Assistant Professor of Biology
Lab office: Science & Engineering Hall 5370
The survival of any organism hinges on an ability to monitor its external environment. Animals rely on chemical signals from their environment to detect food sources, potential hosts, noxious compounds, reproductive partners and can enable them to choose between alternative developmental states. Throughout evolution, olfaction represents one of the major senses by which organisms assess their external chemical environment.
Organisms as diverse as humans and nematodes utilize the same basic machinery for olfactory perception. In the case of the free-living nematode, Caenorhabditis elegans, hundreds of chemoreceptor genes (~5% of C. elegans genome) are regulated and expressed in chemosensory neurons (Bargmann et al., 1993; Troemel et al., 1995; Sengupta et al., 1996; Robertson, 1998). Similarly in mammals and insects, hundreds of olfactory receptor genes have been identified which regulate the olfactory response (Buck & Axel, 1991; Voshall et al., 1999; Zhang & Firestein, 2002). However, in order to effectively shape behavior, neural circuits must integrate sensory information by collating input and placing this input in a context of previous or concurrent sensory information. The modification of behavior based on this type of sensory integration is termed behavioral plasticity.
Types of behavioral plasticity include sensitization, habituation and adaptation, and on account of the high degree of conservation between mammalian and invertebrate sensory systems, much insight into behavioral plasticity has been gained through the study of invertebrate models. The less-complex central nervous system of many invertebrates makes them attractive for the molecular and genetic analysis of neuronal plasticity. Research on invertebrate model systems such as Aplysia (Castellucci et al., 1970) has greatly accelerated our understanding of neuronal plasticity.
The O’Halloran lab uses Caenorhabditis elegans to understand the cellular and molecular mechanisms that shape sensory plasticity.
Calcium functions as a diverse signaling molecule in a variety of cell types through activation and conformational changes of proteins, as well as via modulation of cellular capacitance (Berridge et al. 2000; Berridge et al. 2003; Bootman et al. 2001). Neurotransmitter release, muscle contraction, apoptosis and lymphocyte activation are some of the many cellular processes mediated by calcium signaling, and accordingly strict balance of calcium levels must be maintained in order to prevent cellular dysfunction. Cells accomplish this primarily by extruding calcium through Plasma Membrane Ca2+ ATPase (PMCA) pumps and also by utilizing exchanger ion transporters. PMCA proteins are high affinity/low capacity pumps which maintain calcium homeostasis over sustained periods of time by removing one Ca2+ ion for every ATP hydrolyzed. Exchangers such as Na+/Ca2+ exchangers (NCX), Na+/Ca2+/K+ exchangers (NCKX) and calcium/cation exchangers (CCX) are low affinity/high capacity ion transporters that rapidly expel calcium ions (Lytton.2007; Nicoll et al. 2013; Philipson and Nicoll. 2000 Phillipson et al. 2002). The NCX, NCKX, and CCX families of exchangers comprise the three branches of the family of Na+/Ca2+ exchangers in animals (Cai and Lytton. 2004; Lytton. 2007).
The O’Halloran lab uses the model system Caenorhabditis elegans to learn more about the in vivo role of sodium/calcium exchangers in the nervous system.
Wang, D., O'Halloran, D. & Goodman, M.B. (2013). GCY-8, PDE-2 and NCS-1 are Critical Elements of the cGMP-dependent Thermotransduction Cascade in the AFD Neurons Responsible for C. elegans Thermotaxis. Journal of General Physiology, 142(4): 437- 449.
He, C. and O’Halloran, D.M. (2013). Nuclear PKG localization is regulated by Go alpha and is necessary in the AWB neurons to mediate avoidance in Caenorhabditis elegans. Neuroscience Letters, 553: 35 - 39.
Sharma, V., Sacca-Schaeffer, J., Martin-Herranz, D., He, C., Brzozowski, E., Mendelowitz, Z., Fitzpatrick, D.A. & O’Halloran, D.M. (2013). Insight into the family of Na+/Ca2+ exchangers of Caenorhabditis elegans. Genetics, 195(2): 611 - 619.
Wojtyniak, M., Brear, A., O’Halloran, D.M. & Sengupta, P. (2013). Cell- and subunit-specific mechanisms of CNG channel ciliary targeting and localization in C. elegans. Journal of Cell Science, 126(19): 4381 - 4395.
