Barbara Baird, Chemistry & Chemical Biology

The Baird laboratory employs a broad range of biophysico-chemical methods to investigate the structure and molecular mechanisms of cell membrane receptor proteins. This biophysical characterization is carried out in conjunction with measurements of cellular activities so as to determine what features are critical for the initiation and regulation of signal transduction. Current studies focus on three receptor systems that operate in immunological and other inflammatory responses. The goal of these integrated studies is to understand complex biological systems on a molecular level; the information obtained also has important biomedical applications in drug design and clinical therapies.

The mast cell surface receptor FceRI binds immunoglobulin E (IgE) with high affinity to mediate the release of histamine from intracellular granules during the allergic immune response. The critical event in the process is the aggregation of a few receptor molecules, which is initiated in vivo by the molecular bridging of receptor-bound IgE with multivalent ligands (antigens). Receptor aggregation is succeeded by alteration in the interaction of the receptor with other cellular components. Fluorescence resonance energy transfer (FRET) and aniso-tropy studies with IgE and genetically engineered IgE variants reveal that IgE has a rigid, bent structure before and after binding to its membrane receptor.

The receptor for antigen on T-cells (TCR) enables T-cells to recognize and kill target cells bearing foreign antigens or stimulate other immunological responses to fend off invasion. Similar to FceRI receptors, cross-linking of TCR receptors plays an important role in cellular activation, and many of the same biochemical activities are involved in the signal transduction process. These similarities, as well as the structural and mechanistic features unique to the TCR system, are investigated with experimental methods developed in this laboratory. For example, FRET is being used to map the dispositions of TCR subunits and monitor TCR aggregation with accessory molecules. TCR association with the membrane structure and cytoskeleton is also being investigated.

The soluble cytokine interleukin-1 (IL-1) stimulates a variety of cells in the manifestation of immunological and inflammatory responses. FRET measurements in the Baird lab revealed that IL-1 causes aggregation of its receptor. Further characterization of interactions occurring in this process is ongoing, and compared with IL-1 binding properties and stimulated cellular activities.