Kosey , D. and Singh , S. (2017) Computational design of molecular motors as nanocircuits in Leishmaniasis [version 1; referees: 1 approved with reservations]. F1000 Research.

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Abstract

Cutaneous leishmaniasis is the most common form of lesihmaniasis, caused by Leishmania major and is spread by the bite of a sandfly.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 Leishmania, 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 Together 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 – repressilator has been designed, simulated in the presence and absence of inducer, in silico, 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.

Item Type:	Article
Additional Information:	This is Open Access Article
Subjects:	Bioinformatics and Proteomics
Depositing User:	Mr. Rameshwar Nema
Date Deposited:	24 Apr 2017 10:41
Last Modified:	02 Mar 2021 11:57
URI:	http://nccs.sciencecentral.in/id/eprint/418

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