Clinical Surgery

Jobs

Posts within Clinical Surgery are advertised primarily through the British Medical Journal.

The following projects are currently available for individuals considering applying for Spire Murrayfield Resident Medical Officer Fellowships. Please contact Murray.Britton@ed.ac.uk for advice on Spire fellowship recruitment. Specific advice on projects can be obtained from supervisors listed below.  Please note these projects may also be available to individuals applying for funding from other funding councils. 

Resident Medical Officer
Reports to: Head of Clinical Services (HOCs) and through HOCs to Medical Advisory Committee Chair
Job Purpose: To be part of a team providing 24 hour medical cover for all routine medical care and response to consultant requests. Immediate first line resuscitation to patients, visitors or staff member as required.
To assist in the management of patients and provide back-up support to consultant.
Please see PDF below for the full job description.
Resolution of organ injury after acute pancreatitis (RESORP Study)
Supervisor: Mr Damian Mole (MRC Senior Clinical Fellow, Centre for Inflammation Research, University of Edinburgh). 
Contact: damian.mole@ed.ac.uk

Description: Even after an apparent complete clinical recovery from an episode of critical illness – for which severe acute pancreatitis (AP) is a paradigm - life expectancy is reduced. The legacy of AP on individual organ function in humans is not known. This project, funded by an MRC Senior Clinical Fellowship to the supervisor, will define the pathophysiological impact of AP on organ-specific function by conducting an in-depth assessment of patients’ health at presentation, and at 3 months and 27 months after the first episode of AP using markers of organ function and/or disease in the peripheral blood. A nested cohort will undergo in-depth organ-specific evaluation of cardiovascular, respiratory, pancreatic (exocrine and endocrine), immunological, and cognitive function, coupled with multi-parameter MRI imaging to define hepatic and pancreatic fibrosis. Biological indices of senescence in the context of human organ performance will be measured. This project will be attractive to an individual with enthusiasm for translational medicine, physiology, molecular science, and clinical trials. A well-resourced laboratory-based research programme runs in parallel to this clinical study, and the individual engaged in this project will have ample opportunity to engage in cutting-edge molecular translational science. The fullest support would be given to a talented individual who wished to extend their participation in the project by capitalizing on the cohort data and sample streams, through a personal Clinical Training Fellowship application to e.g. the MRC or Wellcome Trust.

Liquid biopsy for early detection of pancreas and liver cancer.
Supervisors: Mr Damian Mole (MRC Senior Clinical Fellow, Centre for Inflammation Research, University of Edinburgh), Dr Nizar Batada (Chancellor's Fellow, Institute of Genetics and Molecular Medicine, University of Edinburgh) Prof Tim Aitman, Professor of Molecular Pathology and Genetics, Institute of Genetics and Molecular Medicine, University of Edinburgh).
Contact: damian.mole@ed.ac.uk

Description: Rapid advances in the early detection of solid tumours are being made through the application of high throughput -omics approaches to the analysis of peripheral blood samples ­– the liquid biopsy. Circulating cell-free DNA in peripheral blood and inflammatory white blood cell phenotyping offer two complementary approaches to early detection of tumours and rapid precision diagnosis. This project will be attractive to an individual who wants to develop knowledge and skills in liquid biopsy theory and practical applications. They will assume responsibility for the coordination of recruitment and blood/tissue sampling of patients undergoing surgery for liver and pancreas cancer, including operating theatre samples, and will work closely with teams at the IGMM to develop state of the art liquid biopsy technology for this important medical need. The fullest support would be given to a talented individual who wished to extend their participation in the project through a personal Clinical Training Fellowship application to the MRC, Wellcome Trust or CRUK, if they so wished.

3D-bioprinted models to accelerate and enhance the treatment of pancreas cancer.
Supervisors: Prof Nick Leslie (Professor and Deputy Head of Institute, Institute of Biological Chemistry, Biophysics and Bioengineering, Heriot Watt University) and Mr Damian Mole (MRC Senior Clinical Fellow, Centre for Inflammation Research, University of Edinburgh).
Contact: damian.mole@ed.ac.uk

Description: We have developed a new and widely-applicable 3D printing technique which we are using to print pancreatic cancer cells mixed with other the normal cells and protective proteins which are found in pancreas tumours. In the long term, we believe that this will be able to recreate tumour-like constructs which should give much closer models of human cancer to accelerate and enhance drug development, answer important questions in tumour biology, and streamline precision medicine by having unique control in experiments over the 3D distribution of different cells and other components within printed tumours. This project will be attractive to an individual who wants to be at the forefront of technology development in this area. The individual will assume responsibility for the coordination of recruitment and blood/tissue sampling of patients undergoing surgery for pancreas cancer, including operating theatre samples, and will work closely with bioengineering teams at Heriot Watt University to develop this exciting technology for this unmet medical need. The fullest support would be given to a talented individual who wished to extend their participation in the project through a personal Clinical Training Fellowship application to the MRC, EPSRC, BBSRC (now UKRI), Wellcome Trust or CRUK, if they so wished.

