Computational design of molecular motors as nanocircuits in Leishmaniasis

Abstract

Cutaneous leishmaniasis is the most common form of lesihmaniasis, caused by and is spread by the bite of a sandfly This species infects the Leishmania major . macrophages and dendritic cells Due to multi-drug resistance, there is a need for a new therapeutic technique. Recently, a novel molecular motor of , Myosin XXI, was classified and characterized. In addition, the drug Leishmania 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, using Tinker Cell. When inducer is added, the circuit has been in silico, 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.

Synthetic biology for combating leishmaniasis

“…They basically looked at the potential of synthetic biology to address and rewire the immune response from Th2 to Th1 type during the early stage of leishmanial infection, which is controlled by the SOCS1 and Suppressor Of Cytokine Signaling 3 (SOCS3), immune axis. Kosey and Singh (2017) investigated a novel molecular motor myosin XXI which may result in newer leishmaniasis treatment modalities. It is a revolutionary concept that opens up a whole new world of therapeutic possibilities to employ a nanocircuit made up of a connected bistable switch and repressilator to cure the disease.…”

“… Kosey and Singh (2017) investigated a novel molecular motor myosin XXI which may result in newer leishmaniasis treatment modalities. It is a revolutionary concept that opens up a whole new world of therapeutic possibilities to employ a nanocircuit made up of a connected bistable switch and repressilator to cure the disease.…”

Computational design of molecular motors as nanocircuits in Leishmaniasis

“…The file contains all the source codes and other files for the nanocircuit designing, simulation and validation. doi, 10.5256/f1000research.10701.d150383 ( Kosey & Singh, 2017 ).…”