Once a foreign invader is recognised by our immune system, the next stage is the activation of an appropriate response to deal with the threat. Typically, a complex signalling mechanism is triggered that involves dynamic spatial organisation of a network of molecules, clusters and vesicles that then result in downstream activation responses.
How does putting a ligand on a receptor generate a signal for the T cell? How do we go from one signal at the cell surface to the activation of an immune response?
It is the steps in between that determine how T cells respond to certain stimulae. T cell functionalities are programmed to either activate or not, depending on the stimulae i.e. will an immune response be triggered. Imaging Centre scientists have developed expertise in understanding the different stages of these large and complex signalling networks.
Imaging CoE scientists at the UNSW node aim to bridge the gap between structural biology and cellular function, particularly to decipher single molecule dynamics and dynamic interactions (how cells sense and react to their environment) as well as single molecule imaging of intact cells.
This research program addresses questions such as: How do cells employ forces? How do these cells interact with other molecules? How do signalling interactions switch biochemical functions? How do ligand-receptor interactions lead to signal initiation?
The group seeks to understand the processes that lead to the activation, migration and clustering of T-cells, their interactions with the extracellular matrix and the potential applications of this knowledge to biomedicine.
Missing from the molecular biological approaches, however, is an understanding of how mechanical forces affect their interplay. By monitoring the localisation, structure, interaction and the dynamics of biomolecules Imaging CoE scientists aim to understand their function in model systems as well as in living cells.
Cell-expressed integrins mediate adhesion with other cells and with extracellular matrix and are essential for embryonic development and for controlling leukocyte migration in later life. Using single molecule techniques, Centre AI Jeremie Rossy and CI Kat Gaus were part of a team of researchers who revealed what controls clustering of integrins on the cell membrane and that the activation state of individual integrins can be switched off. They also found that disruption of this pathway caused autoimmune phenomena.
Dynamic control of β1 integrin adhesion by the plexinD1-sema3E axis. PNAS, Jan 2014
Authors: YI Choi, JS Duke-Cohan, W Chen, B Liu, J Rossy, T Tabarin, L Ju, J Gui, K Gaus, C Zhu, EL Reinherz
Danny Hatters, Till Boecking, Jeremie Rossy