The functional characterization of the tumour suppressor gene CSMD1 in breast cancer

Project description

CUB and Sushi multiple domains protein 1 (CSMD1) maps to 8p23, a region deleted in many cancers including breast cancer. Our previous work has established that CSMD1 is an independent prognostic marker in ductal breast cancer, with reduced expression associated with high tumour grade and poor survival1. CSMD1’s function is unknown; however, our data suggests that CSMD1 is involved in a signaling cascade regulating a wide range of cell processes involved in cancer development. 

 

We have already generated shRNA and CRISPR cell lines with reduced CSMD1 expression to investigate the function of CSMD1. Analysis of these cell lines has shown that suppression of CSMD1 expression disrupts cell morphology, in an effect resembling the epithelial-mesenchymal transition (EMT), increases cell proliferation, and enhances cell migration and cell invasion2. We have also established an MCF10A three-dimensional culture model with reduced CSMD1 expression which revealed that loss of CSMD1 expression resulted in the development of larger and more poorly differentiated breast ductal structures2.  In addition, we have also recently developed an in vivo model with reduced CSMD1 expression. Our aims will be to investigate the role of CSMD1 in metastasis which is the primary cause of cancer-associated mortality. We will study the mechanisms behind the function of CSMD1 in EMT, tumour migration and invasion using our 3D culture and in vivo models.

You will gain experience of a broad range of molecular and cell biology laboratory techniques including CRISPR, cell culture of 3D models, confocal microscopy, live cell imaging, Gene expression analysis, RT-PCR, pathway analysis, Western blotting, in vivo work, migration and cell invasion assays, immunohistochemistry and immunofluorescence.

References:

1. Kamal M, Shaaban AM, Zhang L, Walker C, Gray S, Thakker N, Toomes C, Speirs V, Bell SM. Loss of CSMD1 expression is associated with high tumour grade and poor survival in invasive ductal breast carcinoma. Breast Cancer Res Treat (2010) 121(3):555-63.

2. Kamal M, Holliday DL, Morrison EE, Speirs V, Toomes C, Bell SM. Loss of CSMD1 expression disrupts mammary duct formation while enhancing proliferation, migration and invasion. Oncology Reports (2017) Jul;38(1):283-292.

Entry requirements

This project is available immediately to both Home/EU rate applicants and International applicants who are have a sponsor or are able to self-fund their studies. You must be able to provide the appropriate level of fees based on their fee status plus laboratory consumables costs per year. This is in addition to the provision of personal living expenses.

You should hold a first degree equivalent to at least a UK upper second class honours degree in a relevant subject.

Candidate whose first language is not English must provide evidence that their English language is sufficient to meet the specific demands of their study, the Faculty minimum requirements are:

•      British Council IELTS - score of 6.5 overall, with no element less than 6.0

•      TOEFL iBT - overall score of 92 with the listening and reading element no less than 21, writing element no less than 22 and the speaking element no less than 23.

Applicants with sufficient funding must still undergo formal interview prior to acceptance in order to demonstrate scientific aptitude and English language capability.

How to apply

Applications can be made at any time. To apply for this project applicants should complete a Faculty Scholarship Application form and send this alongside a full academic CV, degree transcripts (or marks so far if still studying) and degree certificates to the Faculty Graduate School fmhgrad@leeds.ac.uk

We also require 2 academic references to support your application. Please ask your referees to send these references on your behalf, directly to fmhgrad@leeds.ac.uk

If you have already applied for other scholarships using the Faculty Scholarship Application form this academic session you do not need to complete this form again. Instead you should email fmhgrad@leeds.ac.uk to inform us you would like to be considered for this scholarship project.

Any queries regarding the application process should be directed to fmhgrad@leeds.ac.uk.

How to apply (email)

fmhgrad@leeds.ac.uk.