Investigating the role played by calcium ions in the signal transduction pathways orchestrating embryonic development.
Calcium signaling is studied through the use of aequorins, a group of bioluminescent proteins. They can either be microinjected or transfected into cells, without disturbing function or development. The pattern of luminescence that is emitted by an aequorin-loaded cell, tissue or embryo, reveals changing patterns and levels of free calcium. Dr Miller is currently studying the role of calcium signaling in fertilization, segregation, cytokinesis, gastrulation and segmentation in zebrafish, and in neural induction in Xenopus. His work also focuses on exploring the calcium-sensitive target elements interacting with both intracellular and intercellular calcium signals – such as cytoskeletal components, morphogenic protein secretions, and localized developmental gene expression via calcium-sensitive transcription factors. A second area of interest is to elucidate the structures and mechanisms of activation of receptor-activated calcium channels in the plasma membrane of non-excitable animal cells. This is being done by targeting aequorins to specific compartments and locations within cells. A third area of research is the development of microscopy and image processing techniques required to collect and visualize ultra-low levels of photon emission from living cells and embryos.
Jamieson, L., Waters, A., Ho, K.E., Chan, H.Y.S., Hung, J.T., Webb, S.E., Chan, C.M., Shipley, A.M., Williamson, J.G., Beer, J., Angus, C., and Miller, A.L. (2020). Short-term regulation of blood/interstial fluid Ca2+ concentration by the scales of anadromous sea trout (Salmo trutta) during smoltification and migration. Journal of Fish Biology: doi:10.1111/jfb.14553
Gou, C., Webb, S.E., Chan, C.M., andMiller, A.L.(2020). TPC2-mediated Ca2+ signaling is required for axon extension in caudal primary neurons in zebrafish embryos. Journal of Cell Science: jcs.244780 doi: 10.1242/jcs.244780
Hung, J.T., Webb, S.E., Palumbo, C., Lesniak, A., Shipley, A.M., Rubinacci, A., Joseph G. Kunkel, J.G,and Miller, A.L. (2019). Assessing the ability of zebrafish scales to contribute to the short-term homeostatic regulation of [Ca2+] in the extracellular fluid during calcemic challenges. Fisheries Science org/10.1007/s12562-019-01353-9.
Kelu, J.J., Sarah Webb, S.E., Galione, , and Miller, A.L. (2019). Characterization of ADP-ribosyl cyclase 1-like (ARC1-like) activity and NAADP signaling during slow muscle cell development in zebrafish embryos. Developmental Biology 445: 211-225.
Webb, S.E., Kelu, J.J., and Miller, A.L. (2019). Role of Two-Pore Channels in Embryonic Development and Cellular Differentiation. Cold Spring Harbor Perspectives in Biology, Geert Bultynck, Martin D. Bootman, Michael J. Berridge, and Grace E. Stutzmann, CSH Press, doi: 10.1101/chsperspect.a035170