All eukaryotes relies on calcium ion (Ca2+) as a second messenger to respond to internal and external signals. Defects in Ca2+-based signaling cause numerous human diseases. Despite the importance and broad medical implications, Ca2+ signaling mechanisms remain unclear. The challenging question concerns how Ca2+ encodes specific information coming from different primary signals and translate them into distinct responses at cellular, organ, and organismal levels. Encoding and decoding the specificity of Ca2+ signals have thus remain a long- standing puzzle in the signal transduction field. The PI’s laboratory studies Ca2+ signaling mechanisms using a model plant (Arabidopsis). Discoveries in Arabidopsis have established new conceptual framework applicable to Ca2+ signaling mechanisms in all eukaryotes and set the stage for this application. The breakthrough in Ca2+- encoding mechanism in plant innate immunity has demonstrated that plants and animals both recognize bacterial pathogens by cell surface receptors, followed by Ca2+ second messenger that activates the immune responses, providing a unified paradigm in Ca2+-mediated defense signaling in eukaryotes. The guided pollen tube elongation resembles axon guidance and fungal hyphae growth in that all these polarized cell growth processes involve specific Ca2+ oscillations orchestrated by multiple Ca2+ channels and transporters. The discovery of a new family of Ca2+ channels in male-female recognition prior to fertilization reinforces a general paradigm that Ca2+ signaling is a common language in cell-cell communication during reproduction. In the next five years, PI’s research will expand beyond the current project to include several new directions. In addition to continuing the studies on cyclic nucleotide-gated channels (CNGCs) in the contexts of pollen tube growth and innate immunity in the current project, the new program will include research on the newly discovered Ca2+ channels in reproductive cell death of male and female cells, root mechano-sensing, and plant-fungal interactions. The overall goals are to identify the influx Ca2+ channels and efflux transporters that control the dynamic changes in cytosolic Ca2+ levels, uncover regulatory mechanisms how these Ca2+-transporting proteins are regulated by external cues, and piece together signaling pathways that couple signals to responses in specific physiological contexts. The general approach is to utilize genetic tools to identify genes responsible for each signaling pathway, followed by electrophysiology and cell biology procedures to reconstitute the pathway in a cellular context, completed with biochemical and structural methods to evaluate structure-function relationship of gene products and deduce mechanistic processes. Such combination of tools has been proved to be highly effective and successful in dissecting the molecular mechanisms for Ca2+-encoding in PI’s ongoing research. Completion of the project will reveal new Ca2+ encoding mechanisms, contributing to the conceptual framework of Ca2+ signaling, which is highly relevant to human health.

Calcium (Ca) is a ubiquitous second messenger in all eukaryotes ranging from budding yeast, plants, to human. Defects in Ca signaling cause numerous human diseases including Alzheimer’s disease, heart failure, metabolic diseases, immune disorders, neurodegenerative diseases, and cancer. Proposed research will contribute to the understanding of the basic conceptual framework of calcium signaling mechanisms highly relevant to human health.