The role of actin-regulatory proteins for mast cell mediated allergic reactions

• Applicant: Dr. Niko Föger
• Subject Area: Dermatology
• Term: from 2013 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 231357495

Allergies are a serious and growing health issue. As critical effector cells, mast cells play a pivotal role in allergic disorders. While it has long been recognized that mast cell activation and subsequent mediator release are associated with changes in actin cytoskeletal organization, the precise role of actin cytoskeletal dynamics for mast cell function and the molecular mechanisms involved are is still largely unknown. Utilizing a genetic approach, we have previously described the regulation of mast cell function by actin-regulatory proteins, i.e. coronin. This proposal aims at further defining the role of actin-regulatory proteins for mast cell function and allergic reactions. To this end, we propose to study the role of the actin-regulatory protein HS1 in mast cell biology. In our studies we will employ a dual strategy, in which cell biological in vitro studies are complemented by the in vivo analysis of allergic reactions in HS1-deficient mice. Specific aims of this proposal are (1) the functional characterization of HS1-deficient mast cells by studying FceRI-induced mast cell degranulation, cytokine production and signaling characteristics; (2) a mechanistic analysis of the role of HS1 phosphorylation and actetylation for mast cell function and (3) the analysis of the physiological role of HS1 for anaphylactic responses in vivo. Together, the proposed experiments will add important new information to our understanding of mast cell biology and may reveal how perturbations in these processes may contribute to the pathophysiology of allergic disease.

• DFG Programme: Research Grants