Machine learning approaches to ultrasound signal processing to enhance the diagnosis of liver tumours.
Supervisors: Dr James Hopgood (Senior Lecturer in the Institute for Digital Communications, School of Engineering, University of Edinburgh) and Mr Damian Mole (MRC Senior Clinical Fellow, Centre for Inflammation Research, University of Edinburgh).
Contact: damian.mole@ed.ac.uk

Description: Ultrasound is an excellent tool for imaging the liver. However, contrast enhanced CT scan and contrast enhanced MRI remain the gold-standard techniques because of their ability to discriminate between different liver pathologies. The aim of this project is to use machine learning techniques to enhance the signal processing of digital images obtained at ultrasound, thus increasing the accuracy of diagnosis of liver lesions, and eliminating or reducing image background noise. This project works closely with signal processing experts in the School of Engineering, University of Edinburgh to apply machine learning principles to extract hidden rules, relations, hierarchy, correlation and other hidden knowledge within a set of ultrasound data images. The individual choosing this project could come from a wide background and have an interest in hepatology, liver surgery (including transplant), radiology or surgical technology and informatics. They would assume responsibility for recruitment and arranging (and performing, if they wished to learn) ultrasound scans in patients with suspected liver pathology, and work closely with existing team members to develop exciting new signal processing technology. The fullest support would be given to a talented individual who wished to extend their participation in the project through a personal Clinical Training Fellowship application to the MRC, Wellcome Trust or CRUK, or joint funding with EPSRC/BBSRC (now UKRI), if they so wished.

Exploring the use of qFIT as part of the assessment of lower GI symptoms: The impact of genetic effects on cancer risk and bleeding tendency.
Proposed Supervisor: Professor MG Dunlop, Academic Coloproctology, Institute of Genetics and Molecular Medicine and Edinburgh Colorectal Surgery, Western General Hospital, Edinburgh.
Contact: malcolm.dunlop@ed.ac.uk

Quantitative faecal immunological testing (qFIT) for human haemoglobin in the stool has been rolled out in Scotland as a screening test for population bowel cancer screening. Similarly, it is soon to be rolled out in England as a screening test, albeit at a higher qFIT threshold and older age-group than in Scotland. The test performance metrics have been established for screening the general population, the thresholds of 80ug/g has been applied in Scotland, whilst in England a threshold level of 140ug/G is being mooted.  There is a critical balance between qFIT test sensitivity and specificity, which directly impacts on demand and capacity of downstream clinical investigation – namely colonoscopy.

Led by Professor Dunlop and Miss FVN Din, qFIT is being rolled out (1st May 2018) for all symptomatic referrals within Lothian - in parallel with colonoscopy (or CT colonography). This will allow gold standard assessment of qFIT test performance at various thresholds. Assessment of qFIT levels will be conducted in 18,000 patients (6000 referrals annually) without influencing clinical decision-making by including information on stool hHb level as assessed by qFIT. This approach has never been carried out in such a large population and so offers unique opportunity for research with implications likely to have direct impact on health outcomes. This fellowship aims to explore the capacity and caseload demand on colonoscopy services by modelling different thresholds, with the ultimate aim of incorporating patient-specific threshold levels dependent on overall prediction of significant pathology. Varying qFIT thresholds will be assessed using risk models developed to include demographics, symptoms, screening history, family history and genetics SNP marker data. This will be the main focus of the planned fellowship. Ethical approvals are already in place to recruit patients attending secondary care for genetic testing linked with all of the above variables. A specific focus of the proposed short term fellowship will be to study the impact of bleeding tendencies in symptomatic people who attend with positive (and negative) qFIT tests at various thresholds. Quantitative assessment of coagulation cascades – in particular von willebrand factor - will be conducted and genomewide genotyping arrays will be run on all recruits to enable genetic prediction of coagulation and bleeding tendencies in the tested population using mendelian randomisation. There are already over 70 common genetic variants shown to impact on vwf levels and this approach will be the first to directly assess the impact of these genetic variants on bleeding in the gut, as measured by qFIT. This is a completely untapped area of research that will be unique to the proposed fellowship, with the aim of generating pilot data and expertise that could lead to successful funding application for a research fellowship to MRC or CRUK.

The Colon Cancer Genetics Groups have excellent laboratory facilities and all the necessary expertise to explore epidemiology and conduct genetic association studies at scale, as well as translate the results to meaningful clinical endpoints. The successful candidate will gain training and exposure to clinical and translational research approaches, genetics, statistics and statistical genetics and will be part of a vibrant research environment in the CCGG which has a broad mix of scientific, clinical academics, technicians and PhD students all research-focused on combating colorectal cancer for early detection and prevention.

