{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T00:23:44Z","timestamp":1791073424415,"version":"4.1.0"},"reference-count":23,"publisher":"National Academy of Sciences","issue":"8","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2005,2,22]]},"abstract":"<jats:p>\n                    Genetic manipulation has revolutionized research in the Apicomplexan parasite\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    , the most important causative agent of malaria. However, to date no techniques have been established that allow modifications that are deleterious to blood-stage growth, such as the disruption of essential genes or the expression of dominant-negative transgenes. The recent establishment of a screen for functional transactivators in the related parasite\n                    <jats:italic>Toxoplasma gondii<\/jats:italic>\n                    prompted us to identify transactivators in\n                    <jats:italic>T. gondii<\/jats:italic>\n                    and to examine their functionality in\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    . Tetracycline-responsive minimal promoters were generated based on the characterized\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    calmodulin promoter and used to assess transactivators in\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    . We demonstrate that artificial tetracycline-regulated transactivators isolated in\n                    <jats:italic>T. gondii<\/jats:italic>\n                    are also functional in\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    . By using the tetracycline analogue anhydrotetracycline, efficient, stage-specific gene regulation was achieved in\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    . This regulatable expression technology has clear potential for the study of essential gene function in\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    blood stages. On the other hand, the identified transactivators are not functional in mammalian cells, consistent with the fundamental differences in the mechanism of gene regulation between Apicomplexan parasites and their human hosts.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0500112102","type":"journal-article","created":{"date-parts":[[2005,2,14]],"date-time":"2005-02-14T20:24:30Z","timestamp":1108412670000},"page":"2980-2985","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":100,"title":["Tetracycline analogue-regulated transgene expression in\n                    <i>Plasmodium falciparum<\/i>\n                    blood stages using\n                    <i>Toxoplasma gondii<\/i>\n                    transactivators"],"prefix":"10.1073","volume":"102","author":[{"given":"Markus","family":"Meissner","sequence":"first","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville VIC 3050, Australia; Department of Biological Sciences, Imperial College of Science, Technology, and Medicine, Imperial College Road, London SW7 2AZ, United Kingdom; and Abteilung Parasitologie, Hygiene-Institut, Universit\u00e4tsklinikum Heidelberg, Im Neuenheimer Feld 324, D-69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Efrosinia","family":"Krejany","sequence":"additional","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville VIC 3050, Australia; Department of Biological Sciences, Imperial College of Science, Technology, and Medicine, Imperial College Road, London SW7 2AZ, United Kingdom; and Abteilung Parasitologie, Hygiene-Institut, Universit\u00e4tsklinikum Heidelberg, Im Neuenheimer Feld 324, D-69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul R.","family":"Gilson","sequence":"additional","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville VIC 3050, Australia; Department of Biological Sciences, Imperial College of Science, Technology, and Medicine, Imperial College Road, London SW7 2AZ, United Kingdom; and Abteilung Parasitologie, Hygiene-Institut, Universit\u00e4tsklinikum Heidelberg, Im Neuenheimer Feld 324, D-69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tania F.","family":"de Koning-Ward","sequence":"additional","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville VIC 3050, Australia; Department of Biological Sciences, Imperial College of Science, Technology, and Medicine, Imperial College Road, London SW7 2AZ, United Kingdom; and Abteilung Parasitologie, Hygiene-Institut, Universit\u00e4tsklinikum Heidelberg, Im Neuenheimer Feld 324, D-69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Soldati","sequence":"additional","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville VIC 3050, Australia; Department of Biological Sciences, Imperial College of Science, Technology, and Medicine, Imperial College Road, London SW7 2AZ, United Kingdom; and Abteilung Parasitologie, Hygiene-Institut, Universit\u00e4tsklinikum Heidelberg, Im Neuenheimer Feld 324, D-69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brendan S.","family":"Crabb","sequence":"additional","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville VIC 3050, Australia; Department of Biological Sciences, Imperial College of Science, Technology, and Medicine, Imperial College Road, London SW7 2AZ, United Kingdom; and Abteilung Parasitologie, Hygiene-Institut, Universit\u00e4tsklinikum Heidelberg, Im Neuenheimer Feld 324, D-69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2005,2,14]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1368-7646(02)00085-7"},{"key":"e_1_3_2_2_2","first-page":"263","volume":"270","year":"2004","unstructured":"Crabb, B. S., Rug, M., Gilberger, T. W., Thompson, J. K., Triglia, T., Maier, A. G. & Cowman, A. F. (2004) Methods Mol. Biol. 270, 263-276.15153633","journal-title":"Methods Mol. Biol."},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/21.5.1231"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(03)01023-7"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/29.22.e115"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1074553"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.12.5547"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.14.7289"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-6851(03)00118-X"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7761835"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/35002615"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.24.14010"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.781840"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.2307\/3280287"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.20.10931"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/0042-6822(73)90341-3"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1995.mmi_18030437.x"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.040573197"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.130192197"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-6851(97)00143-6"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.4.973"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/19.8.1794"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/29.3.716"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0500112102","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T10:08:03Z","timestamp":1649758083000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0500112102"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,2,14]]},"references-count":23,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2005,2,22]]}},"alternative-id":["10.1073\/pnas.0500112102"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0500112102","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,2,14]]},"assertion":[{"value":"2004-11-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2005-02-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}