Mechanisms of neural Toll-like Receptor 4-signaling

toll样受体4 （TLR4）信号在神经干细胞的调控中起重要作用，包括调节其增殖和分化。在这个项目的框架内，我们将应用最先进的干细胞生物学方法以及单分子和超分辨率显微镜来解决与不同外源性和内源性配体有关的神经细胞系和神经干细胞中tlr4激活和信号传导的基本问题。我们将使用基于细胞的筛选系统分析所提出的内源性蛋白质配体的生物活性，通过TLR4验证其排他作用，并将其与不同的脂多糖配体进行比较。我们将利用定量单分子超分辨率成像技术研究不同脂多糖和内源性配体处理后的受体动力学和信号体的组成。此外，我们将研究不同的配体如何影响神经细胞系和神经干细胞的增殖、迁移和分化。我们的目标是推导出完整细胞质膜上TLR4激活的机制图。

Toll-like receptor 4 (TLR4) -signaling plays an important role in regulation of neural stem cells, including modulation of their proliferation and differentiation. In the frame of this project we will apply state-of-the-art stem cell biology methods together with single-molecule and super-resolution microscopy to address fundamental questions on TLR4-activation and signaling in neural cell lines and neural stem cells in relation to different exogenous and endogenous ligands. We will analyze the biological activity of proposed endogenous protein ligands using a cell-based screening system, validate the exclusive action through TLR4, and compare them to different lipopolysaccharide ligands.We will study the receptor dynamics and the composition of the signalosome upon treatment with different lipopolysaccharides and proposed endogenous ligands using quantitative single-molecule super-resolution imaging. Moreover, we will investigate how different ligands impact proliferation, migration and differentiation of neural cell lines and neural stem cells. We aim to derive a mechanistic picture on the activation of TLR4 at the plasma membrane of intact cells.