David B. Morton, Ph.D.
Professor and Associate Dean for Research
The majority of the research projects in my laboratory focus on understanding molecular and cellular signaling pathways in the nervous system using the fruit fly Drosophila melanogaster as a model system. The unparalleled array of genetic tools that are available in Drosophila make it an invaluable system for unraveling the molecular and cellular basis of normal functioning of the human brain and the underlying mechanisms of disease. Three primary projects are currently ongoing in the lab:
Cyclic GMP signaling and neuronal hypoxia sensing
All animals require oxygen to survive and it is critical for an organism to be able to respond rapidly and appropriately to hypoxic conditions. My lab has been studying the function and regulation of the intracellular messenger, cyclic GMP (cGMP) for over 30yrs and we identified a novel class of guanylyl cyclases, the enzymes that synthesize cGMP, which are regulated by changes in oxygen levels. In Drosophila these enzymes are located throughout the nervous system, and in particular in sensory neurons, where they function as neuronal hypoxia detectors. When these neurons are activated in hypoxic conditions they signal to the CNS to initiate behavioral escape responses.
Molecular and cellular basis for Lou Gehrig's disease
Amyotrophic lateral sclerosis (ALS) or Lou Gehrig's disease is a relentlessly progressive neurodegenerative disease that in most cases leads to death 3-5 years after diagnosis. ALS is caused by the selective degeneration of motor neurons, which in ALS patients contain cytoplasmic protein aggregates containing an RNA-binding protein named TDP-43. We are utilizing the genetic tool kit available in Drosophila to understand the molecular and cellular outcomes of TDP-43 dysfunction that lead to neurodegeneration.
Methamphetamine action on the nervous systemMethamphetamine use is one of the top drug problems in America and is a significant contributor to crime in the United States. We have recently started to use Drosophila to help identify new targets that modulate the action of methamphetamine in the nervous system. We have now shown that the small GTPase, Rab10 modulates the effects of methamphetamine in flies. Future experiments will focus on determining which neurons require Rab10 expression and the function of Rab10 in methamphetamine action.
Recent Representative PublicationsVermehren-Schmaedick, A. Ainsley, J.A., Johnson, W.A., Davies, S-A. and Morton, D.B. (2010). Behavioral responses to hypoxia in Drosophila larvae are mediated by atypical soluble guanylyl cyclases. Genetics 186: 183–196.
Vermehren-Schmaedick, A., Scudder, C., Timmermans, W. and Morton, D.B. (2011). Drosophila gustatory preference behaviors require the atypical soluble guanylyl cyclases. J. Comp Physiol A. 197, 717-727.
Hazelett, D.J., Chang, J-C., Lakeland, D.L. and Morton, D.B. (2012). Comparison of parallel hi-throughput RNA-sequencing between knockout of TDP-43 and its overexpression reveals primarily non-reciprocal and non-overlapping gene expression changes in the central nervous system of Drosophila. G3:Genes, Genomes, Genetics 2, 789-802.
Brown, K.M., Day, J.P., Huston, E., Zimmermann, B., Hampel, K., Christian, F., Romano, D., Terhzaz, S., Lee, L.C.Y., Willis, M.J., Morton, D.B., Beavo, J.A., Shimizu-Albergine, M., Davies, S.A., Kolch, W., Houslay, M.D. and Baillie, G.S. (2013). Phosphodiesterase-8A binds to and regulates Raf-1 kinase. Proc. Natl. Acad. Sci. 110, E1533-42.
Chang, J-C, Hazelett, D.J., Stewart, J.A. and Morton, D.B. (2014). Motor neuron expression of the voltage-gated calcium channel cacophony restores locomotion defects in a Drosophila, TDP-43 loss of function model of ALS. Brain Res. 1584, 39-51.
Vanderwerf, S.M., Buck, D.C., Wilmarth, P.A., David, L.L., Sears, L.M., Morton, D.B. and Neve, K.A. (2015). Role for Rab10 in methamphetamine-induced behavior. PloS One DOI:10.1371/journal.pone.0136167.