运用系统生物学方法理解分枝杆菌的生存机制。
Systems biology approaches to understanding mycobacterial survival mechanisms.
作者信息
Boshoff Helena I M, Lun Desmond S
机构信息
Tuberculosis Research Section, LCID, NIAID, NIH, Building 33, 9000 Rockville Pike, Bethesda, MD 20892.
出版信息
Drug Discov Today Dis Mech. 2010 Spring;7(1):e75-e82. doi: 10.1016/j.ddmec.2010.09.008.
The advent of high-throughput platforms for the interrogation of biological systems at the cellular and molecular level have allowed living cells to be observed and understood at a hitherto unprecedented level of detail and have enabled the construction of comprehensive, predictive in silico models. Here, we review the application of such high-throughput, systems-biological techniques to mycobacteria-specifically to the pernicious human pathogen Mycobacterium tuberculosis (MTb) and its ability to survive in human hosts. We discuss the development and application of transcriptomic, proteomic, regulomic, and metabolomic techniques for MTb as well as the development and application of genome-scale in silico models. Thus far, systems-biological approaches have largely focused on in vitro models of MTb growth; reliably extending these approaches to in vivo conditions relevant to infection is a significant challenge for the future that holds the ultimate promise of novel chemotherapeutic interventions.
用于在细胞和分子水平上探究生物系统的高通量平台的出现，使得活细胞能够在前所未有的详细程度上被观察和理解，并促成了全面的、可预测的计算机模拟模型的构建。在此，我们综述此类高通量系统生物学技术在分枝杆菌中的应用——具体而言是在有害的人类病原体结核分枝杆菌（MTb）及其在人类宿主中生存能力方面的应用。我们讨论了用于MTb的转录组学、蛋白质组学、调控组学和代谢组学技术的发展与应用，以及基因组规模计算机模拟模型的发展与应用。到目前为止，系统生物学方法主要集中在MTb生长的体外模型上；将这些方法可靠地扩展到与感染相关的体内条件是未来一项重大挑战，但有望带来新型化疗干预措施。
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