A mathematical and biophysical analysis of salmonella macrophage interactions

沙门氏菌巨噬细胞相互作用的数学和生物物理分析

• 批准号: BB/H021930/1
• 负责人: Clare Bryant
• 金额: $ 32.49万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Fellowship
• 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%2FH021930%2F1
• 关键词: mathematical; biophysical; analysis; salmonella; macrophage

Salmonella enterica causes a wide range of diseases in many animals. Economic losses to the farming industry through Salmonella infection are potentially very high, but also important is the fact that a number of serovars that infect animals can also cause food poisoning and gastroenteritis in humans. Salmonella infect specialised immune cells (macrophages) where the bacteria reside within an intracellular compartment called the salmonella-containing vacuole. Within the macrophage the bacteria may be killed, may hide, may grow and can cause the cell to die. The interaction between macrophages and salmonellae is critically important to the progression of disease. Controlling the numbers of bacteria within the macrophage is an important step in enabling the host to stop the bacteria growing and to survive infection. Many mechanisms involved in the interaction between Salmonella and macrophages are unclear. In particular little is known about how the macrophage physically interacts with the cell. The macrophage detects the presence of bacteria through specialised proteins called Pattern Recognition Receptors (PRRs) which induce macrophage responses to help the host control a salmonella infection. In this project I will use mathematical models to predict how PRR activity effects the process by which Salmonella infect macrophages and then test these theoretical assumptions using biological experiments. I will use physical techniques to investigate whether PRRs influence how Salmonella associate with macrophages. In the final part of the project I will compare how PRR activity affects the global response of macrophages to infection. This project will increase our understanding of how Salmonella infect macrophages and may deliver new targets for developing drugs to treat the diseases caused by these pathogens.

肠沙门氏菌在许多动物中引起广泛的疾病。通过沙门氏菌感染给农业行业的经济损失可能很高，但同样重要的是，许多感染动物的血清射手也可能引起人类食物中毒和胃肠炎。沙门氏菌感染专门的免疫细胞（巨噬细胞），其中细菌位于称为含沙门氏菌的液泡的细胞内室内。在巨噬细胞中，细菌可能被杀死，可能藏起来，可能生长并可能导致细胞死亡。巨噬细胞与沙门氏菌之间的相互作用对疾病的发展至关重要。控制巨噬细胞内的细菌数量是使宿主阻止细菌生长并生存感染的重要步骤。沙门氏菌与巨噬细胞之间相互作用涉及的许多机制尚不清楚。特别是关于巨噬细胞如何与细胞物理相互作用的知之甚少。巨噬细胞通过称为模式识别受体（PRRS）的专门蛋白质检测细菌的存在，该蛋白会诱导巨噬细胞反应以帮助宿主控制沙门氏菌感染。在这个项目中，我将使用数学模型来预测PRR活性如何影响沙门氏菌感染巨噬细胞，然后使用生物学实验测试这些理论假设。我将使用物理技术研究PRR是否影响沙门氏菌如何与巨噬细胞缔合。在项目的最后部分，我将比较PRR活动如何影响巨噬细胞对感染的全球反应。该项目将增加我们对沙门氏菌感染巨噬细胞的理解，并可能为开发药物提供新的靶标，以治疗这些病原体引起的疾病。

项目成果

Assessing the Collective Dynamics of Motile Cilia in Cultures of Human Airway Cells by Multiscale DDM

通过多尺度 DDM 评估人气道细胞培养物中活动纤毛的集体动态

• DOI: 10.17863/cam.12719
• 发表时间: 2017
• 作者: Feriani L

Criticality of plasma membrane lipids reflects activation state of macrophage cells

质膜脂质的临界程度反映了巨噬细胞的激活状态

• DOI: 10.1101/680157
• 发表时间: 2019
• 作者: Cammarota E

The frequency and duration of Salmonella-macrophage adhesion events determines infection efficiency.

• DOI: 10.1098/rstb.2014.0033
• 发表时间: 2015-02-05
• 期刊: Philosophical transactions of the Royal Society of London. Series B, Biological sciences
• 作者: Achouri S;Wright JA;Evans L;Macleod C;Fraser G;Cicuta P;Bryant CE
• 通讯作者: Bryant CE

Dynamics of Salmonella infection of macrophages at the single cell level.

• DOI: 10.1098/rsif.2012.0163
• 发表时间: 2012-10-07
• 期刊: Journal of the Royal Society, Interface
• 作者: Gog JR;Murcia A;Osterman N;Restif O;McKinley TJ;Sheppard M;Achouri S;Wei B;Mastroeni P;Wood JL;Maskell DJ;Cicuta P;Bryant CE
• 通讯作者: Bryant CE