Deadline: 11 November 2013
Our training programme aims to develop a cohort of scientists equipped both intellectually and technically to conduct the highest quality research on cancer.
Our research degrees are supplemented by a comprehensive support programme, providing training in a wide range of biomedical laboratory methods and other vital transferable skills.
We are now inviting applications for the following research projects:
(Please click ont the project titles to jump to the project summary)
How to apply
Please send a covering letter and a copy of your cv to the supervisor you are interested in working with.
Characterization of the mechanism of IKK-i (inducible IKK or IKK-epsilon) oncogenic potential as a target to for the development of novel therapeutics for the treatment of breast cancer.
Every year breast cancer kills around 10.000 women in the UK only, underlying the urgency to develop novel therapies for the treatment of the disease. The focus of the project is to help the development of therapeutic strategies to treat IKK-i (inducible IKK or IKK-epsilon) driven tumours, currently 30% of breast cancers. IKK-i (inducible IKK or IKK-epsilon) is a kinase extensively characterised because of its multiple functions: it is required in the innate immune system response, and it activates the survival factor NFkB. Importantly, IKK-i (inducible IKK or IKK-epsilon) has also been implicated in the regulation of energy balance in obese mice, and in addition to these plethora of physiological functions, IKK-i (inducible IKK or IKK-epsilon) has been shown to be a breast and ovarian cancer oncogene.
Rationale: preliminary data from the lab suggest that the oncogenic potential of IKK-i (inducible IKK or IKK-epsilon) has not yet been fully explained. Thus the present PhD project aims to investigate the mechanisms responsible for triggering IKK-i (inducible IKK or IKK-epsilon) activation in respect to this still unexplored aspect of its oncogenic potential. Understanding how IKK-i (inducible IKK or IKK-epsilon) is activated will reveal novel signalling pathways and regulators, which may represent novel targets for drug development.
Chromosomal instability: a question of survival
A feature of most tumour cells is an aberrant number and structure of chromosomes, as a consequence of chromosomal instability (CIN). CIN promotes tumour evolution and chemotherapy resistance, and is generated by defects in the replication and segregation of chromosomes, leading to high rates of chromosome missegregation during mitosis. Non-cancer cells go to great lengths to avoid chromosome missegregation, and additionally employ fail-safe mechanisms to ensure any cells that do missegregate chromosomes stochastically, and become aneuploid, are eliminated from the population (our unpublished observations). CIN cancer cells are therefore dependent on the deregulation of these fail-safe mechanisms to survive high rates of chromosome missegregation, offering a potential therapeutic opportunity to specifically target these cells. However, we currently know very little about the nature of these mechanisms, and how they might be deregulated in CIN cells.
Analysis to date of acute responses to chromosome missegregation has been limited to whole chromosome missegregation induced by mitotic defects. However, we have recently demonstrated an additional, ‘pre-mitotic’ cause of chromosome missegregation and CIN in colorectal cancer; replication stress (Burrell and McClelland, Nature, 2013). Replication stress can result in structural chromosome abnormalities that generate acentric chromosomes and anaphase bridges during mitosis, leading to structural and numerical CIN. Such replication-stress-induced chromosome missegregation events induce cell death or arrest in non-CIN cells but are tolerated in CIN cells (our unpublished observations), however the mechanisms underlying these responses are not yet clear. This project aims to advance our understanding of responses to both mitotic and pre-mitotic causes of CIN, and to use this information to identify mechanisms by which chromosomally unstable tumours survive chromosome missegregation. Targeting these pathways in CIN tumours could form the basis of novel therapeutic strategies to combat the clinical challenges of treating chromosomally unstable tumours
Exploring A Stromal Contribution For PKN Kinases In Tumour Growth And Metastasis
Cancer progression occurs through complex interplay between tumour cells and their environment with key contributions arising from both tumour and host stromal cells. As Rho effectors, the PKN family of protein kinases has been implicated in tumour cell migration, invasion and metastasis. PKN1 and PKN3 are upregulated in many tumours, and have been associated with malignant progression in prostate cancer. Increasing evidence from our work now points to additional roles for PKN in host stromal cells. The proposed project will explore the role of PKNs in cancer progression.
We have now developed a raft of key tools to help us interrogate the in vivo function of all three PKN isoforms. This has lead to some very intriguing preliminary data directly implicating PKN in both tumour growth and also in key developmental pathways. With these tools in place and access to the cutting edge research facilities available at the BCI, this project is primed for a very exciting future. Overall this work will contribute to our assessment of the potential benefits and liabilities of targeting PKN in cancer therapy.
- Can overseas students apply?
- What is the stipend?
- How many projects can I select?
- What is the duration of the PhD Studentships?
- What degree will I receive?
- Are there any English language requirements?
- What are the academic entry requirements?
- When will I find out about the interview?
- If I am successful, when will I start my PhD?
This studentship is only open to UK Nationals, EEA/Swiss migrant workers and non-UK nationals with indefinite leave to remain in the UK who will have three years ordinary residence in the UK prior to the start of the studentship.
In addition to the home/EU tuition fees paid on a student's behalf, the MRC studentship provides a tax free annual stipend of approximately £15,726.
You can contact as many supervisors as you are interested in working with.
You will be expected to complete and graduate within 4 years. Your stipend payment will be for 3 years.
You will be registered at and awarded your PhD degree by Queen Mary, University of London.
If English is not your first language or you do not have an undergraduate degree taught in English, you will need to show evidence of English proficiency.
You need to have or expect to gain a first or upper second-class honours degree or equivalent, in a relevant subject.
Shortlisted candidates will be contacted by the supervisor to go through to the next stage - if you do not hear from us by this date, please assume your application has been unsuccessful. Interviews will be held on the 6 December 2013
These provisionally start on the 1 October 2014.