Auburn University | 1991 | Master of Science
Auburn University | 1988 | B.S.
Assistant Professor
Glendale, AZ
My lab is interested in the molecular mechanisms that regulate egg activation at fertilization. Sperm-egg fusion initiates a transient increase in the concentration of cytoplasmic calcium in the egg. This increase is a fundamental process that occurs in the eggs of all the organisms that have been studied (even plants) and it is critical for activating the egg to begin development. Incredibly, the molecular mechanism that links the sperm-egg interaction to the initiation of this calcium increase is only now beginning to be understood.
Our research focuses on the role of a particular enzyme called phospholipase C gamma. PLC-gamma is a member of a larger class of cytoplasmic enzymes called phospholipases. These enzymes function to produce two signaling messenger molecules called diacylglycerol and inositol 1,4,5-trisphosphate from membrane phospholipids. They function in many cell types, including nerves, muscles and immune cells. In eggs, PLC-gamma is the enzyme that is necessary for the calcium release from the endoplasmic reticulum that is needed for egg activation. With colleagues, we have identified two Src tyrosine kinases that interact with PLC-gamma and are also needed at fertilization. This has led to us to propose the following signaling pathway in our model systems (sea urchins, starfish, ascidians, and maybe frogs!).
Title
Assistant Professor
Campus
Glendale, AZ
College
College of Graduate Studies - AZ
Department
Biochemistry and Molecular Genetics
Program
Biomedical Sciences (M.A.)
Biomedical Sciences (M.B.S.)
Osteopathic Medicine
Using a combination of biochemistry, molecular biology and live-cell microscopy, we have discovered that PLC-gamma is required for the initiation of the calcium increase during fertilization in starfish and sea urchin eggs. In collaboration with Dr. Kathy Foltz of the University of California at Santa Barbara and Dr. Laurinda Jaffe of the University of Connecticut Health Center, we have cloned a starfish PLC-gamma cDNA from an arrayed oocyte cDNA library. We are currently using this clone as a tool to look for proteins that interact with PLC-gamma in a fertilization-specific manner. We have determined that there are many tyrosine-phosphorylated proteins, some from the sperm and some from the egg, that bind to PLC-gamma only after fertilization. The identification of these proteins is a major goal of the laboratory in the coming years. Two graduate students from the laboratory (Leia Shuhaibar and Lu Zhong) have also developed a method for the visualization of changes in an enzyme called Mitogen-activated Protein Kinase (MAPK) using single cells. This allows us to gain a better understanding of the regulation of this enzyme during oocyte maturation and fertilization. Ph.D. students Lauren Bates and Emily Wiseman (now Dr. Wiseman) have developed a new starfish egg transcriptome which will allow us to identify and clone any proteins identified in our screens for novel signaling molecules at fertilization. The transcriptome can be accessed here: https://www.ncbi.nlm.nih.gov/bioproject/?term=PRJNA398668
Wiseman, E., Bates, L, and Carroll, DJ. (2021) Recovery of Sea Star Egg Cell Surface Proteins Released at Fertilization. Methods Mol. Biol. Vol 2219, 151-161.
Bates L, Wiseman E, Kitson, J., Carroll DJ. (2021) Identification of SH2 domain-mediated Protein Interactions that Operate at Fertilization in the Sea Star Patiria miniata. Methods Mol. Biol. Vol 2219, 119-135.
Bates, L., Wiseman, E., and Carroll, D.J. (2019) Analyzing gene expression in sea star eggs and embryos using bioinformatics. Methods Cell Biol., 150:471-483.
Shuhaibar, L., Carroll, D.J., and Jaffe, L.A. (2018) "Preparing for Fertilization: Intercellular Signals for Oocyte Maturation" in Diversity in Mechanisms of Fertilization. Yasuhiro Iwao, Editor, Zoological Society of Japan.
Wiseman, E., Bates, L., Dubé, A., and Carroll, D.J. (2018) Starfish as a Model System for Analyzing Signal Transduction during Fertilization. Results Probl Cell Differ. 65, 49-67.
Bates, L.S., Wiseman, E., and Carroll, D.J. (2018) “Patiria minita: transcriptome shotgun assembly”, Bioproject PRJNA398668. National Library of Medicine (US), National Center for Biotechnology Information; 2018 Jan.