My lab investigates the molecular basis by which neural circuits integrate sensory input to drive appropriate behavioral programs. Our research has covered gustatory and thermosensory circuits in C. elegans but our main focus examines olfactory circuitry. Previous work identified a protein kinase G (PKG) called EGL-4 that is necessary for short and long-term olfactory adaptation in C. elegans. It has also been shown that transient nuclear localization of EGL-4 in the AWC neuron facilitates adaptation after sustained odor input, and my lab has shown that constitutively nuclear EGL-4 is required in the AWB neurons (another pair of olfactory neurons) for the detection of repellent odors. In terms of short-term adaptation my lab has shown that cyclic nucleotide gated (CNG) channels play a central role in driving this behavior. CNG channels are non-selective cation channels that are gated by direct binding of cGMP or cAMP. From our research we found that the CNG channel subunit, CNG-3, is necessary for short-term adaptation in the AWC and in a separate study, my lab also found that the CNG subunit, CNG-1, is required to promote cross adaptation responses between distinct olfactory cues.
My lab also studies the sensory neurobiology of parasitic nematodes. This is a collaboration with Drs. Eleftherianos (Biology) and Hawdon (MITM). Here we are attempting to understand the host factors which are sensed by a parasitic nematode (PN) that initiate the infection process. The developmentally arrested dauer stage of C. elegans is analogous to the infective stage of many important parasites, and recovery from dauer has been used as a model for resumption of development during infection. The availability of powerful molecular and genetic tools makes it a useful surrogate for studying PN infection. However, C. elegans is not a parasite, and the dauer stage is facultative and not obligatory as in PNs. Therefore, a parasitic equivalent of C. elegans would allow more relevant investigations into PN infection and development. The insect parasite Heterorhabditis bacteriophora offers great potential as such a model. With its endosymbiotic Photorhabdus luminescens bacteria, Heterorhabditis bacteriophora invades multiple insect species, which it kills and exploits as a food source for the development of several nematode generations. When the insect cadaver is exhausted, infective (dauer) juveniles (IJ) exit and seek a new host to infect. The obligatory dauer infective stage suggests Heterorhabditis bacteriophora is a more representative model of PN infection than C. elegans, and the ability to culture the life cycle on plates will allow studies of the molecular events occurring during infection of the host that are inaccessible using vertebrate hosts. Insect models, like Drosophila melanogaster, have served as outstanding organisms in biomedical research for identifying novel molecular mechanisms of the innate immune response to pathogenic infection. The Drosophila-Heterorhabditis system is considered an ideal model to investigate simultaneously the molecular basis of PN pathogenicity and host immune function. We are using this system to study the infection process as well as developing novel drugs for resistance.
My lab has begun studying the mechanisms through which neural circuits develop using C. elegans. To get a molecular foothold into the problem of circuit development, we began looking into the family of sodium calcium exchangers (NCX). From our research, my lab has found a link between calcium homeostasis via NCX and circuit patterning. NCX have been implicated in diverse neurological diseases such as Alzheimer’s, amyotrophic lateral sclerosis (ALS), Parkinson’s, and autism, and my hope is that my lab’s data may be able to provide critical insight linking circuit structure to disease.
Sharma, V., Roy, S., Sekler, I. & O’Halloran, D.M. (2017). The NCLX-type Na+/Ca2+ exchanger NCX-9 is required for patterning of neural circuits in Caenorhabditis elegans. Journal of Biological Chemistry, 292(13): 5364–5377. PMID: 28196860
O’Halloran, D.M. (2017). phylo-node: A Molecular Phylogenetic Toolkit using Node.js. PLoS ONE. In Press.
O’Halloran, D.M., Altshuler-Keylin, S., Zhang, X., He, C., Morales-Phan, C., Yu, Y., Brueggeman, C., Kaye, J., Chen, T-Y. & L’Etoile, N.D. (2017). Contribution of the cyclic nucleotide gated channel subunit, CNG-3, to olfactory plasticity in Caenorhabditis elegans. Nature Scientific Reports, 7(1):169. PMID: 28279024
O’Halloran, D.M., Uriagereka-Herburger, I. & Bode, K. (2017). STITCHER 2.0: primer design for overlapping PCR applications. Nature Scientific Reports, 7:45349. PMID: 28358011.
Vadnal, J., Ratnappen, R., Keaney, M., Kenney, E., Eleftherianos, I., O’Halloran, D.M. & Hawdon, J. (2017). Identification of candidate infection genes from the model entomopathogenic nematode Heterorhabditis bacteriophora. BMC Genomics, 18(1):8. PMID: 28049427
He, C., Altshuler-Keylin, S., Daniel. D., L’Etoile, N.D. & O’Halloran, D.M. (2016). The cyclic nucleotide gated channel subunit CNG-1 instructs behavioral outputs in Caenorhabditis elegans by coincidence detection of nutritional status and olfactory input. Neuroscience Letters, 632:71-78. PMID: 27561605
O’Halloran, D.M. (2016). NemaCount: quantification of nematode chemotaxis behavior in a browser. Invertebrate Neuroscience, 16(2):5. PMID: 27209025
Ratnappen, R., Vadnal, J., Kenny, M., Eleftherianos, I., O’Halloran, D.M. & Hawdon, J. (2016). RNAi-mediated gene knockdown by microinjection in the model entomopathogenic nematode Heterorhabditis bacteriophora. Parasites and Vectors, 18;9(1):160. PMID: 26993791
Sharma, V. & O’Halloran, D.M. (2016). Nematode sodium calcium exchangers: a surprising lack of transport. Bioinformatics and Biology Insights. 10:1-4. PMID: 26848260
O’Halloran, D.M. (2016). PrimerMapper: high throughput primer design and graphical assembly for PCR and SNP detection. Nature Scientific Reports, 6:20631. PMID: 26853558
O'Halloran, D.M. (2015). STITCHER: a web resource for high-throughput design of primers for overlapping PCR applications. Biotechniques, 58(6): 325-328.
He, C. and O'Halloran, D.M. (2014). Analysis of the Na+/Ca2+ exchanger gene family within the phylum Nematoda. PLoS ONE, 9(11): e112841.
Sharma, V. and O'Halloran, D.M. (2014). Recent structural and functional insights into the family of sodium calcium exchangers. genesis The Journal of Genetics and Development. 52 (2): 93 - 109.
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. (84) 50975. PMID: 24562012.
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.
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.
BISC 2220 - Developmental Neurobiology
BISC 2320 - Neural Circuits and Behavior
BISC 4180 - Undergraduate Research Seminar