Molecular mechanisms and neuronal circuitry underlying regulation of sleep
There are two major directions to my lab's research. (1) We study the mechanisms that control the sleep/wake cycle in the model organism Drosophila melanogaster. We use genetic, cell biological, biochemical and molecular biological techniques to identify and manipulate behaviorally relevant genes and neural circuits. We also employ electrophysiological techniques to study neuronal excitability. Our studies have implicated several genes in sleep regulation, including endogenous toxin-like molecules called Ly6 proteins, which we have shown to regulate excitability and synaptic transmission. My lab has also developed a novel assay for studying sleep homeostasis, a mysterious process that is intimately tied to the biological needs fulfilled by sleep, which are unknown. Our studies are defining the neural circuitry and molecular mechanisms underlying sleep homeostasis with the ultimate goals of identifying the biological basis of sleep need and targets for intervening in sleep-related disorders. (2) We also study the function of mammalian Ly6 proteins. Our data indicate that these proteins form complexes with and modulate the functions of several classes of pharmacologically important membrane signaling proteins with implications for both nicotine addiction and Alzheimer's Disease. Ongoing projects in my lab include determining (a) the cellular functions of newly identified sleep-regulating genes in flies and (b) the mechanisms and consequences of ion channel/receptor modulation by mammalian Ly6 proteins.
Joiner, W.J. Unraveling the evolutionary determinants of sleep. Curr Biol. 26, R1073–R1087, 2016.
Robinson, J.E., Paluch, J., Dickman, D.K., and Joiner, W.J. ADAR-mediated RNA editing suppresses sleep by acting as a brake on glutamatergic synaptic plasticity.
Nat Commun. 7:10512, 2016.
Seidner, G.A., Robinson, J.E., Wu, M., Worden, K., Masek, P., Roberts, S.W., Keene, A.C., and Joiner, W.J. Identification of neurons with a privileged role in sleep homeostasis in Drosophila melanogaster. Curr Biol. 25, 2928-2938, 2015.
Wu, M., Puddifoot, C.A., Taylor, P., and Joiner, W.J. Mechanisms of Inhibition and Potentiation of α4β2 Nicotinic Acetylcholine Receptors by Members of the Ly6 Protein Family. J. Biol. Chem. 290, 24509-18, 2015.
Puddifoot, C.A., Wu, M., Sung, R.J., and Joiner, W.J. Ly6h Regulates Trafficking of Alpha7 Nicotinic Acetylcholine Receptors and Nicotine-Induced Potentiation of Glutamatergic Signaling. J. Neurosci. 35, 3420-30, 2015.
Wu, M., Robinson, J.E., and Joiner, W.J. SLEEPLESS is a bi-functional regulator of excitability and cholinergic synaptic transmission. Curr Biol. 24, 621-9, 2014.