Living with uninvited guests - comparing plant and animal responses to endocytic invasions

与不速之客共处——比较植物和动物对内吞入侵的反应

• 批准号: BB/I004548/1
• 负责人: Vincent Jansen
• 金额: $ 89.75万
• 依托单位: Royal Holloway University of London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2010
• 资助国家: 英国
• 起止时间: 2010 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FI004548%2F1
• 关键词: Living; uninvited; guests; comparing; plant

Salmonella are Gram-negative bacterial pathogens capable of infecting a wide range of hosts, including humans, pigs, cows, chicken and even plants. Salmonella typhimurium is the causative agent of various human and animal diseases, reaching from enteritis to typhoid fever. According to the World Health Organisation, Salmonellosis is the most frequent food-borne disease with around 1,5 billion infections world-wide yearly. Although hygiene conditions have improved considerably, the number of Salmonella infections has increased over the last decade due to antimicrobial resistance and the ability of Salmonella to hide inside host cells. Novel approaches are needed to address this global health problem. Salmonella replicates within host cells in a membrane-bound compartment and is dependent on tolerance and resources of the host cell. To ensure survival and propagation, Salmonella therefore secretes proteins into the host cytoplasm using a type III secretion system. Some of the roles of these proteins are beginning to be revealed, in particular in modulating key host signal transduction pathways. However, to fully grasp the mechanisms of host-pathogen response, we need to take a system-wide view and determining the whole network of interactions between Salmonella proteins and the host proteins. Such deep insight will yield new approaches to target the pathogens. The identification of global networks of protein-protein interactions has been accelerated in recent years by the development of high-throughput technologies such as transcriptomics and proteomics. Here, we propose to identify protein-protein interactions and pathways as a means to understand the crosstalk between plant, animal or human hosts and Salmonella. By studying diverse hosts, we will address the following questions: How do different cells respond to bacterial invasion? To which subset of bacterial gene products are host cells exposed? Are there host 'weak points' that Salmonella exploits in animals and plant cells alike? We propose the idea that addressing these basic biological questions for divergent hosts such as plants and animals can help us elucidate the way the interaction between the host and the pathogen works at the mechanistic level. Analyzing the responses of different hosts to invasion, and integrating these results using a systems biology approach will expose the weaknesses and strengths in host responses. This will advance the field through the development of tools for the integration of data analysis, modelling and experimentation. In practical terms, this information can be exploited for drug development, diagnosis, disease forecasting, prevention and control. Our working hypothesis is that plants and animals respond to pathogen invasion in fundamentally similar ways, and that species-specificity is conferred by nuances on general themes. This means, that in principle, similar approaches should be applicable to design strategies to detect and fight Salmonella infections irrespective of host. We will test this hypothesis through an integrative cycle of computational and experimental approaches. The outcome will be either a unified model for the general host response, or separate models, one for each host. Thus, both, proving or disproving the hypothesis will be equally valuable.

沙门氏菌是革兰氏阴性细菌病原体，能够感染广泛的宿主，包括人类，猪，牛，鸡甚至植物。鼠伤寒沙门氏菌是各种人类和动物疾病的病原体，从肠炎到伤寒。根据世界卫生组织的数据，沙门氏菌病是最常见的食源性疾病，全球每年约有1,5亿人感染。虽然卫生条件有了很大改善，但在过去十年中，由于抗菌素耐药性和沙门氏菌隐藏在宿主细胞内的能力，沙门氏菌感染的数量有所增加。需要新的方法来解决这一全球健康问题。沙门氏菌在宿主细胞内的膜结合区室中复制，并且依赖于宿主细胞的耐受性和资源。为了确保存活和繁殖，沙门氏菌因此使用III型分泌系统将蛋白质分泌到宿主细胞质中。这些蛋白质的一些作用开始被揭示，特别是在调节关键的宿主信号转导途径。然而，为了完全掌握宿主-病原体反应的机制，我们需要采取系统范围的观点，并确定沙门氏菌蛋白质和宿主蛋白质之间的整个相互作用网络。这种深刻的见解将产生新的方法来靶向病原体。近年来，随着转录组学和蛋白质组学等高通量技术的发展，蛋白质-蛋白质相互作用的全球网络的识别已经加速。在这里，我们建议确定蛋白质-蛋白质相互作用和途径，以了解植物，动物或人类宿主和沙门氏菌之间的串扰。通过研究不同的宿主，我们将解决以下问题：不同的细胞如何应对细菌入侵？宿主细胞暴露于细菌基因产物的哪一个子集？沙门氏菌在动物和植物细胞中是否存在宿主的“弱点”？我们提出的想法，解决这些基本的生物学问题，不同的主机，如植物和动物，可以帮助我们阐明宿主和病原体之间的相互作用的机制水平。分析不同宿主对入侵的反应，并使用系统生物学方法整合这些结果将揭示宿主反应的弱点和优势。这将通过开发数据分析、建模和实验相结合的工具来推动该领域的发展。实际上，这些信息可用于药物开发、诊断、疾病预测、预防和控制。我们的工作假设是，植物和动物对病原体入侵的反应方式基本相似，物种特异性是由一般主题的细微差别赋予的。这意味着，在原则上，类似的方法应该适用于设计策略，以检测和对抗沙门氏菌感染，无论宿主如何。我们将通过计算和实验方法的综合循环来测试这一假设。结果将是针对一般宿主反应的统一模型，或针对每个宿主的单独模型。因此，证明或反驳这一假设都是同样有价值的。

项目成果

Population structure and associated phenotypes of Salmonella enterica serovars Derby and Mbandaka overlap with host range.

• DOI: 10.1186/s12866-016-0628-4
• 发表时间: 2016-02-04
• 期刊: BMC microbiology
• 影响因子: 4.2
• 作者: Hayward MR;Petrovska L;Jansen VA;Woodward MJ
• 通讯作者: Woodward MJ

Conformal predictors in early diagnostics of ovarian and breast cancers

• DOI: 10.1007/s13748-012-0021-y
• 发表时间: 2012-07
• 期刊: Progress in Artificial Intelligence
• 影响因子: 4.2
• 作者: Dmitry Devetyarov;I. Nouretdinov;Brian Burford;S. Camuzeaux;A. Gentry-Maharaj;A. Tiss;Celia J. Smith;Zhiyuan Luo;A. Chervonenkis;R. Hallett;V. Vovk;M. Waterfield;R. Cramer;J. Timms;J. Sinclair;U. Menon;I. Jacobs;A. Gammerman

Word usage mirrors community structure in the online social network Twitter

• DOI: 10.1140/epjds15
• 发表时间: 2013-12-01
• 期刊: EPJ DATA SCIENCE
• 影响因子: 3.6
• 作者: Bryden, John;Funk, Sebastian;Jansen, Vincent A. A.
• 通讯作者: Jansen, Vincent A. A.

Additional file 1: of Population structure and associated phenotypes of Salmonella enterica serovars Derby and Mbandaka overlap with host range

附加文件 1：肠道沙门氏菌血清型 Derby 和 Mbandaka 的种群结构和相关表型与宿主范围的重叠

• DOI: 10.6084/m9.figshare.c.3595598_d2
• 发表时间: 2016
• 作者: Hayward M

Additional file 2: of Population structure and associated phenotypes of Salmonella enterica serovars Derby and Mbandaka overlap with host range

附加文件 2：肠道沙门氏菌血清型 Derby 和 Mbandaka 的种群结构和相关表型与宿主范围的重叠

• DOI: 10.6084/m9.figshare.c.3595598_d1
• 发表时间: 2016
• 作者: Hayward M