Dynamic imaging of intracellular signaling pathways during infections of human epithelia

我实验室的研究兴趣是了解细胞如何感知环境的变化，并对这些变化做出适当的反应。这种感知与反应的耦合被称为信号转导，因为它涉及将细胞感知到的信息传递给参与细胞活动的机器。这些信号通过各种各样的方式传递，对它们的研究对于正确理解细胞功能至关重要。我对病原体遇到目标宿主细胞时产生的反应特别感兴趣。上皮细胞是排列在我们身体上的组织，在我们的内部器官和周围环境之间形成物理屏障。作为人类，我们的整个生命都在与无数的微生物接触中度过，上皮在保护我们免受有害病原体的侵害方面起着关键作用。在本研究中，我们将研究五种上皮（皮肤、肺、肠、肾和宫颈）对机会性病原体金黄色葡萄球菌的反应差异，以了解宿主-病原体相互作用中信号转导的基本机制。这些信号的性质将根据一些参数如强度、持续时间和振幅而变化，这些参数对于使用有限数量的分子产生不同细胞活动所需的特异性都是必不可少的。信号转导的大多数研究都是基于终点分析，因此很难评估上述参数的重要性。因此，我们建议开发关键细胞内通路的荧光标记，以动态测量上皮细胞暴露于金黄色葡萄球菌后它们的激活。综上所述，我们希望能更好地理解上皮细胞启动宿主反应感知感染的基本机制。

The research interest of my laboratory is to understand how cells perceive changes in their environment and elaborate an appropriate response to these changes. The coupling of this perception to a response is termed signal transduction, as it involved the transmission of the information perceived by the cell to machineries involved in cellular activities. These signals are transmitted via a wide variety of means and their study is essential to properly understand cell functions. I'm particularly interested in the response generated by a pathogen when it meets a target host cell. Epithelia are tissues that lined our body forming a physical barrier between our inner organs and the surrounding environment. Our entire life as humans is spent in contact with countless microorganisms, and the epithelium plays a key role in protecting us from harmful pathogens. In this proposal we will look at the differences in response of five epithelia (skin, lung, intestine, kidney and cervix) to an opportunistic pathogen, the bacteria Staphylococcus aureus to understand the fundamental mechanisms of signal transduction in the host-pathogen interaction. The nature of these signals will vary according to a number of parameters like strength, duration and amplitude, which are all essential in giving rise to the specificity needed for different cellular activities using a finite number of molecules. The majority of studies in signal transduction are based on end-point assays, from which it is difficult to evaluate the importance of the aforementioned parameters. Therefore we are proposing to develop fluorescent markers of key intracellular pathways to dynamically measure their activation following the exposure of epithelial cells to S. aureus. Taken together we hope to better understand the fundamental mechanisms of perception of an infection by the epithelium initiating the host response.