Witkamp R F
TNO Pharma, Zeist, The Netherlands.
J Vet Pharmacol Ther. 2005 Jun;28(3):235-45. doi: 10.1111/j.1365-2885.2005.00662.x.
This review discusses some of the recent developments in genomics and its current and future relevance for veterinary pharmacology and toxicology. With the rapid progress made in this field several new approaches in pharmacological and toxicological research have developed and drug discovery and drug development strategies have changed dramatically. In this review, the term genomics is used to encompass the three sub-disciplines transcriptomics, proteomics and metabolomics (or metabonomics) to describe the formation and fate of mRNA, proteins and metabolites, respectively. The current status and methods of the technology and some applications are briefly described. Although the DNA sequencing programmes are receiving considerable attention, the real value of genomics for pharmacology and toxicology is brought by the parallel developments in bio-informatics, bio-statistics and the integration of biology with mathematics and information technology. The ultimate level of integration is now mostly called systems biology, where mRNA, proteins and metabolites are being analysed in parallel, using a complete arsenal of analytical techniques (DNA-array, LC-MS/MS, GC-MS/MS, NMR, etc.). The information thus collected is analysed, integrated, linked to database information and translated to pathways and systems. This approach offers an enormous potential to study disease mechanisms and find new drug targets. Thus far, genomics and systems biology have not been introduced significantly in typical veterinary pharmacological and toxicological research programmes. The high costs and complexity connected to these large projects often form major obstacles for research groups with limited budgets. In other veterinary areas and disciplines, including infectious diseases, animal production and food-safety more examples of application are available. Genomics and bio-informatics provide outstanding opportunities to study pharmacology and toxicology in a more holistic way, taking into account the complexity of biological systems and based on the basic principles of physiology and the concept of homeostasis. Knowledge of biology, in vivo and in vitro models, and comparative pharmacology/toxicology is essential here, creating excellent opportunities for the veterinary trained scientist.
本综述讨论了基因组学的一些最新进展及其对兽医药理学和毒理学的当前及未来意义。随着该领域的迅速发展,药理学和毒理学研究出现了几种新方法,药物发现和药物开发策略也发生了巨大变化。在本综述中,“基因组学”一词用于涵盖三个子学科——转录组学、蛋白质组学和代谢组学(或代谢物组学),分别描述mRNA、蛋白质和代谢物的形成和命运。本文简要描述了该技术的现状、方法及一些应用。尽管DNA测序计划备受关注,但基因组学对药理学和毒理学的真正价值来自于生物信息学、生物统计学以及生物学与数学和信息技术整合的并行发展。现在,整合的最终阶段大多被称为系统生物学,其中使用一整套分析技术(DNA芯片、液相色谱-串联质谱、气相色谱-串联质谱、核磁共振等)对mRNA、蛋白质和代谢物进行并行分析。由此收集的信息经过分析、整合,与数据库信息相链接,并转化为通路和系统。这种方法为研究疾病机制和寻找新的药物靶点提供了巨大潜力。到目前为止,基因组学和系统生物学在典型的兽医药理学和毒理学研究项目中尚未得到显著应用。与这些大型项目相关的高成本和复杂性常常给预算有限的研究团队构成主要障碍。在其他兽医领域和学科,包括传染病、动物生产和食品安全方面,有更多的应用实例。基因组学和生物信息学提供了绝佳机会,以更全面的方式研究药理学和毒理学,考虑到生物系统的复杂性,并基于生理学基本原理和稳态概念。这里,体内和体外模型的生物学知识以及比较药理学/毒理学知识至关重要,为受过兽医培训的科学家创造了绝佳机会。