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.
Kelu, J.J., Webb, S.E., Galione, A. and Miller, A.L. (2018). TPC2-mediated Ca2+ signaling is required for the established of synchronized connectivity within the developing zebrafish spinal circuitry. Develeopmental Biology 438: 57-68
Kelu, J.J., Webb, S.E., Parrington, J., Galione, A., and Miller, A.L. (2017). Calcium release via two-pore channel type-2 (TPC2) is required for slow muscle cell fibrillogenesis and myotomal patterning in intact zebrafish embryos. Developmental Biology 425: 109-129.
Webb, S.E., and Miller, A.L. (2013). Calcium signalling in extra-embryonic domains during early teleost development. International Review of Cell and Molecular Biology 304: 369-418.
Webb, S.E., and Miller, A.L. (2003). Calcium signaling during embryonic development. Nature Reviews Molecular Cell Biology 4: 539-551.
Cubitt, A.B., Firtel, R.A., Fischer, G., Jaffe, L.F., Karplus, E., and Miller, A.L. (1995). Patterns of free calcium in developing Dictyostelium. Development 121: 2291-2301.