AMMF Funded Project: An integrated analysis of proteomics and metabolomics in cholangiocarcinoma to identify pathways for target development programme

Cholangiocarcinoma is one of the most common malignancies in primary liver cancer. The majority of these tumours are inoperable and resistant to conventional chemotherapy. There is an urgent need to identify their molecular mechanisms for development of targeted therapy in the future.

Prevailing theories suggest that primary cholangiocarcinoma formation is potentiated by mutated cholangiocytes in human bile ducts. These cells exhibit some unique characteristics and reorganize metabolism to fuel malignant growth and invasion. Since their genetic alterations lead to aberrant protein expression and metabolic activity, an integrative analysis of proteomics and metabolomics data will be a powerful approach helping to identify some important oncogenic pathways and oncometabolites for cholangiocarcinoma; and correlation of them with clinicopathology will support target development for novel therapy.

This project will provide an opportunity for a student to work with us to: (1) make of use of integration analysis across proteomics and metabolomics to identify pathways in common; (2) evaluate the pathways in models of cell cultures and animal experiments including using the CRISPR/Cas9 genome editing; and (3) access to clinical samples for immunohistochemical staining and correlate them with clinicopathology of cholangiocarcinoma for prognostic evaluation.

A DPhil candidate working on this project would be jointly supervised by Dr Shijie Cai and Professor David Kerr. The candidate will write reports to the funding body periodically and be based in the John Radcliffe Hospital at Nuffield Division of Clinical Laboratory Sciences.

This project is funded by the Alan Morement Memorial Fund (AMMF) The Cholangiocarcinoma Charity.

TRAINING OPPORTUNITIES

The student will acquire expertise in a wide range of state-of-the-art molecular and cell biological techniques, and bioinformatics analysis; consequently providing an excellent foundation for a research career. Formalised training and assessment of each technique either by Dr Cai or other members of the laboratory as appropriate. Our laboratory has clearly defined protocols to support training in specific experimental techniques. Standard operating procedures are regularly updated to ensure that methods are optimal.

As well as the specific training detailed above, students will have access to a wide-range of seminars and training opportunities through the many research institutes and centres based in Oxford. Students are also able to attend the Methods and Techniques course run by the MRC Weatherall Institute of Molecular Medicine. This course runs through the year, ensuring that students have the opportunity to build a broad-based understanding of differing research techniques.

Generic skills training is offered through the Medical Sciences Division’s Skills Training Programme. This programme offers a comprehensive range of courses covering many important areas of researcher development: knowledge and intellectual abilities, personal effectiveness, research governance and organisation, and engagement, influence and impact. Students are actively encouraged to take advantage of the training opportunities available to them.

The Department has a successful mentoring scheme, open to graduate students, which provides an additional possible channel for personal and professional development outside the regular supervisory framework. We hold an Athena SWAN Silver Award in recognition of our efforts to support the careers of female students and staff.