The Hays’ laboratory is applying genetic, molecular and biochemical approaches in Drosophila to study the molecular regulation of motor proteins and intercellular transport.
Mitotic mechanisms: Our mutational analysis of the Drosophila dynein motor protein revealed its essential function in mitotic cell divisions within living embryos. We are testing the hypothesis that phosphorylation of dynein regulates the stripping of checkpoint proteins from kinetochores and mitotic progression. To analyze the functional signficance of identified phosphorylation sites, target residues are systematically mutated and mutant transgenes expressed in vivo.
Neuronal transport: The extended morphology of axons and dendrites makes post-mitotic neurons especially dependent on polarized transport, and ideal for studying the regulation of transport.In neurons, motor proteins transport critical signals over long distances to regulate neuronal survival and cell death, as well as to trigger the onset of neurodegenerative disease or neuronal regeneration. Our recent efforts are directed at studying neuronal transport in Drosophila to ask whether disruption of transport is a convergence point in the development of neurodegenerative disease. We are pursuing the gene products and mechanisms that regulate motor proteins, and neuronal transport in Drosophila (fly) models of neurodegeneration.
Selected Publications: PubMed Search
Tubman E, He Y, Hays TS, Odde DJ. (2018) Kinesin-5 mediated chromosome congression in insect spindles. Cell Mol Bioeng. Feb;11(1):25-36.
Adam W. Avery, David. D. Thomas, Thomas. S. Hays. (2017) A β-III-spectrin spinocerebellar ataxia type 5 mutation reveals a dominant cytoskeletal mechanism that underlies dendritic arborization. Proc Natl Acad Sci U S A. 31;114(44): E9376-E9385.
Adam W. Avery, Michael E. Fealey, Fengbin Wang, Albina Orlova, Andrew Thompson, David D. Thomas, Thomas S. Hays, Edward H. Egelman. (2017) Structural basis for high-affinity actin binding revealed by a β-III-spectrin SCA5 missense mutation. Nature Communications 7;8(1):1350.
Amanda L. Neisch, Adam W. Avery, Min-gang Li, Thomas S. Hays. (2017) Drosophila cytoplasmic dynein: mutations, tools and developmental functions. In King, S.M., ed. Dyneins: Structure, Biology and Disease. 2nd edition.
Neisch AL, Neufeld TP, Hays TS. (2017) A STRIPAK complex mediates axonal transport of autophagosomes and dense core vesicles through PP2A regulation. J Cell Biol. Feb;216(2):441-461.
McIntosh JR, Hays T. (2016) A Brief History of Research on Mitotic Mechanisms. Biology (Basel). Dec 21;5(4). pii: E55.
Bhaban S, Materassi D, Li M, Hays T, Salapaka M. (2016) Interrogating Emergent Transport Properties for Molecular Motor Ensembles: A Semi-analytical Approach. PLoS Comput Biol. Nov 3;12(11):e1005152.
Mauvezin C, Neisch AL, Ayala CI, Kim J, Beltrame A, Braden CR, Gardner MK, Hays TS, Neufeld TP. (2016) Coordination of autophagosome-lysosome fusion and transport by a Klp98A-Rab14 complex in Drosophila. J Cell Sci. Mar 1;129(5):971-82.
Avery AW, Crain J, Thomas DD, Hays TS. (2016) A human B-III spectrin spinocerebellar ataxia type 5 mutation causes high-affinity F-actin binding. Sci Rep. Feb 17; 6:21375.
Neisch AL, Avery AW, Machamer JB, Li MG, Hays TS. (2016) Methods to identify and analyze gene products involved in neuronal intracellular transport using Drosophila. Methods Cell Biol.131:277-309.
Materassi, D., Roychowdhury, S., Hays, T., Salapaka, M. (2013) An exact approach for studying cargo transport by an ensemble of molecular motors. BMC Biophysics 6:14.
Smith RB, Machamer JB, Kim NC, Hays, TS, Marques G. (2012) Relay of retrograde synaptogenic signals through axonal transport of BMP receptors. J Cell Sci. 15:3752-64.
Reis GF, Yang G, Szpankowski L, Weaver C, Shah SB, Robinson JT, Hays TS, Danuser G, Goldstein LS. (2012) Molecular motor function in axonal transport in vivo probed by genetic and computational analysis in Drosophila. Mol. Biol. Cell. 23:1700-14.
Aggarwal, T., Materassi, D., Davison, R., Hays, T.S., and Salapaka, M. (2012) Detection of Steps in Single Molecule Data. Cellular and Molecular Bioengineering v.5(1):14-31.
Lorenzo D, Li M.-G, Mische, S., Armbrust, K, Ranum, L and Hays TS. (2010) Spectrin mutations that cause spinocerebellar ataxia type 5 impair axonal transport and induce neurodegeneration in Drosophila.J. Cell Biol. 189:143- 58. PMCID: PMC2854382.