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Author (up) Baylis, H.A.; Vazquez-Manrique, R.P. file  url
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  Title Genetic analysis of IP3 and calcium signalling pathways in C. elegans Type Journal Article
  Year 2012 Publication Biochimica et Biophysica Acta Abbreviated Journal Biochim Biophys Acta  
  Volume 1820 Issue 8 Pages 1253-1268  
  Keywords Animals; Caenorhabditis elegans--genetics, metabolism, physiology; Caenorhabditis elegans Proteins--genetics, metabolism; Calcium Signaling; Inositol 1,4,5-Trisphosphate Receptors--genetics, metabolism; Inositol Phosphates--physiology; Mutagenesis; Phenotype; Protein Interaction Maps; RNA Interference; Reverse Genetics  
  Abstract BACKGROUND: The nematode, Caenorhabditis elegans is an established model system that is particularly well suited to genetic analysis. C. elegans is easily manipulated and we have an in depth knowledge of many aspects of its biology. Thus, it is an attractive system in which to pursue integrated studies of signalling pathways. C. elegans has a complement of calcium signalling molecules similar to that of other animals. SCOPE OF REVIEW: We focus on IP3 signalling. We describe how forward and reverse genetic approaches, including RNAi, have resulted in a tool kit which enables the analysis of IP3/Ca2+ signalling pathways. The importance of cell and tissue specific manipulation of signalling pathways and the use of epistasis analysis are highlighted. We discuss how these tools have increased our understanding of IP3 signalling in specific developmental, physiological and behavioural roles. Approaches to imaging calcium signals in C. elegans are considered. MAJOR CONCLUSIONS: A wide selection of tools is available for the analysis of IP3/Ca2+ signalling in C. elegans. This has resulted in detailed descriptions of the function of IP3/Ca2+ signalling in the animal's biology. Nevertheless many questions about how IP3 signalling regulates specific processes remain. GENERAL SIGNIFICANCE: Many of the approaches described may be applied to other calcium signalling systems. C. elegans offers the opportunity to dissect pathways, perform integrated studies and to test the importance of the properties of calcium signalling molecules to whole animal function, thus illuminating the function of calcium signalling in animals. This article is part of a Special Issue entitled Biochemical, biophysical and genetic approaches to intracellular calcium signalling.  
  Call Number Serial 258  
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Author (up) Schenone, M.; Dancik, V.; Wagner, B.K.; Clemons, P.A. file  url
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  Title Target identification and mechanism of action in chemical biology and drug discovery Type Journal Article
  Year 2013 Publication Nature Chemical Biology Abbreviated Journal Nat Chem Biol  
  Volume 9 Issue 4 Pages 232-240  
  Keywords Animals; Biomarkers, Pharmacological/chemistry/*metabolism; *Drug Discovery; *Drug Evaluation, Preclinical; *High-Throughput Screening Assays; Humans; Isotope Labeling; Mass Spectrometry; Molecular Targeted Therapy; Phenotype; RNA Interference; Reverse Genetics; Saccharomyces cerevisiae/drug effects/genetics/metabolism; Small Molecule Libraries/chemistry/*metabolism/pharmacology; Validation Studies as Topic  
  Abstract Target-identification and mechanism-of-action studies have important roles in small-molecule probe and drug discovery. Biological and technological advances have resulted in the increasing use of cell-based assays to discover new biologically active small molecules. Such studies allow small-molecule action to be tested in a more disease-relevant setting at the outset, but they require follow-up studies to determine the precise protein target or targets responsible for the observed phenotype. Target identification can be approached by direct biochemical methods, genetic interactions or computational inference. In many cases, however, combinations of approaches may be required to fully characterize on-target and off-target effects and to understand mechanisms of small-molecule action.  
  Call Number Serial 1592  
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