has collaborator
- Center for Infectious Disease and Immunity Center
- Wandinger-Ness, Angela Professor
Overview. I am formally trained in experimental physical chemistry specializing in laser spectroscopy and the measurement of fast electron and energy transfer processes in molecular complexes. My expertise in cell biology was gained through a 5 year NIAID-funded Mentored Quantitative Research Development Award (K25) entitled “Membrane Organization in Cell Signaling and Adhesion”. My long-term scientific interests are to understand mechanisms that govern the responses of cells to a wide range of environmental stimuli. These interests have been shaped through interactions with mentors and colleagues in the areas of cell signaling adhesion, trafficking, virology and drug discovery. The experimental approaches are inherently interdisciplinary and collaborative. We use a variety of novel nanotechnologies and quantitative fluorescence measurement capabilities, which include real time quantitative nanoscopic FRET measurements by flow cytometry and live cell microscopy imaging. In collaboration with the NIH Roadmap New Mexico Center for Molecular Discovery, we are engaged in efforts to develop flow cytometry based high throughput screening (HTS) assays for small molecule inhibitors of viral entry. Unified themes are being pursued under the areas described below.
Membrane Organization. We are interested in establishing methods and concepts of measuring membrane reorganization dynamics on the same timescale as signaling events. This requires a full understanding of the spatial and temporal complexity of cell membranes, which include concepts of signaling microdomains, membrane rafts and lipid shells. We are currently focused on cell signaling events that are induced by virus-host cell interactions and ligands for receptors such as integrins and GPCRs.
Membrane rafts, cell signaling, adhesion and viral-host cell interactions. Our mechanistic studies of viral-host cell interactions, attempt to address the central hypothesis that the bidirectional signaling of Rho family GTPases (Rac1, Cdc42, and RhoA) and integrins is required for selection of the correct entry and endocytic pathway to viral replication. Viruses are believed to enter and exit cells through rafts, taking advantage of signaling elements that are bundled in raft domains. Fluorescently labeled viruses are excellent probes for analyzing virus-host cell interactions by flow cytometry and live microscopy imaging. In collaboration with the Hjelle lab, our current work focuses on the use of UV-inactivated hantavirus particles to examine virus host cell interactions of BSL-3 viruses, using the broad array of research tools available in a BSL-2 laboratory. Our methods and concepts are applicable to multiple classes of enveloped viruses.
Development of HTS Platform for small molecule inhibitors of viral-host cell interactions. We have established a robust high throughput assay for the discovery of small molecule inhibitors of specific binding interactions between enveloped viruses and cognate cell entry receptors using HTS flow cytometry. We use TEM measurements, absorption and fluorescence spectroscopies to characteize virus particles in terms of size and measurement of discretely defined number of fluorophores/particle. Quantification of virus particles assures batch-to-batch consistency over time.