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Respiratory Research Group
Research Associate
(Ref: MHS/11514)
• The University invites applications for the above post which is tenable to 30 November 2013 • Salary will be within the range £28,983 - £34,607 per annum according to relevant experience. . • Informal enquiries may be made to Dr Richard Booton, Clinical Senior Lecturer in Respiratory Medicine, University Hospital of South Manchester • If you wish to be considered for this post you should contact your HR team supplying a copy of your WITH THE COMPLIMENTS OF THE DIRECTORATE OF HUMAN RESOURCES
School of Translational Medicine, University Of Manchester,
& AstraZeneca UK Ltd

Job Title:

Organisation Unit: School of Translational Medicine, Faculty of Medical and Human Sciences
Early Disease Group (University Hospital of South Manchester), Respiratory Research Group (Stopford Building, University of Manchester) and AstraZeneca Pharmaceutics (Alderley Park, Cheshire)
Project Outline

Lung cancer is the most common cause of cancer related death accounting for approximately 28%
or 160,000 deaths in the USA in 2009. Non-small cell lung cancer (NSCLC) which is primarily
composed of adenocarcinoma and squamous cell carcinoma is responsible for 80% of lung cancers.
In the UK, fewer than 15% of patients present with early stage disease where cure is possible.
Understanding the biological behaviour of this lethal disease will facilitate rationale approaches to
early detection and adjuvant treatment strategies that may impact upon disease mortality in the near
Non-small cell lung cancer detection in at-risk populations, adjuvant treatment of resected disease or
treatment of relapsed disease, requires the development of robust biomarkers and the identification
of novel therapeutic targets. This is a difficult area of work in NSCLC given the relative scarcity of
cancer tissue at diagnosis and the absolute lack of cancer tissue from recurrent disease.
Understanding the processes that drive cancer initiation, from pre-neoplastic to invasive disease,
and that force some cancers to recur after an apparent complete resection, will aid our
understanding of the natural history of this common fatal disease, and provide insights into potential
targets that may help to screen-detect relevant cancers and to stratify and direct effective advances
in adjuvant therapy.
To address this question, the University of Manchester and AstraZeneca UK have together provided
an outstanding opportunity for a Post-Doctoral Research Associate in the Functional Genomics of
NSCLC. The project will use advanced genomics techniques including next generation sequencing,
combined with bioinformatics to measure the levels of protein coding and non-coding RNAs in
biopsies obtained from patients with recurrent lung cancer. This will result in the identification of
potential novel biomarkers and therapeutic targets that can be employed to drive adjuvant therapy in
non-small cell lung cancer (NSCLC). The validity of these targets will be tested using a variety of
molecular, biochemical and cell biology techniques including RNA interference, plasmid/viral-
mediated over-expression and laser capture microscopy.
The post holder will spend time within:
Early Disease Group (EDG) at the North West Lung Centre, University Hospital of South Manchester Respiratory Research Group at the Stopford Building (University of Manchester) AstraZeneca Genomics Facility, Alderley Park, Cheshire
Primary supervision will be provided Dr Richard Booton at the University Hospital of South
Manchester and will be supported by Dr Mark Lindsay (University of Manchester) and Dr David
Blowers/Dr Neil Gibson (AstraZeneca Pharmaceuticals).
Main duties and responsibilities

• after discussion with the above named supervisors, the post holder will design and execute agreed scientific projects, report back with their results and interpretation for further discussion and forward planning. • take an active role in discussion, design, optimisation, interpretation and validation of new • keep a watching brief on new technologies pertinent to the project • actively participate in EDG, respiratory research group and AstraZeneca group meetings on a • present their work at National and International meetings as appropriate. • will be responsible for preparing manuscripts of their work for publication in high quality peer
Person Specification
• Hold (or expect to hold shortly) a Ph.D. (or equivalent) in a relevant area of biology • Demonstrated experience in molecular and/or cellular biology • Publication record in peer reviewed journals • Have demonstrated ability to work both independently and as part of a team • Be able to develop and refine techniques and experimental approaches. • Previous experience in cancer biology • Experience in computing and bioinformatics
Background and Further Information
The University of Manchester
The University became the largest single site University in the UK in 2005 with the merger of the
Victoria University of Manchester and the University of Manchester Institute of Science and
Technology (UMIST).
School of Translational Medicine, Respiratory Research and the Early Disease Group

