Department of Biomedical Science projects

Intercalated BSc Medical Sciences Research available projects

Biomedical Science anatomy image

Projects:

Epithelial cell plasticity in development and tumour progression

Main Supervisor:

Dr Kyra Campbell

kyra.campbell@sheffield.ac.uk

Second Supervisor:

Dr Mirre Simons

m.simons@sheffield.ac.uk

Type of Project:

Lab/Bench Project - primarily working in a lab environment

Aims and Objectives:

Although 90% of cancer deaths are caused by metastasis, the underlying pathogenic mechanisms are poorly understood. Cell plasticity is the ability of cells to reversibly change their phenotype and plays a critical role at multiple steps in the complex process of tumour dissemination, which relies on cells undergoing an epithelial-to-mesenchymal transition (EMT), migrating away from the primary tumour and later undergoing a reverse mesenchymal-to-epithelial transition (MET). While several transcription factors that regulate EMTs have been isolated, how these actually impinge on the cellular responses underlying cell plasticity remains poorly understood. Even less is known about MET: we have so far failed to identify the signals required for its induction, nor do we understand how it occurs at the cell and molecular level.

The selected BMedSci student will work on a project targeted towards identifying the molecular mechanisms underlying MET during development and tumour progression. The project will involve studying how this fundamental property is orchestrated during morphogenesis of the Drosophila midgut, and also in exciting Drosophila cancer models that we have recently generated.

The lab is currently carrying out a high-throughput expression screen for genes involved in MET in the Drosophila embryo. The aim of this project will be for the student to screen a number of candidates for a functional role in MET. Key objectives will be to identify a novel biological process or gene required for MET; to characterise at the subcellular level in vivo the precise role of these factors during tissue morphogenesis; to test for a role of these candidates in pathological METs during tumour metastasis in our Drosophila model.

Research Methodology:

This project will combine molecular biology with powerful Drosophila genetics, quantitative image analysis and cutting-edge high-resolution microscopy on our own dedicated multiphoton confocal. It will also involve making targeted Drosophila mutants using CRISPR, and analysing their effects at the subcellular level in fixed and living samples. This is a unique opportunity for you to carry out state-of-the-art microscopy, and develop your skills in an exciting multidisciplinary environment.

Expected Outcome:       

The lab is currently carrying out a high-throughput expression screen for genes involved in MET in the Drosophila embryo. We expect the student to screen a number of candidate genes for a functional role in MET and provide a precise characterisation of the phenotype in mutant situations for each of the candidates. For a positive hit, we expect the student to make new tools for studying the gene, which will involve molecular biology including cloning and CRISPR as well as genetics. Finally, we expect the student to develop skills in high-resolution real-time imaging, that they will use to characterise cell behaviour at the sub-cellular and tissue level.

Additional Training:

We will offer the student in-depth training in imaging cells, tissues and whole embryos in both fixed and real-time at both the sub-cellular and tissue level, as well as quantitative image analysis. This is a unique opportunity due to the fact that the lab has their own dedicated multi-photon confocal, especially suited to deep-tissue imaging. We will also provide additional training in genetics, embryology, molecular biology and also in the use of Drosophila as a model for cancer.

Ethical Approval:

Non-human tissue - no ethics approval required.

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