dictyNews Electronic Edition Volume 39, number 28 October 4, 2013 Please submit abstracts of your papers as soon as they have been accepted for publication by sending them to dicty@northwestern.edu or by using the form at http://dictybase.org/db/cgi-bin/dictyBase/abstract_submit. Back issues of dictyNews, the Dicty Reference database and other useful information is available at dictyBase - http://dictybase.org. Follow dictyBase on twitter: http://twitter.com/dictybase ========= Abstracts ========= The search for better epilepsy treatments: from slime mould to coconuts Matthew C. Walker*1 and Robin S.B. Williams 1 * Department of Clinical and Experimental Epilepsy, Institute of Neurology, University College London, London WC1N 3BG, U.K.   Centre for Biomedical Sciences, School of Biological Sciences, Royal Holloway University of London, Egham TW20 0EX, U.K. 1 joint corresponding authors Biochemical Society Transactions (Review), In Press Drug-resistant epilepsy has remained a problem since the inception of antiepileptic drug development, despite the large variety of antiepileptic drugs available today. Moreover, the mechanism-of- action of these drugs is often unknown. This is due to the widespread screening of compounds through animal models. We have taken a different approach to antiepileptic drug discovery and have identified a biochemical pathway in Dictyostelium discoideum (a Ôslime mouldÕ) that may relate to the mechanism-of-action of valproate, one of the most commonly used and effective antiepileptic drugs. Through screening in this pathway, we have been able to identify a whole host of fatty acids and fatty-acid-derivatives with potential antiepileptic activity; this was then confirmed in in vitro and in vivo mammalian seizure models. Some of these compounds are more potent than valproate and potentially lack many of the major side effects of valproate (including birth defects and liver toxicity). In addition, one of the compounds that we have identified is a major constituent of the ketogenic diet, strongly arguing that it may be the fatty acids and not the ketogenesis that are mediating the effect of this diet. Submitted by Robin Williams [robin.williams@rhul.ac.uk] --------------------------------------------------------------------------- WASH-driven actin polymerization is required for efficient mycobacterial phagosome maturation arrest Margot Kolonko1, Anna Christina Geffken2, Tanja Blumer1,3, Kristine Hagens2, Ulrich Emil Schaible2 and Monica Hagedorn1 1Bernhard Nocht Institute for Tropical Medicine, Bernhard-Nocht-Str. 74, 20359 Hamburg, Germany 2Research Center Borstel, Priority Program Infections, Parkallee 1-40, 23458 Borstel, Germany 3current address: Dept. of Biomedicine, University of Basel, Hebelstr. 20, 4031 Basel, Switzerland Cellular Microbiology, in press Pathogenic mycobacteria survive in phagocytic host cells primarily as a result of their ability to prevent fusion of their vacuole with lysosomes, thereby avoiding a bactericidal environment. The molecular mechanisms to establish and maintain this replication compartment are not well understood. By combining molecular and microscopical approaches we show here that after phagocytosis the actin nucleation-promoting factor WASH associates and generates F-actin on the mycobacterial vacuole. Disruption of WASH or depolymerization of F-actin leads to the accumulation of the proton-pumping V-ATPase around the mycobacterial vacuole, its acidification and reduces the viability of intracellular mycobacteria. This effect is observed for M. marinum in the model phagocyte Dictyostelium but also for M. marinum and M. tuberculosis in mammalian phagocytes. This demonstrates an evolutionarily conserved mechanism by which pathogenic mycobacteria subvert the actin- polymerization activity of WASH to prevent phagosome acidification and maturation, as a prerequisite to generate and maintain a replicative niche. Submitted by Monica Hagedorn [hagedorn@bnitm.de] ============================================================== [End dictyNews, volume 39, number 28]