Department of Pediatrics, Center for Liver, Digestive and Metabolic Diseases, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
Parasitology. 2010 Aug;137(9):1333-41. doi: 10.1017/S0031182010000466. Epub 2010 May 6.
African trypanosomes have emerged as promising unicellular model organisms for the next generation of systems biology. They offer unique advantages, due to their relative simplicity, the availability of all standard genomics techniques and a long history of quantitative research. Reproducible cultivation methods exist for morphologically and physiologically distinct life-cycle stages. The genome has been sequenced, and microarrays, RNA-interference and high-accuracy metabolomics are available. Furthermore, the availability of extensive kinetic data on all glycolytic enzymes has led to the early development of a complete, experiment-based dynamic model of an important biochemical pathway. Here we describe the achievements of trypanosome systems biology so far and outline the necessary steps towards the ambitious aim of creating a 'Silicon Trypanosome', a comprehensive, experiment-based, multi-scale mathematical model of trypanosome physiology. We expect that, in the long run, the quantitative modelling enabled by the Silicon Trypanosome will play a key role in selecting the most suitable targets for developing new anti-parasite drugs.
非洲锥虫已成为下一代系统生物学中极具潜力的单细胞模式生物。由于其相对简单、所有标准基因组学技术的可用性以及定量研究的悠久历史,它们具有独特的优势。存在可重现的培养方法,可用于形态和生理上不同的生命周期阶段。基因组已经测序,并且可以使用微阵列、RNA 干扰和高精度代谢组学。此外,广泛的糖酵解酶动力学数据的可用性导致了一个重要生化途径的完整、基于实验的动态模型的早期开发。在这里,我们描述了迄今为止锥虫系统生物学的成就,并概述了朝着创建“硅锥虫”这一雄心勃勃的目标迈出的必要步骤,即全面的、基于实验的、多尺度的锥虫生理学数学模型。我们预计,从长远来看,硅锥虫所实现的定量建模将在选择最适合开发新抗寄生虫药物的靶标方面发挥关键作用。