O’Halloran, D.M. (2013). A Practical Guide to Phylogenetics for non-experts. J. Vis. Exp. In Press.
Smith, H., Linjiao, L., O’Halloran, D., Dagang, G., Xin-Yun, H., Samuel. A.D.T. & Hobert, O. (2013). Defining specificity determinants of cyclic GMP-mediated gustatory sensory transduction in Caenorhabditis elegans. Genetics. 194(4): 885 - 901.
He, C., Fitzpatrick, D.A. & O’Halloran, D.M. (2013). A comparative study into the molecular evolution of conserved signaling pathway members across olfactory, gustatory, and photo-sensory modalities. Journal of Genetics. 92(2): 327 - 334.
Fitzpatrick, D.A. & O’Halloran, D.M. (2012). Investigating the relationship between topology and evolution in a dynamic nematode odor genetic network. Int J Evol Biol. (12) 548081: 1 - 8.
He, C., Lee, J.I., L’Etoile, N.D. & O’Halloran, D.M. (2012). A Molecular Readout of Long-Term Olfactory Adaptation in C. elegans. J. Vis. Exp. (70) 4443.
Fitzpatrick, D. A. & O’Halloran, D.M. (2012). Frequency distribution of C. elegans and P. pacificus orthologs as a function of divergence. FigShare.
O’Halloran, D.M., Hamilton, O.S., Lee, J.I., Gallegos, M. & L’Etoile, N.D. (2012). Changes in cGMP levels affect the localization of EGL-4 in AWC in Caenorhabditis elegans. PLoS ONE. 7(2): e31614.
Lee, J.I.*, O’Halloran, D.M.*, Eastham-Anderson, J., Juang, B., Kaye, J.A., Hamilton, O.S., Lesch, B., Goga, A. & L’Etoile, N.D. (2010). Nuclear entry of a cGMP-dependent kinase converts transient into long-lasting olfactory adaptation. Proceedings of the National Academy of Sciences, 103 (13): 6016 - 6021 (*joint 1st authors). This research was featured here: The Persistent Smell in the Nucleus (2010). Science Signaling Vol. 3, Issue 117, p. ec110.
O’Halloran, D.M., Altshuler-Keylin, S., Lee, J.I. & L’Etoile, N.D. (2009). Regulators of AWC mediated olfactory plasticity in Caenorhabditis elegans. PLoS Genetics. 5(12): e1000761.
O'Halloran, D.M. & L’Etoile, N.D. (2007). Olfactory adaptation behavior in Caenorhabditis elegans. Korean Journal of Genetics, 29(2): 107 - 114.
Fitzpatrick*, D.A., O’Halloran, D.M*. & Burnell, A.M. (2006). Multiple Lineage Specific Expansions within the Guanylyl Cyclase Gene Family. BMC Evolutionary Biology, 6: 26: 1 - 18 (*joint 1st authors). Designated “Highly Accessed” on the BMC website.
O’Halloran, D.M., Fitzpatrick, D.A., Mc Inerney, J. O., Mc Cormack, G. P. & Burnell, A.M. (2006). The molecular phylogeny of a nematode specific clade of heterotrimeric G-protein subunit genes. Journal of Molecular Evolution, 63: 87 - 94.
O’Halloran, D.M., Fitzpatrick, D.A. & Burnell, A.M. (2006). The chemosensory system of Caenorhabditis elegans and other nematodes. In: Chemical ecology: from genes to ecosystems. Editors: L.M. Schoonhoven, J.J.A. Van Loon & M. Dicke. Springer press, 71 - 88. March 2006. ISBN: 1 - 40204783 - 5.
O’Halloran, D.M., Cafferkey, M.T. (2005). Multiplex PCR for identification of seven Streptococcus pneumoniae serotypes targeted by a 7-valent conjugate vaccine. Journal of Clinical Microbiology, 43(7): 3487 - 3490.
Burnell, A.M. & O’Halloran, D.M. (2003). Chemoreceptor genes: what can we learn from Caenorhabditis elegans and how we can apply this information to studies on other nematodes? Nematology Monographs & Perspectives, 2: 1 - 8.
O’Halloran, D.M. & Burnell, A.M. (2003). An investigation of chemotaxis in the insect parasitic nematode, Heterorhabditis bacteriophora. Parasitology, 127: 375 - 385.