Cell & Neurobiology
Zilkha Neurogenetic Institute
Keck School of Medicine
- Membranes & Transport
- Cellular Neurobiology
- Microbial/Invertebrate Genetics
Research OverviewIntercellular signaling in the brain occurs at highly specialized subcellular structures called synapses. Synapses are surprisingly diverse in their structural and functional properties. For example, different synapses in the brain vary significantly in size, the number of neurotransmitter release sites, the pool of synaptic vesicles available for release and the probability of vesicle release. Beyond this diversity between synapses, the properties of each synapse are highly dynamic. This plasticity in synaptic properties is thought to underlie the specificity of neuronal wiring during development, and processes such as learning and memory. Synapses are biochemically complex structures composed of hundreds of different proteins. However, very little is known about the changes in molecular composition and signal transduction properties that underlie the diversity of synaptic function.
The Sieburth lab combines behavioral, genetic, RNA interference, and live imaging techniques to dissect synaptic function at a systems and molecular level in C. elegans. We use C. elegans as a model organism for studying synaptic biology, because of its simple neuronal circuitry, the ability to visualize synapses by fluorescent imaging in live animals, and its powerful genetics. We are focusing on conducting a detailed analysis of several genes that are candidates for being essential regulators of the synaptic vesicle cycle. We are also interested in how synaptic activity affects the overall structural organization of a synapse by imaging GFP tagged proteins in live animals under a variety of different conditions that alter synaptic transmission.
- Web Site:
- Sieburth lab website
- Mailing Address:
- 2821 HSC
- Office Location:
- ZNI 327
- Office Phone:
- (323) 442-2013
- Lab Location:
- ZNI 321
- Ph.D. University of Colorado
- Postdoctoral research: Massachusetts General Hospital, Harvard Medical School
Wang H, Girskis K, Janssen T, Dasgupta K, Knowles JA, Schoofs L, and Sieburth D. Neuropeptide Secretion Couples a Pacemaker to a Rhythmic Behavior. (In revision).
Staab T, Griffin T, Corcoran C, Evgrafov O, Knowles JA, and Sieburth D. The Conserved SKN-1/Nrf2 Stress Response Pathway Regulates Synaptic Function in Caenorhabditis elegans. (In review).
Pickering A, Staab TA, Tower JG, Sieburth D, Davies KJ. A Conserved Role for the 20S Proteasome and Nrf2 Transcription Factor in Oxidative-Stress Adaptation in Mammals, C. elegans and D. melanogaster. Journal of Experimental Biology. 2102 (In Press).
Chan JP and Sieburth D. Localized sphingolipid signaling at presynaptic terminals is regulated by calcium influx and promotes recruitment of priming factors. Journal of Neuroscience. 2012 (In Press).
Chan JP, Hu Z, and Sieburth D. Recruitment of sphingosine kinase to presynaptic terminals by a conserved muscarinic signaling pathway promotes neurotransmitter release. Genes Dev. 2012 May 15;26(10):1070-85. -PubMed
Hao Y, Hu Z, Sieburth D, and Kaplan JM. RIC-7 promotes neuropeptide secretion. PLoS Genetics. 2012 Jan;8(1):e1002464.
Bedrood S,Jayasinghe S,Sieburth D,Chen M,Erbel S,Butler PC,Langen R,Ritzel RA - Annexin A5 directly interacts with amyloidogenic proteins and reduces their toxicity. - Biochemistry  Nov 10;48(44):10568-76 -Link
Vashlishan AB, Madison JM, Dybbs M, Bai J, Sieburth D, Ch'ng Q, Tavazoie M, Kaplan JM. (2008) An RNAi screen identifies genes that regulate GABA synapses. Neuron. 58(3):346-361. -PubMed
Sieburth D, Madison, JM and Kaplan, JM. (2007) PKC-1 regulates secretion of neuropeptides. Nature Neuroscience. 10(1): 49-57. -PubMed
Ch'ng Q,Sieburth D,Kaplan JM - Profiling synaptic proteins identifies regulators of insulin secretion and lifespan. - PLoS Genet  Nov;4(11):e1000283 -Link
Sieburth D, Ch'ng Q, Dybbs M, Tavazoie M, Kennedy S, Wang D, Dupuy D, Rual JF, Hill DE, Vidal M, Ruvkun G, Kaplan JM. (2005) Systematic analysis of genes required for synapse structure and function. Nature. 436(7050):510-7. -PubMed