Nicole McDermott

Profile

My undergraduate studies were carried at the Universtiy of York where I studied biology, here I developed and interest in cancer cell biology and immunology. I spent my placement year working in the School of Clinical Dentistry, University of Sheffield in Dr Lynne Bingle's group. The aim of the project was to look at the function of BPIF2A and BPIF2B which are salivary glycoproteins involved in innate immunity within the oral cavity in defence against bacterial infections. The project involved DNA cloning to produce recombinant wild-type and mutant forms of BPIF2A (disrupted N-glycosylation sites). The mutant forms had either one or both of the N-glycosylation sites disrupted by site-directed mutagenesis (SDM) thought to affect their binding ability, the constructs were analysed using western blotting to determine whether the process had been successful. Once this was confirmed I then used the constructs for transient transfection of HEK293 cells with the constructs, then collected the secreted protein for analysis using pull-down assays. The pull-down assays were carried out with S.aureus, S.gordonii, E.coli and S.mutans.

My final year project was undertaken with Professor Norman Maitland studying the development of prostate cancer; the project will involve the use of the CRISPR/Cas9 system to generate mono- and bi-allelic knockouts of the ELF3 gene. During this project I have used CRISPR/Cas9 gene editing techniques, along with human cell culture and transient transfections, along with some genetic techniques such as RT-PCR and qPCR. The aim of the project was to generate mono- and bi-allelic knockouts of ELF3 in a prostate cell line, I used qPCR to determine ELF3 copy number to decide on the most appropriate cell line to use. Transduction using a lentivirus was used to introduce the CRISPR/Cas9 system followed by puromycin selection and a colony forming assay.

Research interests

Currently my PhD research with Prof. Reuben Tooze is in B cell biology specifically in their adhesion and differentiation capabilites and how this may be disrupted in B cell malignancies. In particular I will be looking into expression of adhesion molecules in mutliple myeloma (MM), extramedullary plasmacytoma (EMP) and plasmablastic lymphoma (PBL). MM is a cancer that develops from plasma cells in the bone marrow (BM) and leads to the formation of osteolytic lesions throughout the skeleton, currently MM is treated with chemotherapy but has high rates of relapse. Known risk factors for developing MM are having MGUS or SMM, which are asymptomatic plasma cell neoplasms and obesity. EMPs are plasmacytomas found in soft tissue and tend to be located in the head and neck, they are isolated tumours formed from neoplastic plasma cells and can be seen alongside MM, they are potentially curable and treated with radiotherapy. Plasmablastic lymphomas are formed from a immature B cell that is thought to be caught somewhere between a plasmablast and a fully differentiated plasma cell, therefore deciding on an appropriate treatment can be problematic, currently PBL has a poor prognosis. 

Previous work carried out in the Doody/Tooze lab identified an adhesion signature expressed more highly in EMP compared to PBL, we hypothesise that expression of adhesion molecules may provide a way of differentiating between neoplasms and indicate to a better prognosis. We are particularly interested as to whether the expression of adhesion molecules influences tumour formation or localisation, as EMPs present isloated tumours that are generally easier to treat and respond well to radiotherapy, having expresssion of these adhesion molecules may be beneficial. The adhesive properties that lead to an isolated tumour and therefore easier to treat could then be utilised to help predict prognosis or progression to developing MM. I am currently looking at two different sets of adhesion molecules, one set is to be used hopefully as an addition to the current diagnostic markers for classification of B cell neoplasms and as a predictor of prognosis the other is the Protocadherin-gamma family and how their expression may influence cell-cell interactions by providing single cell identity.

Qualifications

• BSc (Hons) Biology with a placement year