Institute of Molecular Genetics of the Czech Academy of Sciences
Our laboratory is focused on understanding the molecular mechanisms governing signal transduction from the plasma membrane receptors to the cytoplasm. High-affinity immunoglobulin E receptor (FcεRI), cKIT, and G protein-coupled receptors (GPCRs) are plasma membrane receptors involved in the degranulation and/or chemotaxis of mast cells, potent immune modulators of the tissue microenvironment. Within minutes of antigen-mediated activation, mast cells release various preformed biologically active compounds, followed by a wave of mediator synthesis and secretion. Increasing evidence suggests an intricate network of inhibitory and activating receptors, specific signalling pathways, and adaptor proteins whose overall signalling balance governs the mast cell responsiveness to particular stimuli.
Our recent studies focused on understanding the role of plasma membrane signalosomes and selected cytoplasmic proteins during mast cell activation through the FcεRI, cKIT, and GPCRs. To reach our goal, we used various techniques of molecular biology, immunology, immunochemistry, and immunohistochemistry. Our principal approach lies in the production of cells or animals with increased or reduced expression of selected genes and comparison of their properties with wild-type cells or wild-type animals.
We found and described new functions of the members of ORM family proteins, tetraspanins, transmembrane adaptor proteins PAG and NTAL, and cytoskeletal protein 4.1R in mast cell signalling. Our studies aim to deepen the knowledge of the cellular and molecular mechanisms involved in allergic and inflammatory diseases. Our long-term goal is to contribute to the development of new, more potent, anti-allergic and anti-inflammatory drugs.
