Dataset Information

Fast Track to Discover Novel Promoters in Rice.

ABSTRACT: Promoters are key components for the application of biotechnological techniques in crop plants. Reporter genes such as GUS or GFP have been used to test the activity of promoters for diverse applications. A huge number of T-DNAs carrying promoterless GUS near their right borders have been inserted into the rice genome, and 105,739 flanking sequence tags from rice lines with this T-DNA insertion have been identified, establishing potential promoter trap lines for 20,899 out of 55,986 genes in the rice genome. Anatomical meta-expression data and information on abiotic stress related to these promoter trap lines enable us to quickly identify new promoters associated with various expression patterns. In the present report, we introduce a strategy to identify new promoters in a very short period of time using a combination of meta-expression analysis and promoter trap lines.

SUBMITTER: Yoo YH

PROVIDER: S-EPMC7020180 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Fast Track to Discover Novel Promoters in Rice.

Yoo Yo-Han YH Kim Yu-Jin YJ Moon Sunok S Gho Yun-Shil YS Hong Woo-Jong WJ Kim Eui-Jung EJ Jiang Xu X Jung Ki-Hong KH

Plants (Basel, Switzerland) 20200118 1

Promoters are key components for the application of biotechnological techniques in crop plants. Reporter genes such as GUS or GFP have been used to test the activity of promoters for diverse applications. A huge number of T-DNAs carrying promoterless GUS near their right borders have been inserted into the rice genome, and 105,739 flanking sequence tags from rice lines with this T-DNA insertion have been identified, establishing potential promoter trap lines for 20,899 out o ...[more]

PMID: 31963727

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Project description:BackgroundRepositioning of existing drugs has been suggested as a fast track for developing new anti-malarial agents. The compound libraries of GlaxoSmithKline (GSK), Pfizer and AstraZeneca (AZ) comprising drugs that have undergone clinical studies in other therapeutic areas, but not achieved approval, and a set of US Food and Drug Administration (FDA)-approved drugs and other bio-actives were tested against Plasmodium falciparum blood stages.MethodsMolecules were tested initially against erythrocytic co-cultures of P. falciparum to measure proliferation inhibition using one of the following methods: SYBR®I dye DNA staining assay (3D7, K1 or NF54 strains); [(3)H] hypoxanthine radioisotope incorporation assay (3D7 and 3D7A strain); or 4',6-diamidino-2-phenylindole (DAPI) DNA imaging assay (3D7 and Dd2 strains). After review of the available clinical pharmacokinetic and safety data, selected compounds with low ?M activity and a suitable clinical profile were tested in vivo either in a Plasmodium berghei four-day test or in the P. falciparum Pf3D7(0087/N9) huSCID 'humanized' mouse model.ResultsOf the compounds included in the GSK and Pfizer sets, 3.8% (9/238) had relevant in vitro anti-malarial activity while 6/100 compounds from the AZ candidate drug library were active. In comparison, around 0.6% (24/3,800) of the FDA-approved drugs and other bio-actives were active. After evaluation of available clinical data, four investigational drugs, active in vitro were tested in the P. falciparum humanized mouse model: UK-112,214 (PAF-H1 inhibitor), CEP-701 (protein kinase inhibitor), CEP-1347 (protein kinase inhibitor), and PSC-833 (p-glycoprotein inhibitor). Only UK-112,214 showed significant efficacy against P. falciparum in vivo, although at high doses (ED90 131.3 mg/kg [95% CI 112.3, 156.7]), and parasitaemia was still present 96 hours after treatment commencement. Of the six actives from the AZ library, two compounds (AZ-1 and AZ-3) were marginally efficacious in vivo in a P. berghei model.ConclusionsRepositioning of existing therapeutics in malaria is an attractive proposal. Compounds active in vitro at ?M concentrations were identified. However, therapeutic concentrations may not be effectively achieved in mice or humans because of poor bio-availability and/or safety concerns. Stringent safety requirements for anti-malarial drugs, given their widespread use in children, make this a challenging area in which to reposition therapy.

Dataset Information

Fast Track to Discover Novel Promoters in Rice.

Publications

Fast Track to Discover Novel Promoters in Rice.

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