Wilson RA

References (4)

Title : A systematically improved high quality genome and transcriptome of the human blood fluke Schistosoma mansoni - Protasio_2012_PLoS.Negl.Trop.Dis_6_e1455
Author(s) : Protasio AV , Tsai IJ , Babbage A , Nichol S , Hunt M , Aslett MA , De Silva N , Velarde GS , Anderson TJ , Clark RC , Davidson C , Dillon GP , Holroyd NE , LoVerde PT , Lloyd C , McQuillan J , Oliveira G , Otto TD , Parker-Manuel SJ , Quail MA , Wilson RA , Zerlotini A , Dunne DW , Berriman M
Ref : PLoS Negl Trop Dis , 6 :e1455 , 2012
Abstract : Schistosomiasis is one of the most prevalent parasitic diseases, affecting millions of people in developing countries. Amongst the human-infective species, Schistosoma mansoni is also the most commonly used in the laboratory and here we present the systematic improvement of its draft genome. We used Sanger capillary and deep-coverage Illumina sequencing from clonal worms to upgrade the highly fragmented draft 380 Mb genome to one with only 885 scaffolds and more than 81% of the bases organised into chromosomes. We have also used transcriptome sequencing (RNA-seq) from four time points in the parasite's life cycle to refine gene predictions and profile their expression. More than 45% of predicted genes have been extensively modified and the total number has been reduced from 11,807 to 10,852. Using the new version of the genome, we identified trans-splicing events occurring in at least 11% of genes and identified clear cases where it is used to resolve polycistronic transcripts. We have produced a high-resolution map of temporal changes in expression for 9,535 genes, covering an unprecedented dynamic range for this organism. All of these data have been consolidated into a searchable format within the GeneDB (www.genedb.org) and SchistoDB (www.schistodb.net) databases. With further transcriptional profiling and genome sequencing increasingly accessible, the upgraded genome will form a fundamental dataset to underpin further advances in schistosome research.
ESTHER : Protasio_2012_PLoS.Negl.Trop.Dis_6_e1455
PubMedSearch : Protasio_2012_PLoS.Negl.Trop.Dis_6_e1455
PubMedID: 22253936
Gene_locus related to this paper: schma-c4qmk4 , schma-g4vhz1 , schma-g4vgd5

Title : The genome of the blood fluke Schistosoma mansoni - Berriman_2009_Nature_460_352
Author(s) : Berriman M , Haas BJ , LoVerde PT , Wilson RA , Dillon GP , Cerqueira GC , Mashiyama ST , Al-Lazikani B , Andrade LF , Ashton PD , Aslett MA , Bartholomeu DC , Blandin G , Caffrey CR , Coghlan A , Coulson R , Day TA , Delcher A , DeMarco R , Djikeng A , Eyre T , Gamble JA , Ghedin E , Gu Y , Hertz-Fowler C , Hirai H , Hirai Y , Houston R , Ivens A , Johnston DA , Lacerda D , Macedo CD , McVeigh P , Ning Z , Oliveira G , Overington JP , Parkhill J , Pertea M , Pierce RJ , Protasio AV , Quail MA , Rajandream MA , Rogers J , Sajid M , Salzberg SL , Stanke M , Tivey AR , White O , Williams DL , Wortman J , Wu W , Zamanian M , Zerlotini A , Fraser-Liggett CM , Barrell BG , El-Sayed NM
Ref : Nature , 460 :352 , 2009
Abstract : Schistosoma mansoni is responsible for the neglected tropical disease schistosomiasis that affects 210 million people in 76 countries. Here we present analysis of the 363 megabase nuclear genome of the blood fluke. It encodes at least 11,809 genes, with an unusual intron size distribution, and new families of micro-exon genes that undergo frequent alternative splicing. As the first sequenced flatworm, and a representative of the Lophotrochozoa, it offers insights into early events in the evolution of the animals, including the development of a body pattern with bilateral symmetry, and the development of tissues into organs. Our analysis has been informed by the need to find new drug targets. The deficits in lipid metabolism that make schistosomes dependent on the host are revealed, and the identification of membrane receptors, ion channels and more than 300 proteases provide new insights into the biology of the life cycle and new targets. Bioinformatics approaches have identified metabolic chokepoints, and a chemogenomic screen has pinpointed schistosome proteins for which existing drugs may be active. The information generated provides an invaluable resource for the research community to develop much needed new control tools for the treatment and eradication of this important and neglected disease.
ESTHER : Berriman_2009_Nature_460_352
PubMedSearch : Berriman_2009_Nature_460_352
PubMedID: 19606141
Gene_locus related to this paper: schma-ACHE1 , schma-ACHE2 , schma-c4qb79 , schma-c4qmk4 , schma-g4v9h7 , schma-BCHE , schma-g4vmf3

