS)(2) has now defined rhinosinusitis the condition on clinical grounds based on the presence of these characteristic symptoms, combined with objective evidence of mucosal inflammation and/or radiological findings. CRS is divided into those with polyps (CRSwNPs) and without polyps (CRSsNPs). This division has been broadly based up the pathophysiological themes within these two main subgroups, either with a predominantly eosinophilic or neutrophilic inflammatory infiltrate respectively but this is very rudimentary. CRS endotypes represent a subtype of the condition defined by a distinct functional or pathobiological mechanism. Clinically practice is variable both in terms of medical and surgical treatment but there is increasing evidence that different CRS endotypes can be characterised by differences in responsiveness to different treatments, including intranasal corticosteroids, biological agents and Manuka honey(3). It is likely that these differences reflect differing pathophysiology between cases and are based on specific cytokine signatures(4). Moving away from the concept of CRS as a single disease entity has the potential for more effective treatment and better patient outcomes. The MACRO Programme, “Defining best Management in Adult Chronic RhinOsinusitis”, is being funded by NIHR at £3.2 million for 7 years commencing in September 2016 and with a clinical trial (workstream 2) commencing with a pilot in September 2017. The trial will assess the effectiveness of both clarithromycin for 3 months and endoscopic sinus surgery.
Hypothesis
By assessing biological and clinical parameters in patients with CRS, can we enable a clearer definition of potential disease endotypes and their relationship to the clinical phenotypes and subsequent treatment?
Aims and Objectives
· To explore the possibility of biological signatures using currently identified biomarkers (from the literature) in specific CRS patient groups that correlate with clinical parameters and outcomes in terms of response to treatment
· To test the in vitro effect of clarithromycin on cytokine responses in epithelial cell cultures
· To determine the effect of storage techniques on cytokine measurement and thus the necessary means of storage during the MACRO Programme Grant trial
· To specify a core set of biomarkers that should be analysed further during the course of the MACRO Programme Grant trial including identification of any additional biological and clinical parameters that are not routinely collected
Methods
The PhD student will be based at UEA using facilities in the Biomedical Research Centre and in Norwich Medical School. A literature search will be conducted to explore the latest evidence for CRS endotypes and relevant biomarkers that should be used. With approval from the UEA Research Ethics Committee, access will be granted to the existing repository of approximately 100 specimens of nasal polyps and mucus held at the Norfolk & Norwich University Hospital tissue bank. The biomarkers with the greatest potential to predict response to treatment identified from the literature review will be analysed from the banked specimens and by correlating this with clinical outcomes that will be derived from the James Paget University Hospital Rhinology database; further fresh tissue will be requested for some of the work using cell cultures. Once refined, the biomarkers selected will then be used in conjunction with patients entering a clinical trial as part of the MACRO Programme Grant led by Carl Philpott and Claire Hopkins.
The choice of biomarkers will be based on the literature search as well as prior experience and knowledge of chronic inflammatory conditions(2). IL-1β, IL-6, IL-8, IFN-γ , IL-17A, are pro-inflammatory cytokines generated predominately by macrophages and neutrophils, G-CSF IL-13, TGF-β affect T-helper cell polarisation and inhibit the production of pro-inflammatory cytokines, IL-5 stimulates B-cell growth and immunoglobulin secretion while IL-17A, IL-25, IL-33 are important for regulation of innate type II lymphoid cells which a have been implicated recently in allergy. MIP-1β, and GM-CSF stimulate recruitment of macrophages, while staphylococcal exotoxins-specific IgE and high polyclonal IgE levels are thought to be important precipitating factors of some cases of CRSwNPs. This combination of markers will allow us to stratify patients into those with predominantly pro-inflammatory phenotype (IL-1β, IL-6, IL-8, IFN-γ , IL-17A), possibly indicating macrophage-neutrophil involvement (MIP-1β, and GM-CSF), patients with changes in acquired T and B-cell meditated immune responses (eg: G-CSF IL-13, TGF-β) and those where disease may be underpinned by allergic reactions (eg: IgE, IL-17A, IL-25, IL-33). The nasal polyp tissue or nasal mucus will be processed by homogenization, centrifuging of suspensions followed by storage at -80°C until analysis for cytokines is performed. Supernatants will be assayed for the above cytokines using cytometric bead array flex sets (Proteome Profiler Human XL Cytokine Array) and data will be gained by flow cytometric analysis using a flow cytometer with BD CFlow® Software. As it is possible that storage of the current samples in the biorepository may have an effect on the cytokine stability, this preliminary work will also compare the yield with freshly harvested tissue and help optimise the storage requirements within the trial. Using confluent epithelial monolayers from CRS patients’ fresh sinus epithelial tissue grown in vitro, a further analysis would be performed before and after exposure to clarithromycin(5). The cytokine response between phenotypes (CRSwNPs, CRSsNPs) and between identified endotypes will be compared.
Analysis of the preliminary data will then be undertaken and the results reviewed by the MACRO team as part of the Programme team meetings. Analysis of electronic health records in Workstream 1 of the programme grant will also enable any modifications to the data collection required within the trial of both clinical and biological data to help define CRS endotypes further, ensuring the necessary resources are present and enable appropriate consent from trial participants. A control population will be sought from a parallel clinical trial of septoplasty where patients with CRS will be excluded. Further funding will be sought as appropriate for further work on the biological data collected during the trial including any additional techniques required (e.g. PCR, microarrays) and relevant consumable and staff costs. This will allow the PhD student to then continue the work into the trial, refining biological sample and clinical data collection during the pilot.
