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August 01 - August 31

4 entries found

Unravelling..
Start date: August 15
11:00 am 12:00 pm

Description: 

Abstract:

"The main interests of our lab are the molecular mechanisms underlying metabolic disease, cancer and ageing. These morbidities have a profound impact, both medically and also social and economically. Animals typically live in close association with commensal and symbiotic microbes. Recent studies have revealed that the status of gut microbiota can influence nutrition-related syndromes. However, to-date we know very little about how such interactions are regulated. The suspected role of host-microbiota interactions in human disease and regulation of metabolism is largely derived from observational studies, and it is often difficult to establish whether changes in microbiota are cause or effect of pathology. Thus, it is important to understand how these microbial communities determine human physiology, and if they can be targeted by drugs to improve human health. Our lab utilises a complementary host model organism pipeline (mice and nematode worms) with the potential to unravel drug-diet-microbe-host interactions. In particular, we utilise two tractable genetic models: the bacterium E. coli and the nematode C. elegans and combine classical and advanced microbial genetics and high-throughput genomic/chemical approaches with targeted metabolomics at the holobiont level. Our work has identified drugable mechanisms in bacteria (e.g. signalling/biochemical pathways) that alter microbial metabolite availability with the capacity to regulate host processes and physiological outputs in the context of cancer and ageing."

5 most important publications:

1 Scott, T. A., et al., Typas, A., Greene, N. D. E. & Cabreiro, F. Host-Microbe Co-metabolism Dictates Cancer Drug Efficacy in C. elegans. Cell 169, 442-456 e418, doi:10.1016/j.cell.2017.03.040 (2017).

2 Norvaisas, P & Cabreiro F. Pharmacology in the age of the holobiont. Current opinion in systems Biology 10, 34-42, doi.org/10.1016/j.coisb.2018.05.006

3 Cabreiro, F. & Gems, D. Worms need microbes too: microbiota, health and aging in Caenorhabditis elegans. EMBO Mol Med 5, 1300-1310, doi:10.1002/emmm.201100972 (2013).

4 Cabreiro, F., et al., Greene, N. D. & Gems, D. Metformin retards aging in C. elegans by altering microbial folate and methionine metabolism. Cell 153, 228-239, doi:10.1016/j.cell.2013.02.035 (2013).

5 Cabreiro, F Burnett, C., Valentini, S et al., C., Partridge, L. & Gems, D. Absence of effects of Sir2 overexpression on lifespan in C. elegans and Drosophila. Nature 477, 482-485, doi:10.1038/nature10296 (2011).

Therapie vo..
Start date: August 22
10:00 am 11:30 am

Defining an..
Start date: August 30
09:30 am 10:30 am

Description: 

Abstract

Dendrite arbor topology determines the number, distribution and integration of neuron inputs, and neuron firing properties. Mature dendrite arbor pattern is the compound outcome of a series of branching events; with specific branches created early in dendrite outgrowth required to delineate the arbor into distinct main subtrees for arbor compartmentalization. We do not to understand the logic and molecular programs through which these fundamental topological patterning features of dendrites are defined. This is because in order to reveal this requires methods to simplifying the complexity of the differentiation process into discrete event units, and to identify which units generating specific features-an integrated approach spanning different spatiotemporal levels. Here, we reveal a specialized program underlying major branch formation show driven by a transient local upregulation of anterograde-directed microtubule nucleation at the dendrite tip. This process is separable from a continuous background of retrograde directed dendrite microtubule polymerization. By a genetic screen utilizing in vivo imaging coupled with automated dendrite feature detection and quantification, we identify the atypical myosin, Myo6, as a principal player in this process. Myo6 drives localized stabilization of single F-actin filaments at the tip, which in turn captures and target anterograde-directed microtubule polymerization events into discrete filopodia, driving tip-partition for major branch creation. Moreover we show differential use this process acts to control neuron type diversification. Overall, we reveal a tunable program that defines and diversifies critical major dendritic topological branch features that underlie circuit wiring and computation.

