Biological network modeling identifies IPCS in Leishmania as a therapeutic target.

Systems biology aims to develop mathematical models of biological systems by integrating experimental and theoretical techniques by leveraging on the genome wide data to unravel the complexity of gene regulation. Despite the availability of effective chemotherapy, leishmaniasis continues to be one of the major parasitic infections that affect the human population worldwide. Currently, little is known of the structural biology of the parasites that are responsible for the disease and few attempts have been made to develop second generation drugs, which may become essential if multi-drug resistance arises. These facts make the discovery of novel drug targets a priority. Multiscale modeling and simulation techniques permit us to study the spatial and temporal properties of large systems to be simulated using atomic-detail structures. The estimation of kinetic parameters for the mathematical modeling provides a basis for iterative manipulation of biochemical pathways. In this paper, emphasis is laid on the discrete regulation of gene or protein expression as modeling can be done based on pure qualitative knowledge about interaction between genes or proteins that is widely available from the existing experimental methodologies. IPC synthase is one of them, believed to play a pivotal role in the pathogenesis of Leishmania sp. and resides in an acidic macrophage phagolysosome, defining a new class of eukaryotic sphingolipid synthases. This work will facilitate the rational development of inhibitors against a protozoan enzyme with no mammalian equivalent, leading to the prospect of anti-protozoal compounds with minimal toxic side effects. Henceforth, it can be said that exploiting the interactome for novel human drug targets could provide new therapeutic avenues towards the treatment of infectious diseases, which could ameliorate the growing clinical challenge of drug-resistant infections.