{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T05:05:47Z","timestamp":1772168747601,"version":"3.50.1"},"update-to":[{"DOI":"10.12688\/f1000research.10701.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2017,8,3]],"date-time":"2017-08-03T00:00:00Z","timestamp":1501718400000}}],"reference-count":13,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2017,8,3]],"date-time":"2017-08-03T00:00:00Z","timestamp":1501718400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Biotechnology, Government of India","award":["BT\/PR10286\/BRB\/10\/1258\/2013"],"award-info":[{"award-number":["BT\/PR10286\/BRB\/10\/1258\/2013"]}]}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns4:p>\n                    Cutaneous leishmaniasis is the most common form of leishmaniasis, caused by\n                    <ns4:italic>Leishmania major<\/ns4:italic>\n                    and is spread by the bite of a sandfly\n                    <ns4:italic>.<\/ns4:italic>\n                    This species infects the macrophages and dendritic cells Due to multi-drug resistance, there is a need for a new therapeutic technique. Recently, a novel molecular motor of\n                    <ns4:italic>Leishmania<\/ns4:italic>\n                    , Myosin XXI, was classified and characterized. In addition, the drug resistance in this organism has been linked with the overexpression of ABC transporters. Systems biology aims to study the simulation and modeling of natural biological systems whereas synthetic biology deals with building novel and artificial biological parts and devices \u00a0Together they have contributed enormously to drug discovery, vaccine design and development, infectious disease detection and diagnostics. Synthetic genetic regulatory networks with desired properties, like toggling and oscillation have been proposed to be useful for gene therapy. In this work, a nanocircuit with coupled bistable switch \u2013 repressilator \u00a0has been designed, simulated in the presence and absence of inducer,\n                    <ns4:italic>in silico,<\/ns4:italic>\n                    using Tinker Cell. When inducer is added, the circuit has been shown to produce reporter at high levels, which will impair the activity of Myosin XXI and ABC transporters. Validation of the circuit was also performed using GRENITS and BoolNet. The influence of inducer on the working of the circuit, i.e., the type of gene expression, response time delay, the steady states formed by the circuit and the quasipotential landscape of the circuit were performed. It was found that the addition of inducer reduced the response time delay in the graded type of gene expression and removed the multiple intermediate attractors of the circuit. Thus, the inducer increased the probability of the circuit to be present in the dominant stable state with high reporter concentration and hence the designed nanocircuit may be used for the treatment of leishmaniasis\n                    <ns4:italic>.<\/ns4:italic>\n                  <\/ns4:p>","DOI":"10.12688\/f1000research.10701.2","type":"journal-article","created":{"date-parts":[[2017,8,3]],"date-time":"2017-08-03T11:10:17Z","timestamp":1501758617000},"page":"94","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Computational design of molecular motors as nanocircuits in Leishmaniasis"],"prefix":"10.12688","volume":"6","author":[{"given":"Dipali","family":"Kosey","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3817-8819","authenticated-orcid":false,"given":"Shailza","family":"Singh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2560","published-online":{"date-parts":[[2017,8,3]]},"reference":[{"key":"ref-1","doi-asserted-by":"publisher","first-page":"E227-E236","DOI":"10.1073\/pnas.1319285110","article-title":"Calmodulin regulates dimerization, motility, and lipid binding of Leishmania myosin XXI.","volume":"111","author":"C Batters","year":"2014","journal-title":"Proc Natl Acad Sci U S A."},{"key":"ref-2","doi-asserted-by":"publisher","DOI":"10.1042\/csb0001003","article-title":"\u2018Ion Channels\u2019.","author":"M Berridge","year":"2012","journal-title":"Cell Signaling 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Xu","year":"2006","journal-title":"Carcinogenesis."}],"container-title":["F1000Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/f1000research.com\/articles\/6-94\/v2\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/6-94\/v2\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/6-94\/v2\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,12,6]],"date-time":"2018-12-06T08:54:06Z","timestamp":1544086446000},"score":1,"resource":{"primary":{"URL":"https:\/\/f1000research.com\/articles\/6-94\/v2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,8,3]]},"references-count":13,"URL":"https:\/\/doi.org\/10.12688\/f1000research.10701.2","relation":{"has-review":[{"id-type":"doi","id":"10.5256\/f1000research.13332.r24789","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.13332.r24789","asserted-by":"object"}]},"ISSN":["2046-1402"],"issn-type":[{"value":"2046-1402","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,8,3]]},"assertion":[{"value":"Indexed","URL":"https:\/\/f1000research.com\/articles\/6-94\/v2#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.5256\/f1000research.13332.r24789, Jaime J. Seguel, Department of Computer Science and Engineering, College of Engineering, University of Puerto Rico at Mayag\u00fcez, Mayag\u00fcez, Puerto Rico, 21 Aug 2017, version 2, indexed","URL":"https:\/\/f1000research.com\/articles\/6-94\/v2#referee-response-24789","order":0,"name":"referee-response-24789","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.11538.r23063, Prinessa Chellan, Department of Chemistry and Polymer Science, Stellenbosch University, Stellenbosch, South Africa, 31 Jul 2017, version 1, 1 approved, 1 approved with reservations","URL":"https:\/\/f1000research.com\/articles\/6-94\/v1#referee-response-23063","order":1,"name":"referee-response-23063","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"The authors would like to thank Department of Biotechnology, Ministry of Science and technology, Government of India (BT\/PR10286\/BRB\/10\/1258\/2013) for funding the work. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":2,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Data associated with the article are available under the terms of the Creative Commons Zero \"No rights reserved\" data waiver (CC0 1.0 Public domain dedication).","order":0,"name":"copyright-info","label":"Copyright"}]}}