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  Role of the Rho GTPase RhoD in cancer

   School of Cellular and Molecular Medicine

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  Prof Anne Ridley  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

Epithelial cancers such as breast cancer become difficult to treat when they invade the surrounding tissues, eventually entering the blood stream and spreading to other parts of the body to form metastases. Rho GTPases are a family of 20 intracellular signalling proteins, some of which are well known to contribute to cancer progression. For example, we have demonstrated key roles of the Rho GTPases RhoC, RhoH and Cdc42 in prostate cancer and breast cancer cell migration and invasion.

This project will build on recent published results from our laboratory showing that high levels of RhoD, a little characterized Rho GTPase, increases the risk of breast cancer development (Kazmi N, Robinson T, Zheng J, Kar S, Martin RM, Ridley AJ (2022) Rho GTPase gene expression and breast cancer risk: a Mendelian randomization analysis. Scientific Reports 12, 1463).

RhoD has been implicated in membrane trafficking but has not yet been tested for a role in cancer. We hypothesise that increased RhoD expression in breast epithelial cells stimulates their proliferation and invasion through changes in membrane expression of receptors, leading to cancer progression.

To address this hypothesis, the following experiments will be carried out:

1. Movies of RhoD-overexpressing normal breast epithelial cells and breast cancer cells with and without RhoD expression will be made using timelapse microscopy. Cell divisions and cell number in these movies of will be measured to find out whether there is an increase in cell proliferation.

2. Breast epithelial cells and cancer cells will be grown as spheroids in 3D for and their growth and invasion monitored over time with and without overexpression of RhoD.

3. Known RhoD-interacting proteins will be tested for their effects on spheroid growth and invasion.

4. Proteomic analysis of membrane receptors on the surface of cells with and without expression of RhoD will be carried out to identify changes induced by RhoD.

5. Receptors identified in the proteomic analysis will be analysed for their effects on breast epithelial cell proliferation and invasion.

Together, these experiments will for the first time define the role of RhoD in breast cancer and determine the signalling pathways contributing to RhoD function in cancer.

MSc by Research (MScR) is a 1-year research degree that provides an intensive lab-based training and a preparation for PhD study. You will carry out your studies as part of your research group – like a PhD student does. Towards the end of the year, you write up a thesis on your research and are examined on this. This degree suits students wanting to gain maximum research experience in preparation for PhD applications. 

We are keen to recruit a diverse range of students and to ensure our research is open to all. We particularly welcome applications from groups traditionally under-represented in life sciences research. Please check the University webpages for the current tuition fee information. Most MScR projects also require a bench fee. This varies depending on the research and your project supervisor can tell you the bench fee for the project.

How to apply:

Use the following link to apply: Start your application | Study at Bristol | University of Bristol

You should select the programme: Cellular and Molecular Medicine (MSc by Research) or Cellular and Molecular Medicine (PhD) (3yr)

Please ensure you upload all supporting documents as per the admissions statement (which applies to both PhD and MScR programmes): PhD Cellular and Molecular Medicine | Study at Bristol | University of Bristol

Clearly indicate the supervisor name and project title in the relevant section of the application form.

The system will not allow you to submit your application without uploading a document to the research statement section.  Where this is an optional requirement, please upload a blank Word document which is headed “No research statement required”.

Applications are accepted all year round. However, the preferred entry points for study are September / January / April / July.

Biological Sciences (4)

Funding Notes

This project is available to:
- international students who wish to self-fund their PhD or who have access to their own funding
- UK or international students who wish to self-fund their MScR or who have access to their own funding
Please contact Dr Ridley directly for information about the project and how to apply ( [Email Address Removed]).

Where will I study?

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