On the Molecular Mechanisms of Cancer pathway you will be taught the essentials of conducting high quality research through a range of core modules, and will gain a detailed knowledge of cancer before undertaking your research project. 

biomedical science students in a lab

The MRes is made up of 180 credits. All modules are compulsory, and will equip you with the skills and knowledge to conduct high quality research. 

Core modules

Research methods 15 credits
Statistics 15 credits
Research project planning and management 15 credits
Research project 105 credits

Specialist module - Molecular Mechanisms of Cancer

This 30 credit module will provide a basic introduction to the normal functioning of relevant cellular pathways and an indication of how problems can arise. You will then be able to select an individual project and carry out detailed original research into your chosen area.


The module will develop your understanding of the fundamental cellular and molecular principles governing tumorigenesis, and of how the biology of cancer has led – and will continue to lead – to new therapies.

This pathway will take advantage of active research taking place at St George’s in a wide variety of cellular and molecular processes that are compromised in cancer. This will allow you to explore the key scientific advances that have led to the modern view of cancer as a disease of altered cell signalling arising from DNA damage. The module will also give you insight into how new sequencing technologies and ‘omics’ methodologies are providing novel insights into susceptibility to and development of cancer.

Past research projects

The substantive research project is worth 105 credits. Here are some examples of past student projects:

The cAMP pathway in regulation of melanocyte differentiation: implications for skin cancer

Aim:  To determine the effects of cAMP agonists on pigmentation of hypopigmented melanocytes in disorders of melanosome biogenesis.

Brief overview: A hallmark of melanocytes is their ability to produce pigment (melanin) in specialised lysosome-related organelles (melanosomes) in response to UV radiation and growth factors. Several genetic disorders involving abnormalities in skin and/or hair pigmentation are associated with defects in formation and trafficking of melanosomes. These disorders include Hermansky-Pudlak Syndrome (HPS), disorders of organelle biogenesis, and respective mouse models, which are playing central roles in current studies of protein trafficking and organelle assembly. Based on our data we will expand our investigation (Nature, 2008) and study the effect of cAMP agonists on the routing of tyrosinase, an enzyme that catalyses the production of melanin, in BLOC-1, -2 and -3-deficient melanocytes, models of HPS. Our studies will focus on the effects of cAMP agonists on pigmentation of BLOC-1, -2 and -3-deficient and wild-type melanocytes assessed by light and fluorescence microscopy. Our findings might help in understanding and developing a general mechanism of protection from damaging effects of UV radiation, and thus increase our knowledge of skin cancer prevention.

Methods used for data collection: Advanced mammalian cell culture. Measures of cell proliferation and differentiation. Immunostaining. Light and fluorescence microscopy.

What is the role of the human TTC4 protein in apoptosis, proliferation and cancer?

Brief overview: TTC4 is a human protein that is highly expressed in tumour cell lines. Mutations in TTC4 show correlation with a poor prognosis for the progression of malignant melanoma. We have shown that it is a co-chaperone for the Hsp90 protein chaperone machinery and most likely acts in the interaction of Hsp90 with specific ‘client proteins’. Possible client proteins with which it interacts (cdc6,bag6,msl1, hnRNPk) have functions in several of the processes which are hallmarks of cancer – proliferation, genome stability and apoptosis – suggesting that TTC4 may also function in these processes. 

Consistent with this, TTC4 is broken down during apoptosis and alterations in the protein appear to cause changes in both proliferation and apoptosis. The aim of this project is to analyse the role of TTC4 in these pathways in more detail with a view to getting a better understanding of the involvement of TTC4 in cancer. We will approach this from two directions by making changes in the TTC4 protein: we will map the regions of TTC4 which interact with its client proteins, and attempt to generate mutations in the protein which prevent its interaction with the clients. If time permits, one of more of these mutations will be introduced into cell lines in culture. These will be monitored for changes in well-defined markers for proliferation and apoptosis and functional changes in TTC4 interacting proteins. 

We will also investigate ways of reducing the level of TTC4 in cells by shRNA/CRISPR based methodology and if successful will observe how this affects cellular function by making changes in the client proteins. The problem with the above approach is that we may not be able to distinguish the TTC4 interacting regions for the different client proteins. Therefore, to understand the pathways involved in the cellular effects of TTC4 we will have to study individual client proteins. A previous student in the lab has already done some preliminary mapping on the interactions between TTC4 and cdc6, msl and hnRNPk. We will now carry out more precise mapping of the interacting regions and again attempt to generate mutations in the client proteins which prevent their interaction with TTC4. Again if time permits, we will look at the effect of these mutations in the client proteins on their individual function, as well as proliferation and apoptosis. 

Methods used for data collection: Basic molecular biology techniques (e.g. cloning , pcr, use restriction enzymes etc), basic protein analysis techniques (eg protein extraction, protein gels, protein blotting, immunoprecipitation), two hybrid assays, cell culture and manipulation, proliferation apoptosis and cell invasion assays.

Analysis of the defects in replicative DNA polymerases linked to cancer predisposition and tumour development

Brief overview: Recent findings have highlighted that defects in the DNA polymerases that are involved in bulk chromosome replication (polymerases delta and epsilon) contribute to the development of colorectal and endometrial cancers. The precise mechanisms by which they do this, however, remain unknown. In this project, we will directly analyse the properties of one or more of the polymerase germline mutations which show this cancer predisposition and determine how they differ from the wild type protein. We hope that these analyses will shed light on the way that these particular mutations generate the genome instability.

To do this we will: make mutations in the large subunit of the human DNA polymerase epsilon equivalent to germline mutations that have been identified as causative for colorectal cancer; purify both wild type and mutant proteins; and compare the wild type and mutant proteins for biochemical properties such as defective proofreading, misincorporation of modified bases, misincorporation of riboNMPs, polymerase switching, polymerase stalling and need for fork restart.

Methods used for data collection: Basic molecular biology techniques (e.g. cloning , pcr, use restriction enzymes etc), basic protein analysis techniques (eg protein extraction, protein gels, protein blotting, immunoprecipitation), Sf9 cell culture, use of baculovirus vectors, design and analysis of enzyme assays.

Last Updated: Tuesday, 21 March 2017 09:24