JOB DESCRIPTION
Job Title:
Research Associate
Division:
National Heart and Lung Institute
Section:
Airway Disease and Airway Pharmacology
Job Family and Level:
Academic and Research, Level B
Salary Range:
£32,100 - £40,720 per annum
Responsible To:
Professor Ian M Adcock/Professor Fan Chung
Works closely with:
Dr Coen Wiegman
Location:
Royal Brompton Campus
Funding:
EU-IMI
Duration:
Fixed term until 28 September 2014
Project Title:
A transferable model of steroid resistant asthma
Research Programme
The objectives for the in vivo part of WP6 within UBIOPRED is to (i) develop in vivo models that
mimic aspects of severe asthma and human clinical models and (ii) compare hand prints obtained in
human severe asthma and in clinical models of disease with in vivo studies to determine optimal
overlap with clinical sub-phenotypes, and (iii) optimise in vivo models to possess the molecular and
cellular mechanisms that operate in clinical severe asthma thereby enhancing the predictive
capacity of these models.
This programme will use high-dimensional biology techniques to investigate various animal models
for the study of severe asthma and to assess their predictive value for the identification of novel
targets and early proof of concept for new asthma drugs. The programme uses both unbiased and
focused (selective) ‘omics approaches including transcrioptomics, lipidomics and proteomics along
with standard lung functions and inflammatory mediator analysis to enable integration using
Transmart.
The Innovative Medicines Initiative (IMI) strategic agenda identified the need for:
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Disease models to further knowledge of pathways driving exacerbations and to enable
assessment of intervention, and specifically
Identification and validation of new preclinical models to facilitate translational research of
novel agents for severe asthma, including proof of pharmacology, mechanism and PK/PD
including the strategic use of animal models to identify relevant biomarkers that can be
extended to human models in vitro and to in vivo studies of human disease
A major bottleneck in drug development for asthma is the inability of pre-clinical models to
accurately predict clinical efficacy. U-BIOPRED will use integrated biomarker profiles in conjunction
with a systems biology approach that will ‘allow a rational and well informed choice of molecular
target and animal models that demonstrate pharmacological action and predict efficacy’ as indicated
by the IMI SRA. Animal models will be developed that better reflect the molecular and cellular
mechanisms involved in the progression of severe asthma and during viral exacerbation.
Inadequacies in the predictiveness of in vivo models of asthma are ‘responsible for a significant
proportion of the drugs that have failed in clinical trials to meet their endpoints’. As part of this
strategy we will use patient handprints and those obtained in the clinical viral challenge model of
exacerbations to guide the development of improved in vivo models of severe asthma.
The human model of exacerbation and loss of control will be mirrored by viral challenge in a chronic
house-dust mite exposed mice that more closely resemble human asthma and in FCA-HDM
models. Animal models are an important aspect of drug development as they enable candidate
selection and proof-of-concept studies to be performed in the setting of an intact immune and
respiratory system. Animal models also provide initial safety and pharmaco-kinetic/dynamic data to
guide dose levels used in clinical studies. These models will be performed by industrial and
academic partners, and will be refined to reflect the severe asthma handprints derived from other
Work Packages.
WP6 have recently reviewed and critically assessed the existing animal in vivo models and their
predictive value in clinical development of novel asthma drugs. The most relevant model(s) have
been selected for validation with the most important measures being those that can be directly
related to patient samples e.g. BAL mediators and lung function. Previous and novel ‘fingerprints’ of
inflammatory parameters and airway physiological data available from EFPIA members in
conjunction with that from Academic groups will be analysed to define the optimal in vivo animal
models. These fingerprints will be kept and compared with those obtained from patients with severe
asthma when data becomes available during 2013.
To further these goals we have developed the following specific aims:
1. To examine novel aspects of the murine FCA model of severe asthma and assess whether
this will allow therapeutic pharmacological intervention
2. To determine effect of inhibition of other pathways implicated in chronic HDM model of
asthma including, but not restricted to, anti-IL-5, anti-IL-13, p38 MAPK and NOS2 inhibition
3. To compare ‘paw-print’ of inflammatory and AHR profile with that observed with chronic
HDM model and with clinical observations and ‘omics profiles in human severe asthma using
data analysis packages through eTRIKs
4. To examine the effect of acute and/or chronic ozone challenge on inflammatory and AHR
parameters i.e. can the model be exacerbated?
