The role of CEACAM receptors in streptococcal infections

1.研究R28IgI3粘附素与CEACAM1受体相互作用的分子机制。评估B和r28是否诱导CEACAM1信号传导。为了明确CEACAM与GBS和GAS结合在上皮细胞中的作用，癌胚抗原相关黏附分子(CEACAM)受体表达于多种细胞，包括上皮细胞和白细胞。它们通过形成同嗜性和异嗜性相互作用来调节免疫反应，并作为几种人类病原体的对接部位。我们先前发现，人类链球菌可以高亲和力和高特异性地表达与人CEACAM受体结合的粘附素。这个项目将调查人类链球菌如何利用CEACAM受体来定植粘膜表面并引起侵袭性感染。我们将结合各种技术，包括生化技术和细胞感染分析。为了补充这一方法，我们将利用结构生物学方法来详细分析宿主与病原体的相互作用。由于链球菌仍然是一种重要的致病菌，目前还没有疫苗存在，因此对其毒力的研究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.