dictyNews Electronic Edition Volume 35, number 16 Dec 3, 2010 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 ========= Molecular pharmacology in a simple model system: implicating MAP kinase and phosphoinositide signalling in bipolar disorder Marthe H.R. Ludtmann, Katrina Boeckeler and Robin S.B. Williams Centre for Biomedical Sciences, School of Biological Sciences, Royal Holloway University of London, Egham TW20 0EX, UK Seminars in Cell and Developmental Biology, in press Understanding the mechanisms of drug action has been the primary focus for pharmacological researchers, traditionally using rodent models. However, non-sentient model systems are now increasingly being used as an alternative approach to better understand drug action or targets. One of these model systems, the social amoeba Dictyostelium, enables the rapid ablation or over-expression of genes, and the subsequent use of isogenic cell culture for the analysis of cell signalling pathways in pharmacological research. The model also supports an increasingly important ethical view of research, involving the reduction, replacement and refinement of animals in biomedical research. This review outlines the use of Dictyostelium in understanding the pharmacological action of two commonly used bipolar disorder treatments (valproic acid and lithium). Both of these compounds regulate mitogen activated protein (MAP) kinase and inositol phospholipid-based signalling by unknown means. Analysis of the molecular pathways targeted by these drugs in Dictyostelium and translation of discoveries to animal systems has helped to further understand the molecular mechanisms of these bipolar disorder treatments. Submitted by Robin Williams [robin.williams@rhul.ac.uk] -------------------------------------------------------------------------------- Evolutionary crossroads in developmental biology: Dictyostelium discoideum Pauline Schaap College of Life Sciences, University of Dundee, Dundee, UK. Development, in press Dictyostelium discoideum belongs to a group of multicellular life forms that can also exist for long periods as single cells. This ability to shift between uni- and multicellularity makes the group ideal for studying the genetic changes that occurred at the crossroad between uni- and multicellular life. In this Primer, I discuss the mechanisms that control multicellular development in Dictyostelium discoideum, and reconstruct how some of these mechanisms evolved from a stress response in the unicellular ancestor. Submitted byPauline Schaap [p.schaap@dundee.ac.uk] -------------------------------------------------------------------------------- Evolution of Pseudomonas aeruginosa virulence revealed in a Dictyostelium discoideum host model Emmanuelle Lelong, Anna Marchetti, Marianne Simon, Jane L. Burns, Christian van Delden, Thilo Kšhler, Pierre Cosson* * Corresponding author: Pierre.Cosson@unige.ch Clinical Microbiology and Infection, in press Pseudomonas aeruginosa can cause acute lung infections in intubated patients or chronic infections in patients with cystic fibrosis (CF). In both situations, P. aeruginosa accumulates specific mutations, in particular in the lasR quorum-sensing regulator gene. Using a Dictyostelium discoideum amoeba model, we assessed whether these mutations affect bacterial virulence. In a collection of clinical isolates from 16 CF patients, initial isolates were fully virulent in 15 patients, but in late isolates collected several years later, virulence was decreased in 8 patients. No significant correlation between genetic inactivation of lasR and decreased virulence was observed. In strains isolated from 10 colonized intubated patients, all initial isolates were fully virulent. Despite the accumulation of lasR-inactivating mutations in strains collected over a three-week period, no decrease in virulence was observed in 8/10 patients. In one intubated patient, the virulent initial strain was replaced a few days later with a different less virulent strain. We observed a gradual decrease in bacterial virulence in only one intubated patient. We conclude that adaptation of P. aeruginosa to chronically infected CF patients can lead to a slow and gradual loss of virulence, as measured in a Dictyostelium model system. However, loss of virulence is not caused predominantly by mutations in lasR. During short-term colonization of intubated patients up to 20 days, a decrease in virulence was exceptional, despite the accumulation of lasR mutations. Submitted by Emanuelle Lelong [emmanuelle.lelong@unige.ch] -------------------------------------------------------------------------------- What does Dictyostelium bring to the study of Pseudomonas infections? Wanessa C Lima, Emmanuelle Lelong, Pierre Cosson Corresponding Author: Dr Pierre Cosson Seminars in Cell and Developmental Biology Bacterial infections are complex events. They are studied in a variety of simple model systems, using mammalian or non-mammalian hosts, all of which fail to reproduce fully the situation in infected patients. Each model presents a combination of conceptual, practical, and ethical advantages and disadvantages. In this review, we detail the use of Dictyostelium discoideum amoebae as a model to study Pseudomonas aeruginosa. More specifically, our aim is to explore what this additional model system can bring to our understanding of Pseudomonas infections. The study of interactions between Dictyostelium amoebae and Pseudomonas provides a view of the selection pressures exerted by environmental predators on Pseudomonas. It also represents a unique system to assess the virulence of very large numbers of Pseudomonas strains. Submitted by Emanuelle Lelong [emmanuelle.lelong@unige.ch] ============================================================== [End dictyNews, volume 35, number 16]