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PhD Studentship: Taxonomy, Treatment, Targets and Remission: Identification of the Molecular Mechanisms of non-response to Treatments, Relapses and Remission in Autoimmune, Inflammatory, and Allergic Conditions

Human Development and Health

Location:  Southampton General Hospital
Closing Date:  Monday 28 October 2019
Reference:  1188719AF

Lead Institute / Faculty: Faculty of Medicine (HDH)

Main Supervisor: Professor Graham Roberts

Other members of the supervisory team: Prof Ratko Djukanovic (CES)

Duration of the award: Three years, full time

Project description: 

Airway diseases such as asthma and chronic obstructive pulmonary disease (COPD) are common, chronic and collectively impose a substantial healthcare burden. While treatments are available, response and disease progression is unpredictable in individual patients. Molecular profiling and integration of multi-omics data is a novel approach to stratify individuals with clinically heterogeneous diseases, not only with a view to reclassification but also to identify the molecular basis of their pathogenesis and potential new biomarkers of disease progression and severity. 3TR is a highly integrated and transdisciplinary European consortium that plans multi-dimensional molecular analysis of multiple sample types collected longitudinally from homogeneously recruited patient cohorts suffering from seven different autoimmune, allergic and inflammatory diseases. This high-resolution multi-omics analysis of individualised disease trajectories will facilitate the stratification and identification of molecular patterns that better predict response or non-response to therapy. The major aim of the consortium is to identify solid biomarker signatures as well as molecular pathways and mechanisms linked to response and non-response to therapy. 

This PhD studentship sits within this European collaborative project and is based in the University of Southampton Faculty of Medicine. It will focus on the determination of therapeutic response in asthma and COPD looking at clinical, biological and patient reported outcomes. 

The first part will involve the identification of relevant biomarkers. These may include biomarkers, clinical, biological and imaging aspects. The European Respiratory Society methodology approach, based on GRADE, will be used. A systematic review will be undertaken of the evidence using a patient, intervention, comparison, and outcomes (PICO) format where appropriate. Where this is not possible, a pragmatic narrative review of the evidence will be undertaken, using a Delphi process where necessary. All questions will then be placed into an evidence to decision framework to make the most appropriate recommendations. 

The second part will focus on assessing the patient centeredness of existing patient reported outcomes and quality of life measurements in asthma and COPD. This will involve working with the European Respiratory Society (ERS), European Lung Foundation (ELF) and European Federation of Allergy and Airways Diseases Patients’ Associations (EFA). It is expected that the first and second parts will proceed in parallel during year one. 

The third part focuses on the definition of response with asthma COPD therapies. Existing definitions of outcomes and definition of response will be surveyed in guidelines and publications. A final definition of response in asthma and COPD will be produced to include patient-centred outcomes, physiological and biological measures of response. Consideration will be made to align the measures of response across the disease areas. Definitions for a response that indicates disease remission will be included, such as short-term and long-term remission. It is expected that these definitions will be key in designing future studies that assess disease modification. This third part will be expected to follow on from the first two parts in year two.

The fourth part in year three will be decided in conjunction with the student. It could involve a development of the first three parts or be more methodologically focused. 

The project will involve liaison with project partners from across Europe. Some of this work will be undertaken at project meetings, other activities will be undertaken over the internet. The student would join this multidisciplinary team. Training will be given in airway disease and therapeutics, the synthesis and critical evaluation of primary research, qualitative methodology and working with patient groups. 

The University of Southampton and University Hospital Southampton provide an excellent research environment. The PhD student will have access to a number of benefits in addition to the University of Southampton and Faculty of Medicine opportunities; training support, mentorship scheme, a multidisciplinary research environment as well as opportunities to attend courses and conferences. 

Candidate requirements:

Candidates should have, or be expected to achieve, a first-class honours or 2:1 degree qualification (or equivalent) in a relevant discipline. A relevant Master’s degree would be desirable but not a prerequisite. 

Please contact:  Professor Graham Roberts g.c.roberts@soton.ac.uk

Person Specification: See below

Funding information:
 
Funding is providing for a student stipend (1st year: £14,943.50; 2nd year: £15,167,75; 3rd year £15,395.00). Funding is also provided to cover University fees (1st year: £4,308.00; 2nd year: £4,372.75; 3rd year £4,438.50; UK/EU & Channel Island rates). Student’s contract will include the amount of waived fees as part of their remuneration. 

Administrative contact and how to apply:

Please complete the University's online application form, which you can find at 

https://studentrecords.soton.ac.uk/BNNRPROD/bzsksrch.P_Login?pos=7209&majr=7209&term=201920

You should enter Professor Graham Roberts as your proposed supervisor. To support your application provide an academic CV (including contact details of two referees), official academic transcripts and a personal statement (outlining your suitability for the studentship, what you hope to achieve from the PhD and your research experience to date).

Informal enquiries relating to the project or candidate suitability should be directed to Professor Graham Roberts (g.c.roberts@soton.ac.uk).

Closing date: Monday 28th October 2019

Interview date:  Thursday 7th November 2019



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