• PhD Projects for 2019
 

Training - PhD Projects for 2019


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Applications for the projects below are now open, and close on Sunday 26 May

To join us as a Clinical Research Training Fellow, you will be a post-registration clinician, ideally with a specialist training post. You will receive running expenses, an appropriate salary and full coverage of university tuition fees.

A first or an upper second honours degree or the overseas equivalent will be vital for Non-Clinical Studentships. Your award will include running costs, tuition fees and a generous annual stipend.

Please see here for full instructions on how to apply.

 

1) Developing ex vivo models for breast cancer - understanding the link between tissue mechanics, genetic instability and cancer initiation.

  • Lead supervisor: Dr Andrew Gilmore
  • Co-supervisors: Dr Robert Clarke, Dr Sacha Howell

Breast cancer is the most common form of cancer in women, with over 54,000 new cases each year in the UK, and over 11,500 of these women die. In order to reduce these numbers, the causes of breast cancer need to be understood, and why some women are at a higher risk of developing the disease in the first place. Mammographic breast density (MBD) is the amount of a woman’s breast tissue that appears radio opaque in a mammogram. Data over a number of decades has shown that women with significantly higher MBD are 4-6 times more likely to develop the disease than women with low MBD. After age, this represents the highest independent risk factor, but the biological basis for the increased risk is unknown. Recent studies have shown that regions of high MBD are where the connective extracellular matrix (ECM) supporting and surrounding the epithelial ducts contains collagen that is more cross-linked and mechanically stiffer. These findings suggest that altered tissue mechanics might contribute to increased breast cancer risk.

The mechanical properties of tissues are important determinants of cell function. Tissues have defined mechanical properties, which cells interpret, and changes in these properties are linked to disease. Preliminary data using mammary epithelial cell lines has shown that increased stiffness of their ECM induces changes in gene expression such that these cells are less like epithelia and acquire genomic instability leading to transformation. This project will study this mechanism in primary human cells, using 3D ex vivo models where we can examine how changes in the ECM mechanics alter cell behaviour that contribute to cancer initiation. This project will work within both the Manchester Cancer Research Centre and the Wellcome Trust Centre for Cell/Matrix Research to develop the ex vivo models.

 

2) Neural information extraction for literature-based discovery of cancer mechanisms

  • Lead supervisor: Professor Sophia Ananiadou
  • Co-supervisors: Professor Niels Peek, Professor Andrew Renehan

The PhD will advance NLP research related with the automated extraction of cancer mechanisms from text by focussing on the identification of events, i.e., those involving entities that could explain interrelated phenomena occurring at various levels of biological organisation (e.g., molecule, cell, tissue, organ, organism), and the context under which they were observed. Event extraction will be based on novel deep learning techniques using joint training and multi-task learning. Contextual information of the extracted mechanisms will be quantitatively assessed based on the analysis of the language used to describe them. This information will support literature-based discovery for cancer mechanisms by inferring and ranking complex associations in context, and by combining results from text mining and omics data. Validation of the text mining methods will be conducted by replicating existing cancer associations. The proposed research will also facilitate signalling pathway reconstructions through the development of advanced text mining that will offer a paradigm shift in cancer model development, making the synthesis of information about cancer mechanisms from the literature more accurate and manageable.

 

3) Personalising TYA cancer follow-up through the capture of electronic Patient Reported Outcome Measures (ePROM)

  • Lead supervisor: Professor Janelle Yorke
  • Co-supervisors: Dr Martin McCabe, Professor John Ainsworth

Around 2,200 15 to 24-year-olds are diagnosed with cancer every year in the UK; this age group is referred to as ‘teenage and young adult’ (TYA). Survival from TYA cancer is improving. More than 80% of TYAs diagnosed with cancer in the UK now survive for at least five years; although there is considerable variation between the different diagnostic groups. With many TYAs surviving beyond five years late effects relating to the cancer site and/or cancer treatments have become increasingly apparent. Psychosocial and quality of life (QOL) impairments are also known to affect TYA cancer survivors. Late effect symptoms and QOL can be collected through the use of electronic patient reported outcome measures (ePROMs). The collection and use of remote monitoring ePROMs has been reported to show clinical benefit, including improved QOL and survival for adult cancer patients. However, routine ePROMs are yet to be developed and tested in TYA cancer patients.

The project will involve systematically reviewing and meta-synthesis of i) the qualitative literature of the experience of TYA cancer survivors and ii) published PROMs specific to cancer TYA. That work will inform the qualitative interviews with TYA cancer patients to develop a specific suite of fit-for-purpose ePROMs for follow-up monitoring of treatment related toxicities and QOL. The project will conclude with a pilot study of the electronic platform and collection of ePROM data for TYA cancer patients.

The studentship is funded through the new Christie Clinical Academic Pathway (CCAP) for nurse and allied health professionals. The project will be supervised by Professor Janelle Yorke (Chair Christie Patient Centred Research; Chair Christie ePROM group), Prof Ainsworth (Director Centre for Health Informatics), Dr Van Der Veer (ePROMs expert) and Dr McCabe (TYA medical consultant). Prof Yorke is an international leader in the development and validation of PROMs across a range of chronic conditions. Prof Ainsworth and Dr Van Der Veer will provide expertise in literature reviewing and ePROM platform development and pilot testing. Dr McCabe will provide expert medical input in the development and confirmation of PROMs with clinical and research utility.

Please note this project is aimed at and open to Nursing and Allied Health Professional (AHP) applicants only.

 

4) Geographical management of advanced breast cancer health disparities

  • Lead supervisor: Professor Janelle Yorke
  • Co-supervisors: Professor Andrew Wardley, Professor David French

There are more than 55,000 new cases of breast cancer in the UK each year, and approximately 78% of female patients survive 10-years or more. While Greater Manchester’s (GM) survival rates compare well nationally, there is significant disparity in survival depending on where in GM patients live. Such disparities result from a combination of modifiable social and health system determinants, including limited access to care, health literacy, financial resources, and structural barriers within the health system itself. As treatment options become more advanced and prognosis continues to improve surveillance of disparity in breast cancer care will become increasingly important to consider in understanding variation in outcomes and to develop effective interventions that reach all patients residing in GM. Identifying factors that contribute to persistent disparities can help to focus efforts to equalise health care access across geographically diverse populations.

The project will involve systematically reviewing and meta-synthesis of the qualitative literature of the experience of advanced breast cancer patients residing in geographically diverse populations. The review will inform the qualitative interviews with breast cancer patients at key points along the advanced breast cancer treatment pathway and interviews with clinicians providing care at different geographical locations. The Christie ePROM platform will be used to remotely monitor quality of life and patient experience and data interrogation at the patient level across different geographical areas. That work will inform the development and pilot testing of a service level intervention to safeguard standardisation of advanced breast cancer care and access to clinical trials across GM.

The studentship is funded through the new Christie Clinical Academic Pathway (CCAP) for nurse and allied health professionals. The project will be supervised by Professor Janelle Yorke (Chair Christie Patient Centred Research) and Professor Andrew Wardley (Consultant in Breast Medical Oncology). Prof Yorke has expertise in mixed methods studies and the development of complex interventions. Prof Wardley will provide expert medical advice on pathways and cancer treatment and service delivery.

Please note this project is aimed at and open to Nursing and Allied Health Professional (AHP) applicants only.