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