Oncogene-induced reprogramming of heterotypic cellular interactions

The accumulation of mutations during the development of cancer subverts normal cell-to-cell communication and cellular decisions. Deciphering the mechanisms that underlie cell decisions such as fate determination, cell cycle regulation and cellular migration is critical not only to identifying the molecular determinants of disease but also to the development of future cancer therapies. In particular, our understanding of the role and mechanisms of heterotypic cellular interactions during oncogenesis and therapy is severely lacking, hampered by methodological challenges associated with monitoring cell-to-cell communication between individual cells over time.
Dr Alessandro Esposito and his team have established techniques to enable live imaging of biochemical activities with subcellular resolution, light-inducible control of enzymatic activities, tracking and modelling of cellular populations. We are applying these unique tools to the study of how oncogenic KRAS mutations alter cell signalling and metabolism, and cellular phenotypes during early oncogenesis. Dr Jacqueline Shields and her team investigate how the “normal cells” of the tumour microenvironment - the stroma - regulate immune activity from early stages of disease to promote carcinogenesis. To do this, we examine both the primary tumour and draining lymph nodes developing complex culture systems and organ-on-a-chip models to monitor heterotypic cell interactions with low invasiveness.

This project will exploit these novel technologies to understand how oncogenic KRAS mutations alter cell-to-cell interactions between wild-type and mutant cells or between mutant cells and stroma contributing to the deregulation of tissue homeostasis during early oncogenesis. The project will offer a unique opportunity to train across disciplines through a strong partnership between groups specializing in oncology, engineering and biophysics.

More information about the research undertaken in the Esposito and Shields groups can be found here: https://quantitative-biology.org
www.mrc-cu.cam.ac.uk/research/Jacqui-Shields-folder

Applications will need to be made through the University Application Portal and will entail an application fee of £65. Please visit: www.graduate.study.cam.ac.uk/courses/directory/cvcupdmsc/apply for further information about the programme and to access the Applicant Portal. Please note that the course code for PhD applications to the MRC Cancer Unit is MDCU22. Whilst making your online application please make it clear which project area(s) and principal investigator(s) you are interested in working with. Your online application needs to include:
• A CV, including full details of all University course grades to date.
• Contact details for two academic or professional referees.
• A personal statement outlining your interest in a specific project area, what you hope to achieve from a PhD, and your research experience to date.

The above information must be provided under relevant sections on the application portal.

Completing the Research section
If you are applying for one project only: in the ‘Proposed title of Research’ textbox, insert the project title. If you wish to apply for more than one project, insert ‘Cancer Research’.

If you are applying to more than one supervisor: in the ‘Proposed Supervisor’ textbox, insert the initials of the Supervisors you wish to consider your application and in the ‘Research Summary’ textbox, insert the project titles being offered by those Supervisors.

Please describe your research experience in the appropriate textbox.

Interviews are expected to take place in December.

Please contact [Email Address Removed] with any other enquiries concerning studentships or eligibility criteria.