Relevant background references

  • Van Loon et al. Genome-wide association studies identify genetic loci for low von Willebrand factor levels. Eur J Hum Genet 2016; 24:1035-40.
  • Smith NL et al.  Novel associations of multiple genetic loci with plasma levels of factor VII, factor VIII, and von Willebrand factor: The CHARGE (Cohorts for Heart and Aging Research in Genome Epidemiology) Consortium. Circulation 2010; 121:1382-92.
  • Quyn et al. Application of NICE guideline NG12 to the initial assessment of patients with lower gastrointestinal symptoms: not FIT for purpose? Ann Clin Biochem 2018;55: 69-76.
  • Zheng J et al. Recent Developments in Mendelian Randomization Studies. Curr Epidemiol Rep 2017; 4:330-345.
Investigating the ability of chemopreventive agents to rescue abnormal neoplasia-prone phenoytpes in ex-vivo human colonic organoid models.
Supervisors: Miss Farhat Din, Senior Lecturer & Honorary Consultant Surgeon; Dr Asta Valanciute, Post-doctoral scientist, MRC Institute of Genetics & Molecular Medicine. 
Contact: farhat.din@ed.ac.uk

Background: Colorectal cancer (CRC) is preventable. There is compelling rationale to capitalise on known preventative agents to define mechanisms underlying CRC risk and mode of prevention. Understanding aetiology underpins prevention strategies. Environmental exposure accounts for 50-60% of variance in CRC risk. CRC risk factors, diabetes, obesity, and metabolic syndrome, highlight links with metabolism. Energy imbalance, driven by environment and genetics, alters stem cell metabolism rendering it vulnerable to CRC. Nutrient flux determines cellular outcome. Stem cells maintain homeostasis in response to intrinsic genetic variation and environmental stimuli. Nutritional overload increases ‘stemness’, self-renewal or differentiation ability, in intestinal crypts. The project is founded on the hypothesis that aberrant cancer metabolism perturbs intestinal stem cell homeostasis and chemopreventive agents counter the effects of excess nutrients on stem cell behaviour to modify neoplastic phenotypes.

Project outline: Human colonic organoids from normal mucosa and adenoma tissue from familial adenomatous polyposis patients and non-genetically predisposed patients will be exposed to chemopreventive agents (aspirin, metformin, other). Both phenotypic changes such as rescue of the abnormal Wnt-driven cystic phenotype and changes in stem signalling related RNA transcripts (RNA-Seq). This translational project will provide and ideal opportunity to undertake both wet-lab work with novel techniques such as human organoid culture and bioinformatics analysis- providing a broad base of skills to take forth to doctoral research.  All experiments will be clearly outlined and supervised to allow progression of the project. This project is an exciting opportunity to undertake colorectal cancer research in a well- established translational lab with a track-record of supervising clinical fellows and mentoring research careers.

Identifying the specific mRNA target in chemopreventive intervention study in humans. 
Supervisors: Miss Farhat Din, Senior Lecturer & Honorary Consultant Surgeon; Dr Asta Valanciute, Post-doctoral scientist, MRC Institute of Genetics & Molecular Medicine. 
Contact: farhat.din@ed.ac.uk

Background: Substantial evidence indicates aberrant metabolic signalling underlies colorectal cancer (CRC) carcinogenesis. mTOR signalling, key to metabolism, regulates protein translation and growth. Cancers, due to high metabolic demands, exploit mTOR signalling to increase protein translation. mTOR _ENREF_4is upregulated in adenomas and CRCs. The host lab has shown that aspirin and metformin inhibit mTOR signalling in colorectal cancer2 and inhibits protein translation. Classical mTOR inhibitors such rapamycin preferentially regulate a specific type of MRNA but do not impart the same magnitude of cancer protection as aspirin. It is important to determine whether these chemopreventive agents preferentially inhibit specific mRNAs in humans.

Project outline: Blood and normal rectal mucosa will be sampled before and after the chemopreventive agent in this translational drug intervention study. Pre- and post-exposure normal rectal mucosa and blood will undergo transcriptome (RNA-seq) and metabolic profiling. This project will provide an excellent training opportunity to undertake clinical translational research encompassing patient recruitment, sample harvest, RNA extraction and analysis providing a broad skill-set to take forth to doctoral research.  All experiments will be clearly outlined and supervised to allow progression of the project. This project is an exciting opportunity to undertake colorectal cancer research in a well- established translational lab with a track-record of supervising clinical fellows and mentoring research careers.  

Clinical positions

Clinical positions within the department are generally advertised nationally through the British Medical Journal Careers section.

Other positions

Details of University of Edinburgh positions are also available from the University recruitment website.