The School of Translational Medicine encompasses three research groups, Epithelial Sciences,
Musculoskeletal and Respiratory. The Respiratory Research Group, with facilities at the University
Hospital of South Manchester and the Stopford Building (central Manchester), employs about 50
staff and has an annual research income of approximately £14 million. It has 4 independent
research groups investigating the mechanisms of respiratory disease. The Early Disease Group
(EDG) was formed in July 2008 to develop a portfolio in lung cancer, and lies within the Respiratory
Division. The Group has grant income of ~£1M from the Charitable Moulton Foundation,
AstraZeneca Pharmaceuticals and UHSM Endowment Fund
Current Staff
Dr Richard Booton, Clinical Senior Lecturer in Respiratory Medicine & Oncology
Dr Philip Barber, Consultant Respiratory Physician
Mr Rajesh Shah, Consultant Thoracic Surgeon & Honorary Lecturer
Dr Paul Taylor, Consultant Medical Oncologist
Dr Yvonne Summers, Consultant Medical Oncologist
Sr Julie Martin, Nurse Bronchoscopist
Dr Philip Crosbie, NIHR Clinical Lecturer
Sr Christina Dale, Senior Research Nurse
Dr Louise Brown, Clinical Research Fellow
Dr Fauziah Nordin, Clinical Research fellow
Kate McCalman, Research Nurse
Research Fellow (this post)
The group has significant research links with the School of Cancer & Enabling Sciences (Prof
Whetton), the Lymphoma Group (Prof Radford), the Lung Focus Group at the Christie Hospital (Dr
Blackhall) and Dr Mark Lindsay (Reader in Biopharmaceutics). In particular, the Group works closely
with the Manchester Cancer Research Centre and has been pivotal to the successful development
of the MCRC Lung Cancer Tissue Biobank.
Current Projects:
1. A proteomic exploration of pulmonary blood in early stage NSCLC. 2. Exon array analysis of progressive bronchial dysplasia 3. Expression of long non-coding RNA in resected adenocarcinoma & squamous cell carcinoma 5. Development of Squamous Cell Carcinoma Tissue Microarray 6. Incidence, Prevalence, and Biology of Progressive Preneoplastic Bronchial Dysplasia in Two Distinct, Potential Screening Cohorts, of Patients At High Risk for Lung Cancer L Brown, P Barber, R Booton 7. An Integrative Genomic Exploration of Preinvasive and Recurrent NSCLC R Booton, N Gibson, M Lindsay, D Blowers (this project) 8. LungSEARCH. A randomised controlled trial of lung cancer screening in mild-moderate COPD Chief investigator S Spiro; Principal Investigator (Manchester) R Booton
AstraZeneca, Discovery Medicine Department, Alderley Park, Cheshire

Cancer R&D at Alderley Park has a proven track record of delivering an extensive range of world-leading projects and products. As the new range of targeted therapeutics move towards the clinic, we are placing an increased emphasis on understanding the links between the chosen molecular target, disease type/stage and drug responses. We aim to stimulate continued creativity throughout our organisation by encouraging a culture in which our people feel valued, energised and rewarded for their ideas and contribution to our success. And we support our people in discovering their own potential, through excellent learning and development opportunities that are available at every stage of an individual’s career. • Our powerful product portfolio includes many world leaders and a range of high-potential therapies for treating cancer (Casodex, Arimidex, Faslodex and Iressa), • We spend over $14 million every working day on research and development. (Total R&D spend • Corporate HQ in London UK, R&D HQ in Södertälje, Sweden and a strong presence in the key • We are active worldwide, with sales in over 100 countries, manufacturing in 20 and major • AstraZeneca has over 60,000 employees worldwide. Along with our commitment to competitiveness and performance, we continue to be led by our core values to achieve sustainable success: • Integrity and high ethical standards • Respect for the individual and diversity • Openness, honesty, trust and support for each other • Leadership by example at all levels
A key site in the AstraZeneca global network, our major facility at Alderley Park is home to some of
the world's most skilled industry professionals. The majority of the 4,500 people based in this
uniquely attractive parkland setting are dedicated to Research & Development. Covering 400 acres,
three-quarters of which remains woodland, water and farmland, Alderley Park is where several of the
world's most important medicines have been discovered and developed. The site is a combination of
historic green parkland and ultra modern high-tech steel and glass. A dynamic place to work, the site
and its employees make a strong contribution to the local community.
The Manchester Area

