Netherlands, AMSTERDAM
Internship/Master project: Investigating inhibitory immune receptor activation Work Activities
Inhibitory immunoreceptors play an essential role in maintaining immune homeostasis. In our lab we study leukocyte-associated immunoglobulin-like receptor 1 (LAIR-1), an inhibitory pattern recognition receptor that is activated by collagens and proteins with collagen-like domains. These ligands can be presented to LAIR-1 in several forms, including stiff collagen fibers, diffusing membrane proteins, and soluble secreted proteins, each with markedly distinct mobility profiles.
Current models propose that LAIR-1 is activated via ligand-induced receptor clustering. While ligand mobility is known to influence T and B cell receptor activation, the impact of ligand mobility on LAIR-1 clustering and activation has not been established. In addition, the potential roles of force sensing and actin flow in LAIR-1 clustering are unclear. This project aims to uncover how ligand mobility and associated mechanical cues shape LAIR-1 clustering and activation.
The first step of the project will be to fluorescently label a stimulating antibody against LAIR-1. After verifying that the labelled antibody is still functional using reporter cells, you will explore the effects of ligand mobility on LAIR-1 activation through single-molecule total internal reflection fluorescence (TIRF) microscopy. This will involve quantitative analysis of LAIR-1 clustering and downstream signalling. The experimental findings will guide further studies aimed at developing an updated model of LAIR-1 activation.
About the group
The internship will be conducted in the Physics of Cellular Interactions (PCI) group, headed by dr. Kristina Ganzinger. Our group focuses specifically on processes that are critical to communication in the immune system. We address these questions mainly by reconstituting signalling processes in model-membrane systems, developing novel experimental platfo...
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