Selected Publications

Klebanow LR, Peshel EC, Schuster AT, De K, Sarvepalli K, Lemieux ME, Lenoir JJ, Moore AW, McDonald JA, and Longworth MS (2016). Drosophila Condensin II subunit, Chromosome Associated Protein-D3, regulates cell fate determination through non-cell autonomous signaling. Development. 143:2791-802.

Delandre C, Amikura R, Moore AW (2016). Microtubule Nucleation and Organization in Dendrites. Cell Cycle. 15:1685-92.

Yalgin C, Ebrahimi S, Delandre C, Yoong L F, Akimoto S, Tran H, Amikura R, Spokony R, Torben-Nielsen B, White KP, Moore AW (2015). Centrosomin represses dendrite branching by orienting microtubule nucleation. Nat Neurosci. 18:1437-45.

Chen YC, Auer-Grumbach M, Matsukawa S, Zitzelsberger M, Themistocleous AC, Strom TM, Samara C, Moore AW, Cho LT, Young GT, Weiss C, Schabhüttl M, Stucka R, Schmid AB, Parman Y, Graul-Neumann L, Heinritz W, Passarge E, Watson RM, Hertz JM, Moog U, Baumgartner M, Valente EM, Pereira D, Restrepo CM, Katona I, Dusl M, Stendel C, Wieland T, Stafford F, Reimann F, von Au K, Finke C, Willems PJ, Nahorski MS, Shaikh SS, Carvalho OP, Nicholas AK, Karbani G, McAleer MA, Cilio MR, McHugh JC, Murphy SM, Irvine AD, Jensen UB, Windhager R, Weis J, Bergmann C, Rautenstrauss B, Baets J, De Jonghe P, Reilly MM, Kropatsch R, Kurth I, Chrast R, Michiue T, Bennett DL, Woods CG, Senderek J (2015). Transcriptional regulator PRDM12 is essential for human pain perception. Nat Genet. 7:803-8.

Taniguchi H, Moore AW (2014). Chromatin regulators in neurodevelopment and disease: Analysis of fly neural circuits provides insights. Bioessays. 36:872-83.

Bard-Chapeau EA, Szumska D, Jacob B, Chua BQ, Chatterjee GC, Zhang Y, Ward JM, Urun F, Kinameri E, Vincent SD, Ahmed S, Bhattacharya S, Osato M, Perkins AS, Moore AW, Jenkins NA, Copeland NG (2014). Mice carrying a hypomorphic Evi1 allele are embryonic viable but exhibit severe congenital heart defects. PLoS One. 9:e89397.

Karim MR, Endo K, Moore AW, Taniguchi H. (2014) Whole mount immunolabeling of olfactory receptor neurons in the Drosophila antenna. J Vis Exp (87).

Artinger EL, Mishra BP, Zaffuto KM, Li BE, Chung EKY, Moore AW, Chen Y, Cheng C, and Ernst P (2013). MLL-dependent network sustains hematopoiesis. Proc Natl Acad Sci USA. 110:12000-5.

Endo K, Karim MR, Taniguchi H, Krejci A, Kinameri E, Siebert M, Ito K, Bray S, Moore AW (2012). Chromatin modification of Notch targets in olfactory receptor neuron diversification. Nat Neurosci. 15:224-33.

Hohenauer T, Moore AW (2012). The Prdm family: expanding roles in stem cells and development. Development. 139:2267-82.

Nagel J, Delandre C, Zhang Y, Förstner F, Moore AW, Tavosanis G (2012). Fascin controls neuronal class-specific dendrite arbor morphology. Development. 139:2999-3009.

Growing a b..
Start date: August 30
04:00 pm 05:00 pm

Description: 

Abstract:

The major goal of our work is to understand how the physiological activity of tissues and organs contributes to morphogenetic processes. Our broadest question is how hydrostatic fluid pressure functions in morphogenesis of the zebrafish gut, notochord and spine. We also investigate the role specialized intestinal cell populations in nutrient and antigen absorption and how this activity regulates whole organism physiology and development. Our approach combines forward and reverse zebrafish genetics, live imaging and physiological manipulations.

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