The City of Manchester has been subject to vast redevelopment in recent years and continues to
have ambitious plans for the future. The amenities and facilities offer a variety of City Life and
entertain a vibrant social and cultural scene. Four of the city’s impressive museums are among the
shortlist of national important museums. An impressive collection of paintings are on show at the
Manchester Art Gallery, and classical / musical concerts are enjoyed at four key venues
(Bridgewater Hall, GMEX Centre, Manchester Apollo & Manchester Evening News Arena). The
metro-tram has made a successful return and makes for a surprisingly quick journey across city and
routes now cover much of Greater Manchester.
The city has a sound reputation for sport and held the Commonwealth Games in 2000. Manchester
United Football Club, one of the most popular football clubs, is situated close to the city centre. For
those who are not football fans, Manchester offers superb city centre and out of town shopping facilities (Trafford Centre) and now has a Harvey Nichols and Selfridges’. For those who enjoy the countryside, Manchester is closely located to the Peak and Lake District, which boast some of England’s most breathtaking scenery. For further information on the area, please visit the websites below., PROJECT DESCRIPTION
1) The clinical fellow will join the EDG team and contribute to the recruitment and management of
the established longitudinal surveillance study, with a particular focus on patients undergoing curative resections for non-small cell lung cancer, and coordinate the recruitment of additional patients to facilitate image guided biopsy of recurrent disease. The fellow will focus specifically on establishing a collection of pathologically staged archival NSCLC tissues and their serial biopsies, and also organise the transfer of fresh frozen tissue from the MCRC Biobank, where available. The post holder will be responsible, with the assistance of research nurse support, for the collection of fresh and archival biopsy material from patients with recurrent disease. The post holder will establish a comprehensive clinicopathological database and help to develop the most effective strategy for genomic analysis, using either fresh tissue or formalin fixed paraffin embedded samples. As well as the intellectual challenge that involves comprehending the relationship between the biology of pre-invasive disease, primary tumour, and metastases, technological challenges remain and will be tackled by the clinical fellow, including the validation of archival FFPE material for use in next generation sequencing, the use of laser microdissected samples and bioinformatic analysis. The planned molecular profiling of the study samples includes transcriptome and genetic profiling using next-generation sequencing (NGS). The successful candidate will be responsible for undertaking the appropriate analyses in order to determine the molecular determinants of early stage lung cancer. This will include: - Working with biostatisticians and informaticians to analyse, mine, and view the data. - Designing and performing analyses to identify transcript profiles of disease and disease progression and also the identification of key somatic mutations and gene fusions. - Integrating and comparing analysis results with internal and external biomarker-relevant data repositories, such as clinical, genetic, phenotypic, proteomic, genomic, and transcriptome datasets. - Identifying key pathways relevant to disease initiation and progression. - Identifying biomarkers for risk of recurrence, patient stratification etc. In addition to the challenges posed by molecular characterisation, the clinical fellow will initiate and
perform the clinical studies summarised below.
Testable Hypotheses in Non-Small Cell Lung Cancer
1. Structural genomic abnormalities (single nucleotide polymorphisms, somatic mutation, gene a) Preinvasive and invasive lung cancer morphologies (CIS vs. squamous) b) Different lung cancer morphologies (squamous vs. adeno vs. large cell) c) Primary & recurrent NSCLC tissues d) Primary tissues that do and do not recur 2. Functional genomic abnormalities (gene expression, splice variation, expressed SNP’s, non- coding RNA species) are different in a) Preinvasive and invasive lung cancer morphologies (CIS/ AAH vs. squamous/ adeno) b) Different lung cancer morphologies (squamous vs. adeno vs. large cell) c) Primary & recurrent NSCLC tissues d) Primary tissues that do and do not recur 3. Presence of putative structural/ functional genomic candidates predicts for progression to 4. Genomic candidates can be detected in peripheral blood


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