Dictyostelium discoideum—a model for many reasons Sarah J. Annesley ® Paul R. Fisher Received: 7 January 2009 / Accepted: 2 April 2009 / Published online: 22 April 2009 Ó Springer Science+Business Media, LLC. 2009 Abstract The social amoeba or cellular slime mould Dictyostelium discoideum is a ‘‘professional’’ phagocyte that has long been recognized for its value as a biomedical model organism, particularly in studying the actomyosin cytoskeleton and chemotactic motility in non-muscle cells. The complete genome sequence of D. discoideum is known, it is genetically tractable, readily grown clonally as a eukaryotic microorganism and is highly accessible for biochemical, cell biological and physiological studies. These are the properties it shares with other microbial model organisms. However, Dictyostelium combines these with a unique life style, with motile unicellular and mul- ticellular stages, and multiple cell types that offer for study an unparalleled variety of phenotypes and associated sig- nalling pathways. These advantages have led to its recent emergence as a valuable model organism for studying the molecular pathogenesis and treatment of human disease, including a variety of infectious diseases caused by bac- terial and fungal pathogens. Perhaps surprisingly, this organism, without neurons or brain, has begun to yield novel insights into the cytopathology of mitochondrial diseases as well as other genetic and idiopathic disorders affecting the central nervous system. Dictyostelium has also contributed significantly to our understanding of NDP kinase, as it was the Dictyostelium enzyme whose structure was first determined and related to enzymatic activity. The phenotypic richness and tractability of Dictyostelium should provide a fertile arena for future exploration of NDPK’s cellular roles. Keywords Dictyostelium Á Chemotaxis Á Actin cytoskeleton Á Legionella Á Intracellular pathogen Á Mitochondrial disease Á Neurological disease Á NDPK The Dictyostelium model for eukaryotic cell biology and disease Recent phylogenetic studies have demonstrated the exis- tence of three major kingdom-level lineages of eukaryotes that diverged from one another after separating from the plants and other eukaryotes [1]. These sister clades (phylo- genetic groups containing a common ancestor and all of its descendents) are the Metazoa, the Fungi and the Amoebozoa and they include a dozen organisms recognized by the National Institutes of Health as being of particular value as biomedical research models (http://www.nih.gov/science/ models). One of the chosen dozen is the social amoeba or cellular slime mould Dictyostelium discoideum. In this article, we briefly review aspects of Dictyostelium biology that illustrate its value as a model for understanding molecular processes in cell biology and disease. A motile life style with unicellular and multicellular stages Dictyostelium discoideum is a small (10–20 lm diameter), motile soil amoeba with a haploid genome containing six chromosomes that have been completely sequenced [2]. The genome sequence is publicly available along with a rich variety of bioinformatics tools and information at dictyBase [3]. Its study has revealed many proteins and molecular processes in Dictyostelium that were previously thought to be present only in metazoa. For example, the S. J. Annesley Á P. R. Fisher (&) Department of Microbiology, La Trobe University, Bundoora, VIC 3086, Australia e-mail: P.Fisher@latrobe.edu.au URL: http://www.latrobe.edu.au/mcbg/my.html 123 Mol Cell Biochem (2009) 329:73–91 DOI 10.1007/s11010-009-0111-8