Tom O’Halloran received his Bachelor’s and Master’s degrees in Chemistry from the University of Missouri. He went on to receive his PhD degree in Bioinorganic Chemistry from Columbia University, New York, where he studied the coordination chemistries and reactivities of platinum complexes related to the anti-cancer drug cisplatin. He is currently an MSU Foundation Professor in the Department of Microbiology & Molecular Genetics and the Department of Chemistry and the Director of the Elemental Health Institute. Previously, he was the Morrison Professor in the Department of Chemistry and the Department of Molecular Biosciences at Northwestern University and Founding Director of the Chemistry of Life Processes Institute.
The O’Halloran laboratory focuses on developing a quantitative understanding of the regulatory roles of transition metals in controlling cellular physiology. Each cell must acquire millions (bacteria) to billions (eukaryotes) of metal ions, monitor, and balance the levels of these ions to prevent excessive accumulation while simultaneously keeping metals flowing into essential catalytic and signaling processes. Using our new zinc-specific probes and synchrotron X-ray fluorescence microscopy, we developed novel imaging methods to discover that zinc fluxes in the mammalian egg regulate both the exit from the meiotic cell cycle and the resumption of mitosis upon fertilization. Most strikingly, fertilization of a mammalian egg initiates a series of ‘zinc sparks’, rapid exocytosis of over 10 billion zinc ions, that are necessary to induce the egg-to-embryo transition. Very recently, we have discovered that zinc sparks are not only conserved in the amphibian Xenopus laevis, but fertilization also triggers a loss of intracellular manganese to prevent polyspermy.
Metal fluxes controlling fertilization. Left: live-cell fluorescence zinc imaging demonstrates that fertilization of X. laevis oocytes induces a zinc spark, which was first observed in mammalian models (Seeler et al., Nat. Chem. 2021). Middle and Right: to quantify and map labile pools of metals, our lab develops metal-responsive probes, such as the ZincBY family of zinc-responsive fluorescent probes (Garwin et al. J. Am. Chem. Soc. 2019).
Quantitative Imaging Approaches to Understanding Biological Processing of Metal Ions. Zee, D. Z.; MacRenaris, K. W.; O’Halloran, T. V. Curr. Opin. Chem. Biol. 2022.
Dynamic Zinc Fluxes Regulate Meiotic Progression in Caenorhabditis elegans. Mendoza, A.D.; Sue, A; Antipova, O; Vogt, S; Woodruff, T.K.; Wignall, S.M.; O’Halloran, T.V. Biol. Reprod. 2022.
Metal Ion Fluxes Controlling Amphibian Fertilization. Seeler, J. F.; Sharma, A.; Zaluzec, N. J.; Bleher, R.; Lai, B.; Schultz, E. G.; Hoffman, B. M.; LaBonne, C.; Woodruff, T. K.; O’Halloran, T. V. Nat. Chem. 2021, 13, 683–691.
Interrogating Intracellular Zinc Chemistry with a Long Stokes Shift Zinc Probe ZincBY-4. Garwin, S. A.; Kelley, M. S. J.; Sue, A. C.; Que, E. L.; Schatz, G. C.; Woodruff, T. K.; O’Halloran, T. V. J. Am. Chem. Soc. 2019, 141, 16696–16705.
Quantitative Mapping of Zinc Fluxes in the Mammalian Egg Reveals the Origin of Fertilization-Induced Zinc Sparks. Que, E. L.; Bleher, R.; Duncan, F. E.; Kong, B. Y.; Gleber, S. C.; Vogt, S.; Chen, S.; Garwin, S. A.; Bayer, A. R.; Dravid, V. P.; Woodruff, T. K.; O’Halloran, T. V. Nat. Chem. 2015, 7, 130–139.
Department of Microbiology & Molecular Genetics
3007 Interdisciplinary Science & Technology Building
Michigan State University
East Lansing, Mi 48824