The role of environmental factors in cystic fibrosis disease progression

 

Currently open for applications, deadline Thursday 29 June 2017 (23:59 GMT). 

Supervisors: Anna Hansell (SAHSU), Frédéric Piel (SAHSU) and Rebecca Cosgriff (CF Trust)

The Cystic Fibrosis Trust (https://www.cysticfibrosis.org.uk/) and Imperial’s MRC Doctoral Training Programme (DTP, https://www.imperial.ac.uk/mrc-dtp-studentships) are co-funding two PhD studentships on cystic fibrosis and environmental factors to be hosted at the Small Area Health Statistics Unit (SAHSU, http://www.sahsu.org/), within the MRC-PHE Centre for Environment & Health (http://www.environment-health.ac.uk/) at Imperial College London.

Project summary

The projects will focus on analyses of the CF Registry data in relation to environmental factors, including air pollution, to rigorously quantify possible causative interactions, with a particular focus on respiratory disease. As for many projects conducted within SAHSU, this will require the use of detailed geographical information (i.e. address or postcode level) to enable accurate exposure assignment for all patients in order to conduct detailed analyses and estimate each patient’s individual exposure to a range of environmental factors known or suspected to influence disease progression.

Data protection and information governance are key priorities for SAHSU (see below) and we have experience in assigning environmental exposures to address or postcode level working with a number of UK cohorts including ALSPAC, UK Biobank and the 1946 birth cohort. A careful assessment of the most appropriate datasets for individual exposure to a range of environmental factors (e.g. observed at nearest monitoring stations vs modelled at all locations) will be conducted.

The projects will involve conducting a systematic review and meta-analysis as well as using specific epidemiological tools for small-area studies and environmental exposure analyses, such as time-series analyses, geographical information systems (GIS) and statistical methods. The projects will be conducted in close collaboration with the UK CF Trust and the successful candidates will be encouraged to build on preliminary collaborations established in the UK and internationally.

Expected outcomes

Successful candidates will be expected to produce excellent academic research to be presented at national and international conferences, and published in peer-reviewed journals (preferentially in open-access). They will actively engage with the community of scientists and clinicians involved but also, importantly, with the Cystic Fibrosis Trust and the community of patients and their relatives, including through active participation at the Annual Meeting of the CF Trust. Translating research results into useful advice for individuals with CF will be the ultimate outcome of these projects. 

Background

Cystic fibrosis (CF) is a life-limiting inherited condition caused by a faulty gene that controls the movement of salt and water in and out of cells. It causes mucus to gather in the lungs and digestive system and creates a range of challenging symptoms including problems with lung function, which can drop to less than 20% of the value expected in someone with fully functioning lungs; with the digestive system, including failure of the pancreas; and chronic bacterial infections. Estimates of disease incidence are around 1 in 3,000 live births in persons of northern European descent, with Ireland having the highest incidence at 1 in 1,400 live births. Incidence varies according to race and ethnicity; only 1 in 4,000 to 10,000 Latin Americans and 1 in 15,000 to 20,000 African Americans have cystic fibrosis, with even lower incidence rates in people of Asian background. In addition, millions of asymptomatic people carry the faulty gene (2.5 million in the UK, corresponding to 1 in 25 individuals). Each week five babies are born with cystic fibrosis, and two CF patients die.

More than half of the CF population in the UK will now live past 41 – compared to a life expectancy at birth of about 80 years for normal individuals. Improved care and treatments continue to improve the survival and quality of life of CF patients. There is currently no cure for cystic fibrosis but many treatments are available to manage it, including physiotherapy, exercise, medication and nutrition. Marked variations still exist in CF health outcomes. The clinical course of CF for any individual with CF is determined by the interaction of genetic factors (including CFTR and modifier genes) and non-genetic factors. The latter include the physical environment (e.g. environmental tobacco smoke, outdoor pollution, and pathogenic microorganisms), the sociodemographic, cultural, and family context (which mediates stress, social support, and disease self-management skills), and variations in delivery and acceptance of healthcare treatments. Ongoing efforts are currently focusing on genetic factors influencing disease progression. Although a better understanding of non-genetic factors could provide a more immediate way of improving disease outcomes, this area of research is currently neglected.

How to Apply: 

In the first instance, please send your CV and a personal statement explaining your interest in this research area and why you would be suitable for this studentship, before the deadline of Thursday 29 June 2017, 23:59 GMT. They should be sent by email to Dr Fred Piel (f.piel@imperial.ac.uk). 

You may be asked to complete a longer application form at a later stage, if so we will provide this along with further details. 

Eligibility 

The eligibility criteria below match those of the Medical Research Council (MRC) and MRC-DTP (http://www.imperial.ac.uk/mrc-dtp-studentships/eligibility-criteria/).

