CAREER: Single-molecule imaging of T cell recognition and signaling

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AbstractHuang; 1653782T-cells are a type of white blood cell that circulate around our bodies, scanning for cellular abnormalities and infections. The research goal is to understand the molecular mechanism of T cell recognition and signaling, which determines the selection, development, fate, and function of a T cell. Existing T-cell studies cannot directly visualize and measure the dynamic interactions and signaling events with enough spatiotemporal resolution. The PI proposes to use single-molecule resonance energy transfer and light-sheet microscopy to address this immunology problem by measuring early T cell intracellular signaling kinetics. The PI will integrate research within teaching and create a research-intensive learning environment to educate students at the interface of immunology and engineering through a new emerging discipline called immune-engineering. In addition, the PI will develop educational materials, demonstrations, and web tutorials to inspire students to explore new research areas, and develop novel technologies to drive the booming field of immune-engineering.The research project will use Forster's resonance energy transfer (FRET) to study molecular mechanisms of T cell recognition and signaling. The PI will attach fluorescent markers to the membrane receptors of T cells responsible for recognition and signaling. Furthermore, the PI will visualize T-cell receptor conformational changes, quantify the role of CD4, and measure early T-cell intracellular signaling kinetics in-situ. Also, he will observe T-cell receptor (TCR) and CD4 binding to peptide bound histocompatibility complexes. This initiates T-cell recognition and signaling at the cell membrane; antigen recognition will trigger proximal TCR signal transduction.