Our interests lie in the area of cell signaling, i.e., the ways in which excitable cells in the nervous system communicate with each other as well as within themselves. Specific topics include the mechanisms of neurotransmitter release, the interaction of neurotransmitters with their receptors, and the role of intracellular messengers in linking receptor binding to the final cellular response.
Calcium ions play an ubiquitous role in cells of the body as intracellular messengers, being implicated in phenomena as diverse as egg fertilization, muscle contraction, neurotransmission, and learning and memory. To study these processes we have developed optical techniques for stimulating intracellular messenger pathways and for recording the resulting changes in intracellular free calcium. Photolabile “caged” compounds, such as caged inositol trisphosphate can be loaded into cells and then be induced to release a precisely controlled amount of free messenger by stimulation with a flash of ultraviolet light. Calcium that is liberated from intracellular stores by the photo released inositol trisphosphate can then be recorded using laser confocal and two-photon imaging of fluorescence signals from long wavelength calcium indicator dyes.
Projects presently underway in the lab include:
1. Investigation of the mechanisms underlying the generations of “elementary” calcium signals, and their roles in generating global cellular calcium signals
2. Multi-scale modeling of cellular calcium signaling, from single channels to whole cell. (Collaboration with Dr. John Pearson, LANL; Kevin Foskett and Daniel Mak, U. Penn; Jianwei Shuai, Xiamen U., China).
3. Functional imaging of the immune system. Two-photon imaging of motility and calcium signaling in lymphocytes and antigen presenting cells within intact lymph nodes. (Collaboration with Dr. Mike Cahalan, UCI).
4. Development of optical imaging systems - most recently a multi-laser total-internal reflection microscope for nano-scale resolution of calcium signals and photoswitchable proteins.
For more detailed information on specific topics, please click on the links.