Systems level analysis of animal metabolism by multicompartmental graph- and constraints-based modelling

通过基于多室图和约束的建模对动物代谢进行系统级分析

• 批准号: BB/F005342/1
• 负责人: Gavin Thomas
• 金额: $ 51.26万
• 依托单位: University of York
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2008
• 资助国家: 英国
• 起止时间: 2008 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FF005342%2F1
• 关键词: Systems; level; analysis; animal; metabolism

One goal of systems biology is to explain and predict how an organism works in terms of underlying processes (metabolism, gene expression patterns etc.). The purpose of this application is to design and construct systems-level models of metabolism in an animal comprising multiple organs with overlapping but appreciably different metabolic repertoires. Our core system is the pea aphid Acyrthosiphon pisum, which bears obligate intracellular bacteria Buchnera aphidicola in a specialized organ, the bacteriome. The bacteria and bacteriome are treated as metabolic compartments that interact with the gut, fat body (the principal insect organ of intermediary metabolism) and embryos (accounting for up to 75% of the total biomass of aphids) via the insect circulatory system. Our modelling, thereby, explores the integration of metabolic networks across multiple components comprising two distinct genomes within a single organism. We particularly address two challenges: (1) To develop new algorithms leading to a better understanding of the structure of metabolic networks, improved routes to explore the networks systematically for extracting functional information, and a grasp of how such networks have arisen. (2) To devise multi-compartment models, using flux balance analysis, to explore the metabolic organisation of animals. The modeling process follows a step-wise increase in complexity and realism of metabolic integration, building from our previous metabolic reconstruction of Buchnera. The final model seeks to define the fully interactive metabolic network comprising Buchnera-aphid interactions in maternal tissues and embryos. In parallel, our models will be made available for use by the wider community.

系统生物学的一个目标是解释和预测有机体是如何在潜在的过程（代谢，基因表达模式等）方面工作的。本应用程序的目的是设计和构建由多个器官组成的动物代谢系统级模型，这些器官具有重叠但明显不同的代谢功能。我们的核心系统是豌豆蚜虫Acyrthosiphon pisum，它在一个专门的器官，细菌组中承受专性细胞内细菌蚜虫Buchnera aphidicola。细菌和细菌组被视为代谢室，通过昆虫循环系统与肠道、脂肪体（中间代谢的主要昆虫器官）和胚胎（占蚜虫总生物量的75%）相互作用。因此，我们的模型探索了在单个生物体中包含两个不同基因组的多个组件的代谢网络的整合。我们特别解决了两个挑战：(1)开发新的算法，从而更好地理解代谢网络的结构，改进路线，系统地探索网络以提取功能信息，并掌握这些网络是如何产生的。(2)建立多室模型，利用通量平衡分析来探讨动物的代谢组织。建模过程遵循代谢整合的复杂性和现实性的逐步增加，建立在我们之前对Buchnera的代谢重建之上。最后的模型试图定义完全相互作用的代谢网络，包括布氏虫与蚜虫在母体组织和胚胎中的相互作用。同时，我们的模型将可供更广泛的社区使用。

项目成果

A fragile metabolic network adapted for cooperation in the symbiotic bacterium Buchnera aphidicola.

• DOI: 10.1186/1752-0509-3-24
• 发表时间: 2009-02-21
• 期刊: BMC systems biology
• 作者: Thomas GH;Zucker J;Macdonald SJ;Sorokin A;Goryanin I;Douglas AE
• 通讯作者: Douglas AE

Genome sequence of the pea aphid Acyrthosiphon pisum.

• DOI: 10.1371/journal.pbio.1000313
• 发表时间: 2010-02-23
• 期刊: PLoS biology
• 影响因子: 9.8
• 作者: International Aphid Genomics Consortium

Waste not, want not - nitrogen recycling by metabolic pathways shared between an animal and its symbiotic bacteria

不浪费，不想要——通过动物及其共生细菌之间共享的代谢途径进行氮回收

• 期刊: The Biochemist
• 作者: Gavin Hugh Thomas (Author)

The central role of the host cell in symbiotic nitrogen metabolism.

宿主细胞在共生氮代谢中的核心作用。

• DOI: 10.1098/rspb.2012.0414
• 发表时间: 2012
• 期刊: Proceedings. Biological sciences
• 作者: Macdonald SJ