Advances in Parasite Genomics From Sequences to Regulatory Networks 英文参考文献.docVIP

Pearls Advances inParasite Genomics: From Sequences to RegulatoryNetworks ElizabethA.Winzeler* DepartmentofCellBiologyICND202,TheScrippsResearchInstitute,LaJolla,California,UnitedStatesofAmerica Parasiteshavekeptmanysecretsfromtheresearcherswhohave sought to eradicate them over past decades. The mechanisms by which they evade drugs, escape the immune system, regulate switching between genes involved in immune evasion, and orchestrate development have been difficult to elucidate. They havebeensuccessfulatthisinpartbecausetheyaredifficulttokeep inthelaboratory,difficulttobreed,anddifficulttoraiseinsufficient quantitiesforbiochemistry,andbecausetheyparasitizehoststhat arenotidealexperimental subjects. WhilePlasmodium falciparumis lesstractablethanonewouldwish,geneticmanipulationcanstillbe performed.Ontheotherhand,Plasmodiumvivax,whichcannotbe maintained in culture, is even less accessible, and there are few researchtoolsavailable. possibilitythatthekirgeneproductsmayplayamoreactiverolein immune suppression through competition with T cells for CD99 partner molecules rather than just functioning as an antigenic smokescreen,apresumedroleformanyoftheproteinsencodedby highlyvariablePlasmodiummultigenefamilies(vars,stevors,virs). GeneticRegulatoryNetworks In organisms that are relatively difficult to genetically manipulate, genomic methods offer opportunities to define regulatory networks by linking motifs in the promoters of co- expressed genes to the DNA-binding activity of different transcription factors. It was recently shown that sets of co- transcribedgenesinP.falciparumoftenshareshortsequencemotifs upstream of their ATGs at rates not expected by chance [5]. A similar approach has been shown to work in Toxoplasma gondii, where functional annotations served as a substitute for gene expression groupings [10]. Although site-directed mutagenesis in P.falciparumhasvalidatedtheimportanceofsomeofthesemotifs controlling promoter activity, the identity of proteins t