Undergraduate student projects

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How do T cells sense the strength of activating signals during an immune response?

T cells are key players of the immune system and are able to respond appropriately to different pathogens. T cell activation is initiated when the T cell receptor (TCR) is bound by an antigen, triggering clustering and phosphorylation of the TCR and downstream intracellular signalling pathways. This project will investigate differences in early signalling events when T cells are more or less activated and how these events may translate the strength of the signal to the inside of the cell. This project will exploit model membranes which present different antigens to T cells, combined with cutting-edge microscopy techniques.

Supervisors: Prof Katharina Gaus, Dr Sophie Pageon

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How does T cell signalling begin?

To participate in an immune response, T cells are activated when the T cell receptor (TCR) recognises an antigen and triggers an intracellular signalling cascade. The TCR is phosphorylated by the kinase Lck that yo-yos in and out of clusters (Rossy et al. Nature Immunology 2013). The goal of this project is to investigate how Lck finds and interacts with the TCR. The project uses model membranes into which recombinant Lck and TCR subunits are incorporated as well as T cells and a range of imaging tools such as single molecule localisation microscopy and single particle tracking.

Supervisors: Prof Katharina Gaus, Dr Jérémie Rossy

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How can we count protein subunits?

Single-molecule localisation microscopy (SMLM) is an excellent method for generating super-resolution fluorescence images for viewing features only a few nanometers in size. Due to the complex photophysics of the fluorophores it has not been possible to extract quantitative information regarding label targets, such as the number of protein subunits in a complex. The goal of this project is to develop a new method for quantitative super-resolution microscopy to extract this information. This project will utilise single-molecule spectroscopy and SMLM as well as a image analysis in matlab.

Supervisors: Prof Katharina Gaus, Dr Philip R Nicovich

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Building next-generation microscopes

The imaging demands in our lab demand instruments with superior precision and flexibility. Commercially-available instruments are inadequate so it is up to us to build them. The goal of this project is to design, implement, and optimise of one or more cutting-edge super-resolution fluorescence microscopes. This project requires knowledge of optics, electronics, and instrument control software programming.

Supervisors: Prof Katharina Gaus, Dr Philip R Nicovich

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Imaging membrane nanodomains and endosomes in T cells

We think that the immune synapse between T cells and antigen presenting cells shares more than just the name with the neuronal synapse. Although the concept of signalling endosomes has first been elaborated for neutroptrophic factors, today accumulating evidence points towards the internalisation of engaged T cell receptors to amplify and control signalling during T cell activation. We want to understand how the T cell membrane is locally modified to specifically package engaged receptors into signalling endosomes. The PhD candidate will use super-resolution and advanced live cell microscopy to establish the contributions of membrane packing, curvature and charge to this process. The aim of this project is to determine the molecular mechanisms connecting the 2D organisation of the plasma membrane to the 3D architecture of the endocytic matrix.

Supervisors: Dr Jérémie Rossy and Prof Katharina Gaus