Projected outputs
With the resources of the Biomedical Research Centre at the University of East Anglia to hand, the student will have an excellent opportunity to undertake crucial work to stratify patient groups and thus take a step further towards developing personalised medicine for CRS. Aside from completion of the PhD, the student will be expected to publish findings in peer reviewed immunology, respiratory and ENT journals and to contribute to the wider development of the MACRO Programme in team meetings. He/she will be expected to present their work at at least one national and one international conference within Otorhinolaryngology or related specialties. The unique potential to run this project in parallel to a major national body of research funded by NIHR will strengthen its contribution to stratified medicine which is likely to reduce the impact of chronic diseases on precious NHS resources in the future.
10. FUNDING STATUS (required for advertisements on UEA website and FindaPhD.com)
þ Directly Funded Project (UK Students Only) (this means funding has been confirmed specifically for this project either from a grant or directly awarded studentship, including part faculty/part externally funded projects)
£ Directly funded Project (European Students Only) (this means funding has been confirmed specifically for this project either from a grant or directly awarded studentship, including part faculty/part externally funded projects but is open to UK/EU applicants only)
£ Directly funded Project (Students Worldwide) (this means funding has been confirmed specifically for this project either from a grant or directly awarded studentship, including part faculty/part externally funded projects and is open to any applicant)
£ Competition Funded Project (UK Students Only) (this means that this project is competing for funding, e.g. School or UEA funding, NRP studentship, Research Council (inc DTP/DTG) studentship)
£ Competition Funded Project (European Students Only) (this means that this project is competing for funding, e.g. School or UEA funding, NRP studentship, Research Council (inc DTP/DTG) studentship)
£ Competition Funded Project (Students Worldwide) (this means that this project is competing for funding, e.g. e.g. School or UEA funding, NRP studentship, Research Council (inc DTP/DTG) studentship)
£ Self-Funded Students Only (only students with their own means of support need apply)
For self-funded studentships, please go directly to box 12.
11. For DIRECTLY-FUNDED or COMPETITION-FUNDED studentships, please provide the information requested below: (N.B. Several may apply)
a) Source of funding £ Faculty Part Funded
þ External body (please specify, give name of partner, charity etc.)
__Sir Jules Thorne Trust______
£ CASE Award (if CASE or Industrial – give name of partner, e.g. Industry Partner, Research Council)
£ Other, please detail ______
b) Length of studentship (funded period) ___3 years______
NB. 3 year studentships have a (non-funded) 1 year ‘registration only’ period
c) Conditions of funding
Within two months following the end of the first and second years, the Trust should be provided with a brief report on the progress of the research project, signed by both the student and the Senior Clinical Lecturer. Within three months of the conclusion of the PhD project a report of the work should be submitted to the Trust. Copies of publications should be provided, together with details of further publications envisaged, and other achievements.
d) Amount of funding
(i) Fees _____£12,156.00______
(ii) RTSG/Bench fees* £1000/year
e) Other relevant funding Information
Consumables £27000
Important Note * - Please attach a copy of your grant award letter/RGN paperwork that includes details of awarded funding. Where there is a CASE partner please also attach confirmation of the award from the partner.
þ Award letter attached £ CASE partner award details attached
12. ENTRY REQUIREMENTS
a. acceptable first degree (please indicate acceptable first degree subject areas e.g. Health related subject etc, list all that apply).
MB BS or equivalent, BSc
b. The standard minimum entry requirement is 2:1 or above or a Masters degree. If your project requires a 1st, please state here :
13. a) How many PGR students are you currently Primary supervisor for?
1st year _2___ 2nd year ____ 3rd year ____ 4th year ____ Other years _____
b) How many offers are currently pending with you as named primary supervisor? ___
c) Date of last Supervisor Training attended ___May 2014______
14. KEYWORDS
To enable advertising on FindaPhD.com (the keywords below are the only ones accepted by FindaPhD.com)
Biological & Medical Sciences Social Sciences & Health Sciences
* Agricultural Sciences * Anthropology
* Biochemistry * Asian Studies
* Bioinformatics * Development Studies
* Biomedical Engineering * Economics
* Biophysics * Education
* Biotechnology * Gender & Sexuality
* Botany / Plant Science * Health Sciences
* Cancer / Oncology * Law
þ Cell Biology / Development * Middle East & African Studies
* Dentistry * Modern languages & Linguistics
* Ecology & Conservation * Philosophy
* Endocrinology * Political Science & International Studies
* Evolution * Public Health & Epidemiology
* Food Science / Nutrition * Social Psychology
* Genetics * Social Work, Social Policy & Administration
þ Immunology
* Marine Biology
* Medical / Biomedical Physics
þ Medical / Clinical Science
* Microbiology
* Molecular Biology
* Neuroscience / Neurology
* Obstetrics, Gynaecology & Reproduction
* Parasitology
* Pathology
* Pharmacology / Toxicology
* Physiology & Sports Science
* Psychology & Psychiatry
* Public Health & Epidemiology
* Structural Biology
* Veterinary Medicine
* Virology
* Zoology / Animal Science
For completion by PGR Office only
Application deadline:
For PGR Office use:
Interview Panel:
Chair: (AD PGR or School PGR Director)
Primary Supervisor:
Panel Member 1:
Panel Member 2:
(If required)
2