Title : Phosphonate inhibitors of antigen 85C, a crucial enzyme involved in the biosynthesis of the Mycobacterium tuberculosis cell wall - Gobec_2004_Bioorg.Med.Chem.Lett_14_3559
Author(s) : Gobec S , Plantan I , Mravljak J , Wilson RA , Besra GS , Kikelj D
Ref : Bioorganic & Medicinal Chemistry Lett , 14 :3559 , 2004
Abstract : The first phosphonate inhibitors of antigen 85C--a major protein component of the Mycobacterium tuberculosis cell wall possessing mycolyltransferase activity were prepared using structure-based design. These potential novel antituberculosis agents, consisting of a phosphonate moiety, hydrophobic alkyl chain and a simple trehalose-mimicking aromatic structure, were designed as tetrahedral transition-state analogue inhibitors of antigen 85C, which catalyzes the key mycolyltransferase reaction involved in cell wall biosynthesis.
ESTHER : Gobec_2004_Bioorg.Med.Chem.Lett_14_3559
PubMedSearch : Gobec_2004_Bioorg.Med.Chem.Lett_14_3559
PubMedID: 15177473

Title : The structure of Mycobacterium tuberculosis MPT51 (FbpC1) defines a new family of non-catalytic alpha\/beta hydrolases - Wilson_2004_J.Mol.Biol_335_519
Author(s) : Wilson RA , Maughan WN , Kremer L , Besra GS , Futterer K
Ref : Journal of Molecular Biology , 335 :519 , 2004
Abstract : Mycobacterium tuberculosis, the causative agent of tuberculosis, is known to secrete a number of highly immunogenic proteins that are thought to confer pathogenicity, in part, by mediating binding to host tissues. Among these secreted proteins are the trimeric antigen 85 (Ag85) complex and the related MPT51 protein, also known as FbpC1. While the physiological function of Ag85, a mycolyltransferase required for the biosynthesis of the cell wall component alpha,alpha'-trehalose dimycolate (or cord factor), has been identified recently, the function of the closely related MPT51 (approximately 40% identity with the Ag85 components) remains to be established. The crystal structure of M.tuberculosis MPT51, determined to 1.7 A resolution, shows that MPT51, like the Ag85 components Ag85B and Ag85C2, folds as an alpha/beta hydrolase, but it does not contain any of the catalytic elements required for mycolyltransferase activity. Moreover, the absence of a recognizable alpha,alpha'-trehalose monomycolate-binding site and the failure to detect an active site suggest that the function of MPT51 is of a non-enzymatic nature and that MPT51 may in fact represent a new family of non-catalytic alpha/beta hydrolases. Previous experimental evidence and the structural similarity to some integrins and carbohydrate-binding proteins led to the hypothesis that MPT51 might have a role in host tissue attachment, whereby ligands may include the serum protein fibronectin and small sugars.
ESTHER : Wilson_2004_J.Mol.Biol_335_519
PubMedSearch : Wilson_2004_J.Mol.Biol_335_519
PubMedID: 14672660
Gene_locus related to this paper: myctu-mpt51