Versatile control of Plasmodium falciparum gene expression with an inducible protein–RNA interaction
The available tools for conditional gene expression in Plasmodium falciparum are limited. Here, to enable reliable control of target gene expression, we build a system to efficiently modulate translation. We overcame several problems associated with other approaches for regulating gene expression in...
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| Format: | Article |
| Language: | en_US |
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Nature Publishing Group
2015
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| Online Access: | http://hdl.handle.net/1721.1/99502 https://orcid.org/0000-0002-6250-8796 |
| _version_ | 1826205212891676672 |
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| author | Goldfless, Stephen J. Wagner, Jeffrey C. Niles, Jacquin |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Goldfless, Stephen J. Wagner, Jeffrey C. Niles, Jacquin |
| author_sort | Goldfless, Stephen J. |
| collection | MIT |
| description | The available tools for conditional gene expression in Plasmodium falciparum are limited. Here, to enable reliable control of target gene expression, we build a system to efficiently modulate translation. We overcame several problems associated with other approaches for regulating gene expression in P. falciparum. Specifically, our system functions predictably across several native and engineered promoter contexts, and affords control over reporter and native parasite proteins irrespective of their subcellular compartmentalization. Induction and repression of gene expression are rapid, homogeneous and stable over prolonged periods. To demonstrate practical application of our system, we used it to reveal direct links between antimalarial drugs and their native parasite molecular target. This is an important outcome given the rapid spread of resistance, and intensified efforts to efficiently discover and optimize new antimalarial drugs. Overall, the studies presented highlight the utility of our system for broadly controlling gene expression and performing functional genetics in P. falciparum. |
| first_indexed | 2024-09-23T13:09:27Z |
| format | Article |
| id | mit-1721.1/99502 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T13:09:27Z |
| publishDate | 2015 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/995022022-09-28T12:17:05Z Versatile control of Plasmodium falciparum gene expression with an inducible protein–RNA interaction Goldfless, Stephen J. Wagner, Jeffrey C. Niles, Jacquin Massachusetts Institute of Technology. Department of Biological Engineering Goldfless, Stephen J. Wagner, Jeffrey C. Niles, Jacquin The available tools for conditional gene expression in Plasmodium falciparum are limited. Here, to enable reliable control of target gene expression, we build a system to efficiently modulate translation. We overcame several problems associated with other approaches for regulating gene expression in P. falciparum. Specifically, our system functions predictably across several native and engineered promoter contexts, and affords control over reporter and native parasite proteins irrespective of their subcellular compartmentalization. Induction and repression of gene expression are rapid, homogeneous and stable over prolonged periods. To demonstrate practical application of our system, we used it to reveal direct links between antimalarial drugs and their native parasite molecular target. This is an important outcome given the rapid spread of resistance, and intensified efforts to efficiently discover and optimize new antimalarial drugs. Overall, the studies presented highlight the utility of our system for broadly controlling gene expression and performing functional genetics in P. falciparum. National Institutes of Health (U.S.) (Health Director's New Innovator Award 1DP2OD007124) Bill & Melinda Gates Foundation (Grand Challenges Explorations Initiative OPP1069759) National Institute of Environmental Health Sciences (Predoctoral Training Grant 5-T32-ES007020) National Institute of General Medical Sciences (U.S.) (Biotechnology Training Grant 5-T32-GM08334) Thomas and Stacey Siebel Foundation MIT Start-up Funds 2015-10-29T15:19:00Z 2015-10-29T15:19:00Z 2014-11 2014-04 Article http://purl.org/eprint/type/JournalArticle 2041-1723 http://hdl.handle.net/1721.1/99502 Goldfless, Stephen J., Jeffrey C. Wagner, and Jacquin C. Niles. “Versatile Control of Plasmodium Falciparum Gene Expression with an Inducible protein–RNA Interaction.” Nat Comms 5 (November 5, 2014): 5329. https://orcid.org/0000-0002-6250-8796 en_US http://dx.doi.org/10.1038/ncomms6329 Nature Communications Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Nature Publishing Group PMC |
| spellingShingle | Goldfless, Stephen J. Wagner, Jeffrey C. Niles, Jacquin Versatile control of Plasmodium falciparum gene expression with an inducible protein–RNA interaction |
| title | Versatile control of Plasmodium falciparum gene expression with an inducible protein–RNA interaction |
| title_full | Versatile control of Plasmodium falciparum gene expression with an inducible protein–RNA interaction |
| title_fullStr | Versatile control of Plasmodium falciparum gene expression with an inducible protein–RNA interaction |
| title_full_unstemmed | Versatile control of Plasmodium falciparum gene expression with an inducible protein–RNA interaction |
| title_short | Versatile control of Plasmodium falciparum gene expression with an inducible protein–RNA interaction |
| title_sort | versatile control of plasmodium falciparum gene expression with an inducible protein rna interaction |
| url | http://hdl.handle.net/1721.1/99502 https://orcid.org/0000-0002-6250-8796 |
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