Publications by authors named "Milsee Mol"

Systems and synthetic biology in the coming era has the ability to manipulate, stimulate and engineer cells to counteract the pathogenic immune response. The inherent biological complexities associated with the creation of a device allow capitalizing the biotechnological resources either by simply administering a recombinant cytokine or just reprogramming the immune cells. The strategy outlined, adopted and discussed may mark the beginning with promising therapeutics based on the principles of synthetic immunology.

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With the advent of synthetic biology in medicine many synthetic or engineered proteins have made their way to therapeutics and diagnostics. In this paper, the downstream gene network of CD14-TNF-EGFR pathway in leishmaniasis, a tropical disease, is reconstructed. Network analysis showed that NFkB links the signaling and gene network, used as a point of intervention through a synthetic circuit embedded within the negative autoregulatory feedback loop.

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Whole genome sequencing projects running in various laboratories around the world has generated immense data. A systematic phylogenetic analysis of this data shows that genome complexity goes on decreasing as it evolves, due to its modular nature. This modularity can be harnessed to minimize the genome further to reduce it with the bare minimum essential genes.

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Synthetic biology is an investigative and constructive means of understanding the complexities of biology. Substantial progress in the fields has resulted in the creation of synthetic gene circuits, which when uploaded into the appropriate nanoliposomal vehicle, can be used for a tunable response in a cell. These tunable elements can be applied to treat diseased condition for a transition to a healthy state.

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Functional genomics is considered a powerful tool that helps understand the relation between an organism's genotype and possible phenotypes. Volumes of data generated on several 'omics' platforms have revealed the network complexities underlying biological processes. Systems and synthetic biology have garnered much attention because of the ability to infer and comprehend the uncertainties associated with such complexities.

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Understanding network topology through embracing the global dynamical regulation of genes in an active state space rather than traditional one-gene-one trait approach facilitates the rational drug development process. Schistosomiasis, a neglected tropical disease, has glycerophospholipids as abundant molecules present on its surface. Lack of effective clinical solutions to treat pathogens encourages us to carry out systems-level studies that could contribute to the development of an effective therapy.

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Leishmania major causes cutaneous form of Leishmaniasis affecting 21 million people in developing countries. Overuse of the chemotherapeutics against leishmaniasis has resulted in the development of drug resistance in the parasite. To surmount this emerging threat we have attempted to target the surface molecules.

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Network of signaling proteins and functional interaction between the infected cell and the leishmanial parasite, though are not well understood, may be deciphered computationally by reconstructing the immune signaling network. As we all know signaling pathways are well-known abstractions that explain the mechanisms whereby cells respond to signals, collections of pathways form networks, and interactions between pathways in a network, known as cross-talk, enables further complex signaling behaviours. In silico perturbations can help identify sensitive crosstalk points in the network which can be pharmacologically tested.

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Building circuits and studying their behavior in cells is a major goal of systems and synthetic biology. Synthetic biology enables the precise control of cellular states for systems studies, the discovery of novel parts, control strategies, and interactions for the design of robust synthetic systems. To the best of our knowledge, there are no literature reports for the synthetic circuit construction for protozoan parasites.

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Background: Modulated immune signal (CD14-TLR and TNF) in leishmaniasis can be linked to EGFR pathway involved in wound healing, through crosstalk points. This signaling network can be further linked to a synthetic gene circuit acting as a positive feedback loop to elicit a synchronized intercellular communication among the immune cells which may contribute to a better understanding of signaling dynamics in leishmaniasis.

Methods: Network reconstruction with positive feedback loop, simulation (ODE 15s solver) and sensitivity analysis of CD14-TLR, TNF and EGFR was done in SimBiology (MATLAB 7.

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