Training in Systems Biology for the Study of Host-Pathogen Interactions

描述（由申请人提供）：我的长期目标是更好地了解粘膜上皮细胞识别感染起始的机制。口腔和口咽部的鳞状黏膜及相关组织作为主要入口，在共生生物的背景下与病原体相互作用，特别令人感兴趣。在这个为期六周的项目中，我的培训目标是学习将系统生物学概念分析应用于传染病起源的研究。为了实现这个目标，我将学习：在小鼠胃肠道感染模型中，询问先天DB中由关键突变调节的蛋白质相互作用网络（PINS）；和2。预测pin的轮毂，并进行实验验证。人类健康要求口腔和口咽入口将共生菌与病原体区分开来。我们实验室的证据表明，粘膜上皮细胞是主要的传感器，区分有害生物体和无害的共生定植体。此外，我们已经证明口腔上皮细胞可以被肠道病原体如李斯特菌和沙门氏菌侵袭，但这些细菌很少引起鳞状粘膜上皮的感染。相反，像牙龈卟啉单胞菌这样的口腔病原体会引起牙齿支撑结构的局部感染，但被吞咽却不会引起胃肠道感染。先天数据库是一个程序，允许可视化，询问和分析复杂的信号，发生在几乎任何组织，包括上皮，基于基因表达和蛋白质生产谱和策划，存档数据库的相关信息。通过了解口腔和口咽上皮细胞对局部病原体和短暂性肠道病原体的信号反应，我们可以设计更好的预防口腔和肠道感染的治疗方法。

DESCRIPTION (provided by applicant): My long term goal is to better understand the mechanisms used by mucosal epithelial cells to recognize the initiation of infections. The squamous mucosa of the oral cavity and oropharynx and related tissues are of particular interest as primary portals of entry and Interactions with pathogens in a background of commensal organisms. My training goal in this six week program is to learn to apply systems biology concepts analyses to the study of the initiation of infectious diseases. To foster this goal, I will learn to: 1. interrogate Innate DB for protein-interaction networks (PINS) that are modulated by key mutations engineered in a murine model of gastrointestinal infections; and 2. predict hubs of PINs, and validate experimentally. Human health requires that the oral and oropharyngeal portals distinguish commensals from pathogens. Evidence from our lab suggests that mucosal epithelial cells are primary sensors, distinguishing harmful organisms from harmless commensal colonizers. Furthermore, we have shown that oral epithelial cells can be invaded by enteric pathogens like Listeria and Salmonella, yet these bacteria rarely cause infections of the squamous mucosal epithelium. Conversely, oral pathogens like Porphyromonas gingivalis cause local infections of the supporting structures of the teeth, yet are swallowed but fail to cause infection'in the gastrointestinal tract. Innate DB is a program that permit visualization, interrogation and analysis of the complex signaling that occurs In virtually any tissue, including epithelia, based on gene expression and protein production profiles and curated, archived databases of relevant information. By understanding the signaling responses of the oral and oropharyngeal epithelia to the local pathogens and transient enteric pathogens, we can design better preventive therapies against oral and enteric infections.