Reprogramming of megakaryocytes and platelets in response to bacterial infection

与细菌感染作斗争仍然是当今人类面临的巨大挑战之一。研究人体对细菌负荷的反应为了解潜在机制、发明新的治疗策略和改善临床结果提供了重要的基础。因此，科学研究的重点往往从对经典免疫细胞（白细胞）功能的研究转向以前被低估的有助于抗菌宿主防御的细胞。这些细胞就是血小板，长期以来人们都知道它在止血中起着重要的作用。同时，一些新兴的研究表明血小板在免疫反应中起着重要的作用。尽管最近取得了这些进展，但对它们的前体细胞巨核细胞的调节作用的研究很少。该项目的核心问题是巨核细胞是否通过改变其基因表达谱来响应细菌感染，从而将改变的遗传密码转移到新释放的血小板上。为了回答这个问题，主办机构提供了大量常见和创新的分子生物学技术。我的初步研究将检测凝血因子III，组织因子的不同表达水平。一个细胞系模型（Meg-01’s）将与人类脐带血来源的巨核细胞并行使用。在随后的研究中，我将筛选在细菌感染期间失调的新的候选基因。从这个全球调查中选择的候选基因将被分析其基因表达谱和在巨核细胞和血小板中的功能，包括不同的细菌刺激如何诱导基因表达反应。该项目的结果将为巨核细胞和血小板的抗菌防御功能提供新的见解，并有可能确定管理传染病的新治疗方法。

The fight against bacterial infection is still one of the great challenges of mankind today. Investigating the body's response to bacterial burden provides an important basis to understand the underlying mechanisms, to invent new therapeutic strategies and to improve the clinical outcome. Thereby the scientific focus tends to switch from research on functions of classical immune cells, the leukocytes, to cells that were previously underestimated to contribute to antibacterial host defense. Such cells are platelets, which are long known for their substantial role in hemostasis. Meanwhile several emerging studies demonstrate that platelets are important players in immune responses. Despite these recent advances, there has been very little research on the regulatory role of their precursor cells, the megakaryocytes. The central question of this project is whether megakaryocytes respond to bacterial infection by changing their gene expression profile and thereby the transfer of an altered genetic code to newly released platelets. To answer this question, the host institution provides a plethora of common and innovative molecular biology techniques. My initial studies will examine different expression levels of the coagulation factor III, tissue factor. A cell line model (Meg-01's) will be used in parallel with human cord blood-derived megakaryocytes. In subsequent studies, I will screen for new candidate genes that are dysregulated during bacterial infection. Select candidates from this global inquiry will be analyzed for their gene expression profile and function in megakaryocytes and platelets including how different bacterial stimuli induce gene expression responses. The results of this project will provide novel insights into the antibacterial defense functions of megakaryocytes and platelets with the potential to identify new therapeutic approaches for managing infectious diseases.