Gads exerts complex regulatory effects on T cell development and function. To better understand its regulatory roles we have developed new mouse models, with which we can inducibly delete Gads, or to allow expression of unique Gads point mutants in vivo. These mouse models are increasingly integrated into our research and provide a systemic perspective on the regulatory roles exerted by Gads at various stages in the life of a T cell.
Gads dimerization promotes its cooperative binding to LAT, which markedly increases the sensitivity of immune cell signaling. Here, TIRF microscopy was used to visualize the antigen receptor-induced co-clustering of Gads and LAT. We are using this approach as one way of characterizing the protein interfaces required for Gads dimerization, and for its cooperative binding to LAT.
Gads plays an important regulatory role in allergy; indeed, we showed that Gads dimerization is required for allergic responsiveness in a mouse model. We are developing new biophysical assays with which to characterize Gads dimerization and its cooperative binding to LAT. This research direction may lead to the development of novel strategies for the treatment of allergy.