5. Work in close collaboration with other researchers using ex vivo human challenge models to
mimic effects in isolated murine epithelial and ASM cells
The following readouts will be used: (i) BAL cytokine/chemokine expression and absolute and
differential cell counts, (ii) MSD/Luminex and FACs/Cytospin analysis, (iii) tissue cytokine and
chemokine expression, (iv) tissue T-cell subsets – FACs analysis, (v) immunoglobulin typing, (vi)
lung/airway histology, (vii) lung function measured by respiratory mechanics including pulmonary
resistance or FOT/reactance and plesthmythography, (viii) IgE and allergen-specific IgE levels and
(ix) prepare and store samples for future transcriptomic analysis.
Job Summary
You will be responsible for carrying out the studies described above. In addition to this, you will be
responsible for the maintenance and care of laboratory instruments you will be using, and will be
expected to learn and apply any new techniques needed for successful completion of the study.
You will be expected to supervise others involved in this work e.g. Research Technician or
postgraduate students. You will also be expected to analyse the data acquired and to present data
to the Research group on a regular basis and to departmental meetings.
As part of the UBIOPRED Consortia, you will be expected to collaborate closely with the other
centres involved in WP6 and other WPs within UBIOPRED. This may involve travelling to these
centres and doing some experiments at those localities. Additionally, you will take part in regular
face-to-Face and Telephone conferences, and will be expected to submit publications to refereed
journals and to write reports for the supervisor and for the IMI.
Research Duties
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To conduct and plan own scientific work with appropriate supervision
To maintain highly organised and accurate record of all experimental work
To conduct data analysis, ensuring the validity and reliability of data at all times
To familiarise with any new techniques needed for project
Willingness to work out of normal working hours (including weekends) if the requirements of the
project demand
To write reports for submission to research sponsors
To contribute to the smooth running of the Group’s laboratories and, facilities with other
scientists, clinicians, technicians and students within the laboratories
To participate in Group research meetings and internal seminars
To participate in Consortia Face-to-Face and TC meetings
To collaborate with other allied scientists within Imperial College, the UBIOPED Consortia and
abroad, as appropriate
To publish in high quality journals and to present data at national and international meetings
Assist in the supervision of undergraduate and postgraduate research Students, research
assistants and Clinical Research Fellow as required
Other Responsibilities
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To undertake appropriate administrative tasks
To undertake any necessary training and/or development
Any other duties commensurate with the grade of the post as directed by line manager as well
as Head of Section
To observe and comply with all College policies and regulations, including the key policies
and procedures on Confidentiality, Conflict of Interest, Data Protection, Equal Opportunities,
Financial Regulations, Health and Safety, Imperial Expectations (for new leaders, managers
and supervisors), Information Technology, Private Engagements and Register of Interests,
and Smoking.
To undertake specific safety responsibilities relevant to individual roles, as set out on the
College
Website
Health
and
Safety
Structure
and
Responsibilities
page
(http://www3.imperial.ac.uk/safety/policies/organisationandarrangements).
Job descriptions cannot be exhaustive and the post-holder may be required to undertake
other duties, which are broadly in line with the above key responsibilities.
Imperial College is committed to equality of opportunity and to eliminating discrimination. All
employees are expected to adhere to the principles set out in its Equal Opportunities in
Employment Policy, Promoting Race Equality Policy and all other relevant guidance/practice
frameworks.
IMPERIAL COLLEGE LONDON
PERSON SPECIFICATION
Qualifications
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PhD in Biological Sciences, or a closely related discipline, or equivalent research in a
Pharmaceutical environment
Current Home Office Licence for Animal experimentation
Knowledge / Experience
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Practical experience in animal models of asthma
Knowledge of airway inflammation
Knowledge of peripheral biomarker models of pulmonary inflammation
Familiarity in handling mice, lung physiology and collection of tissues
Practical experience within a research environment and/or publication in refereed journals
Experience with intra-tracheal administration of substances would be advantageous
Experience in working independently within a team to ensure a defined outcome which
incorporates external data
Knowledge of research methods and statistical procedures
Computer literate with a good knowledge of different computer programs with experience in
data presentation and statistical analyses
Knowledge and use of computer-based in vivo data capture systems such as IDBS
eWorkbooks
Skills and Abilities
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Ability to organise own work with minimal supervision
Ability to prioritise own work in response to deadlines
Advanced computer skills, including word-processing, spreadsheets and eWorkbook
Ability to produce a high standard of work working to Industry-style guidelines
Creative approach to problem-solving
Excellent verbal communication skills and the ability to deal with a wide range of people
Excellent written communication skills and the ability to write clearly and succinctly for
publication
Personal Attributes
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Willingness to work as part of a team and to be open-minded and cooperative
Flexible attitude towards work
Discipline and regard for confidentiality and security at all times
Willingness to undertake any necessary training for the role
Willingness to travel both within the United Kingdom and abroad to conduct research and
attend conferences