Applicants are expected to hold a first class or upper second class Honours degree (or its equivalent) in an appropriate science subject from a recognised university with a strong quantitative/ computational background in biostatistics, epidemiology, data sciences, bioinformatics or mathematics and also have a Masters degree (with minimum merit pass or equivalent) or equivalent research experience by the start of their PhD.

To be eligible for a full award, a student must have:

  • settled status in the UK, meaning they have no restrictions on how long they can stay.
  • been ‘ordinarily resident’ in the UK for three years prior to the start of the studentship. This means they must have been normally residing in the UK (apart from temporary or occasional absences).
  • not been residing in the UK wholly or mainly for the purpose of full-time education (this does not apply to UK or EU nationals).
EU fees-only studentships

To be eligible for a fees-only award, a student must be ordinarily resident in a member state of the EU, in the same way as UK students must be ordinarily resident in the UK.This covers the cost of the university fees, conference fund and Research Training Supplement Grant, but does not include the monthly stipend. 

 

Host and funding institutions 

The UK Cystic Fibrosis Trust

The Cystic Fibrosis Trust sponsors and manages the UK Cystic Fibrosis Registry, a secure centralised database containing health data records on consenting people with cystic fibrosis (CF) in England, Wales, Scotland and Northern Ireland. The UK CF Registry was set up in the late 1990s to centralise data from 58 CF centres and over 80 CF clinics and currently includes about 10,000 registered patients, i.e. 99% of the people with CF in the UK. The UK Cystic Fibrosis Registry is internationally recognised as one of the most successful disease registries worldwide.

The overall aim of the Registry is to achieve continuing improvements to the quality and safety of care; it achieves this by providing high-quality data and analysis, and by supporting research, including studies observing the safety of new drugs. The CF Trust also has a role in influencing government policy through demonstrating the value of disease registries.

Small Area Health Statistics Unit

The Small Area Health Statistics Unit (SAHSU) was established in 1987 following a recommendation from the Black Enquiry into the incidence of leukaemia in children and young adults near the Sellafield nuclear power plant for an organisation to coordinate centrally the monitoring of small area statistics around major installations producing discharges that might present a carcinogenic or mutagenic hazard to the public. In this way early warning of any untoward health effect could be obtained.

The Unit was initially established at the London School of Hygiene and Tropical Medicine but in 1996 transferred to Imperial College London. The Unit now forms a core part of the MRC-PHE Centre for Environment and Health held jointly between Imperial College London and King's College London set up in 2010.

The main role of SAHSU is to assess the risk to the health of the population from environmental factors by using routinely collected health and population data at a small area scale. To this end, SAHSU holds comprehensive computerised sets of health and demographic data and a range of environmental datasets at high spatial resolution.

Data safety and confidentiality are key components of the research conducted within SAHSU. SAHSU holds copies of various sensitive health datasets from the NHS, the ONS, and cancer registries. Data and analyses are conducted exclusively by approved staff on a secured private network compliant with the highest security and data confidentiality standards.

MRC-PHE Centre for Environment and Health

The MRC-PHE Centre for Environment and Health was formed in June 2009 as a partnership between Imperial College and King’s College London, funded by the Medical Research Council (MRC) and Public Health England (PHE). The Director is Professor Paul Elliott (Imperial) and the Deputy Director is Professor Frank Kelly (King’s). The Centre incorporates the UK Small Area Health Statistics Unit (SAHSU) at Imperial College, the Environmental Research Group (ERG) at King’s College London, in addition to bringing together leading researchers from four departments of the Faculty of Medicine at Imperial College (including the National Heart and Lung Institute), and researchers at King’s College, St George’s University of London and London School of Hygiene and Tropical Medicine.

The Centre is internationally recognised in research on environment and health along with providing vibrant cross-disciplinary research training. The Centre promotes novel cross disciplinary approaches, integrating individual-level and small-area analyses of environmental exposures and health, together with experimental data, biomarker and mechanistic studies, and analyses of large population cohorts. The formation of the Centre in 2009 catalysed a number of new research programmes which would not have otherwise occurred, and the renewal of Centre funding for a further five years in 2014 has allowed the Centre to build on its key strengths in multidisciplinary research in environment and health.

MRC Doctoral Training Programme

Imperial College’s Medical Research Council Doctoral Training Partnership (MRC DTP) Research Studentships enable graduates with excellent honours degrees to undertake a 3.5 year training programme, which includes a research project plus training in research methods and transferable key skills, leading to the submission of a doctoral thesis and the award of a PhD. The proposed projects, co-funded by the CF Trust, will be in line with the “Informatics for Health” strategic theme of the MRC DTP.

To be eligible, the candidates will need a first class or a good upper second class Honours degree (or equivalent) in an area relevant to their proposed field of research, and to demonstrate a settled status in the United Kingdom. Detailed guidance regarding residence eligibility is available in the residence eligibility requirements section of the MRC website (http://www.mrc.ac.uk/skills-careers/studentships/studentship-guidance/student-eligibility-requirements/).