As a postdoc in our Physics of Cellular Interactions group headed by Dr. Kristina Ganzinger, you will analyse the spatiotemporal dynamics of CAR T cell signalling both in live cells and by reconstituting the signalling pathways in vitro from the bottom-up. To do so, you will also develop new model systems for cell-cell contacts and continuously push the boundaries of single-molecule fluorescence microscopy.
Equipping T cells from patients with chimeric antigen receptors (CARs) has promised a new era of cancer therapies. CARs are synthetic transmembrane receptors that are designed to recognise a tumour antigen and activate T cell signalling pathways, directing T cells against the tumour. However, despite the quick success of specific CAR designs, it has become clear that it is extremely difficult to predict how changes to CAR designs affect their signalling and therefore efficiency. This lack of predictability is, at least in part, due to our very limited understanding of the molecular mechanisms of CAR signalling.
The aim of this project is to reveal the dynamics of CAR function and signalling for the first time at the single-molecule level. You will use advanced single-molecule and single-cell imaging combined with novel synthetic biology approaches to directly measure the striking hypothesized CAR organisation into signalling clusters in membranes and downstream signalling dynamics.
This project has now become possible owing to recent technical advances, including a new single-molecule tracking method based on DNA-PAINT that we recently co-developed (Nat Commun 2021), new in vitro assays, and imaging approaches developed by our lab and others (JACS 2013, Nat Immun 2016, PNAS 2019). You will develop new microscopy-based assays, and help design innovative lipid biochemisty methods to enable this first dynamic view on how CARs re-wire T-cell signalling cascades and to identify design principles for tuning CAR activation.
We are looking for an experimental (bio)chemist or molecular immunologist with a strong interest in biophysical questions, or a biophysicist who has already worked with single-molecule fluorescence techniques. Experience with protein purification and/or model lipid systems is highly desired; knowledge of quantitative fluorescence microscopy / automated data analysis would be an advantage. You should like the idea of working in a collaborative, ambitious and international environment.
Formally, you need to meet the requirements for a doctors-degree and must have research experience in a non-Dutch academic environment.
dr. KA (Kristina) Ganzinger
Group leader Physics of Cellular Interactions
Phone: +31 (0)20-754 7100
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