By Michael P. Stumpf, Brian D. Robertson (auth.), Helena I. Boshoff, Clifton E. Barry III (eds.)
Systems biology is an rising self-discipline that experiences the underlying community constitution and the dynamics of metabolism, cells or complete organisms. It goals to enquire all interacting parts concurrently and calls for info from excessive throughput innovations. those information from the "omic" sciences are computed and used to construct in silico types of organic platforms that eventually will turn out to be a useful device in drug development.
This e-book brings jointly many of the fields of useful genomics and platforms biology that supply details on metabolic functionality with a different emphasis at the id of drug ambitions. It contains useful examples from a few of the "omic" sciences in addition to theoretical examples of ways built-in wisdom of those sciences could be utilized to drug discovery. it really is of curiosity to researchers within the pharmaceutical drug discovery surroundings, in addition to these within the educational box with an curiosity within the practical program of the "omic" sciences.
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Extra info for Systems Biological Approaches in Infectious Diseases
Example text
For instance, the antibiotic trovafloxacin inhibiting the bacterial DNA gyrase and topoisomerase IV belongs to a generally well tolerated class of quinolones. Before the regulatory approval of trovafloxacin in 1997 there were no cases of hepatic failure in more than 7,000 patients. Since then, more than 2 million people have received this drug, resulting in 150 cases of reported liver toxicity [66]; however, the exact mechanism underlying this rare adverse effect has not yet been determined. Recently, it has been reported that comparative transcriptional profiling of trovafloxacin and other quinolones using isolated human hepatocytes revealed unique changes in mRNA levels triggered in the cells treated with trovafloxacin.
The recent drop in cost of commercial microarrays will certainly make transcriptional profiling more accessible for the various antimicrobial research applications in industrial as well as academic environments. 26 Applications of transcriptional profiling in antibiotics discovery and development 3 Comparison of the capabilities of transcriptomics and proteomics RNA polymerase produces mRNA molecules, which represent the templates for protein synthesis. The transcriptome of a bacterial cell is therefore only an indirect indicator of a bacterium’s physiological state, as it does not provide information about the proteins and metabolites, which determine the biochemical processes in the cell.
In this study, microarrays were also used to determine the target specificity of those compounds. Such studies are pioneering the identification of novel targets of chemical entities that interfere with virulence or resistance mechanisms of bacteria. In contrast to the previous examples, it should be noted that the targets currently preferred in the pharmaceutical industry are in vitro and in vivo essential targets, which are expressed under all growth conditions in a bacterium. In fact, the targets inhibited by the anti-infectives established in medicinal practice are largely represented by such ‘essential’ gene products.