Barbara A. Baird

<TITLE>Barbara A. Baird</TITLE> <CENTER><TABLE BORDER=0 ALIGN=CENTER VALIGN=TOP CELLPADDING=10> <TR>  <TD VALIGN=MIDDLE><B><H2><CENTER>Barbara A. Baird</CENTER></H2><HR> <H3>Professor of Chemistry<BR> <A HREF="http://www.chem.cornell.edu/">Department of Chemistry</A><BR> Cornell University</H3></TD> </TR> </TABLE> </CENTER> <HR> <BR> <BR><strong>Research Interests</strong><br> 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. As described below, current studies focus mainly on three receptor systems that operate in immunological and other inflammatory responses. The goal of these integrated studies is to understand these complex biological systems on a molecular level; the information obtained also has important biomedical applications in drug design and clinical therapies. <P> 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). The physical and biochemical events that immediately follow receptor aggregation involve an alteration in the interaction of the receptor with other cellular components. Fluorescence resonance energy transfer (FRET) and anisotropy studies with IgE and genetically engineered IgE variants have revealed that IgE has a rather rigid, bent structure before and after binding to its membrane receptor. Ongoing studies are examining the structural orientations of IgE-receptor complexes as they aggregate into a triggering configuration. The kinetics and thermodynamics of binding and cross-linking between cell-bound IgE and structurally defined multivalent ligands are measured with fluorescence methods and analyzed in detail with supercomputer fitting to theoretical models. Quantitative fluorescence microscopy and very bright fluorescent probes allow monitoring of the lateral diffusion of membrane receptors and changes in the dynamics of individual receptors on the cell surface that accompany receptor cross-linking and cellular activation. Phosphorescence anisotropy measurements detect the corresponding changes that occur in the rotational motion of receptors. These physical approaches have revealed interactions between cross-linked receptors and other cellular components that may be involved in the signal transduction mechanism. Chemical cross-linking reagents together with a variety of chromatographic methods are being used to investigate the molecular composition of the complexes formed with the receptors. The biochemical activities induced by activated receptors (e.g., protein kinases and phosphatases, phospholipases, Ca2+ mobilization) are measured in parallel and related to the physical changes observed. One current thrust of these integrated studies is elucidating the apparent importance of membrane architecture in the signal transduction process. <P> The receptor for antigen on T-cells (TCR) provides the means by which T-cells recognize and kill the target cells bearing the foreign antigens, or stimulate other immunological responses to fend off the invasion. Similar to FceRI receptors, cross-linking of TCR receptors appears to play 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 being investigated with the experimental methods established and under development in this laboratory. For example, FRET is being used to map the dispositions of TCR subunits and monitor TCR aggregation together with accessory molecules. TCR association with the membrane structure and cytoskeleton is also being investigated. <P> The soluble cytokine interleukin-1 (IL-1) stimulates a large variety of cells in the manifestation of immunological and inflammatory responses. FRET measurements in the Baird lab recently revealed that IL-1 causes aggregation of its receptor. Further characterization of this process is ongoing and the aggregation is being compared with IL-1 binding properties and stimulated cellular activities. <P> <strong>Research Projects</strong> Experimental and theoretical studies of bivalent and multivalent ligands binding to cell surface receptors; investigation of binding properties that are critical for cell activation. <P> Biophysical and biochemical characterization of specialized membrane domains involved in cellular signaling; methods include confocal fluorescence microscopy, sucrose gradient centrifugation of cell extracts, Western blotting of immunoprecipitates and biological assays. <P> Measurements of cell surface receptor dynamics and redistributions with quantitative fluorescence microscopy, including single particle tracking. <P> Investigation of receptor aggregation as it relates to ligand binding properties and subsequent cellular events with fluorescence spectroscopy and flow cytometry and biological assays. <P> <A HREF = "Baird_CV.html">Curriculum vitae and selected publications</A><BR><P> <BR> <CENTER><A HREF = "../cornell_pharmacology.html">Field of Pharmacology Home Page</A></CENTER> <BR> <HR> <BR> <TABLE BORDER=0 ALIGN=LEFT VALIGN=TOP CELLPADDING=5> <TR> <TD VALIGN=TOP><IMG Align=Top SRC="../faculty_pictures/baird_low.jpeg"></A></TD> <TD VALIGN=MIDDLE> <PRE>Barbara A. Baird Department of Chemistry 460-A Olin Laboratory Cornell University Ithaca, New York 14853 USA <a href=mailto:bab13@cornell.edu>e-mail</a>: bab13@cornell.edu phone: 607-255-4095 FAX: 607-255-4137 </PRE> </TD> </TR> </TABLE>