The role of CEACAM receptors in streptococcal infections

1. 表征R28IgI3粘附素与CEACAM1受体相互作用的分子机制2。评估B和R28是否诱导CEACAM1信号3。为了确定CEACAM在上皮细胞背景下与GBS和GAS结合的功能，scarcino胚胎抗原相关粘附分子（CEACAM）受体在包括上皮细胞和白细胞在内的广泛细胞上表达。它们通过形成亲同性和亲异性的相互作用来调节免疫反应，并作为几种人类病原体的对接位点。我们之前发现，人链球菌病原体可以表达高亲和力和高特异性结合人CEACAM受体的粘附素。本项目将研究人类链球菌病原体如何利用CEACAM受体在粘膜表面定植并引起侵袭性感染。我们将结合各种技术，包括生化技术和细胞感染分析。为了补充这种方法，我们将利用结构生物学方法来分析宿主-病原体相互作用的分子细节。由于链球菌病原体仍然是重要的，目前没有疫苗，研究其毒力对于开发新的治疗策略具有重要意义。

1. To characterise the molecular mechanism of the R28IgI3 adhesin and CEACAM1 receptor interaction2. To assess whether B and R28 induce CEACAM1 signalling3. To define the function of CEACAM engagement with GBS and GAS in the context of epithelial cellsCarcinoembryonic antigen-related adhesion molecules (CEACAM) receptors are expressed on wide range of cells including epithelial cells and leukocytes. They modulate immune responses through forming homophilic and heterophilic interactions, and serve as docking sites for several human pathogens. We previously discovered that human streptococcal pathogens can express adhesins that bind human CEACAM receptors with high-affinity and high-specificity. This project will investigate how human streptococcal pathogens utilise CEACAM receptors to colonise mucosal surfaces and to cause invasive infections. We will combine various techniques including biochemical techniques and cellular infection assays. To complement this approach, we will utilise structural biology approaches to analyse host-pathogen interactions in molecular detail. As Streptococcal pathogens remain a significant and no vaccines currently exist, research into their virulence is of importance for development of novel therapeutic strategies.