In Silico Modelling of Toll-Like Receptor Pathways in Human Epidermal Keratinocytes

人表皮角质形成细胞中 Toll 样受体通路的计算机模拟

• 批准号: 2137542
• 金额: --
• 依托单位: University of Southampton
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2137542
• 关键词: Silico; Modelling; Toll; Like; Receptor

The discovery, that the epithelial surfaces, such as skin, can actively programme systemic immune responses has revolutionized our understanding of human immunity. To fully harness this exciting finding, it is essential to dissect the molecular interactions orchestrating the process of immune programming. Our recent research identified the key molecular networks regulating antigen presentation by human skin immune cells, and documented the power of stochastic modelling for prediction of different functional immunity outcomes (Polak et al, 2017, Nature: Scientific Reports 7:668; Livigni et al Nature Protocols, 2018, in press).The aim of this PhD project is to identify, reconstruct, and model in vitro and in silico, gene regulatory networks of host-pathogen interactions in human skin, developing a novel platform for in silico investigation of immunity.Specific objectives:1. Identification of molecular networks in human skin.2. Assembling of an in silico representation of the key gene regulatory network.3. Dynamic modelling of the in silico model to investigate immune responses in human intact epidermis.4. Targeting human keratinocytes to modulate function.

皮肤等上皮表面可以主动规划全身免疫反应，这一发现彻底改变了我们对人类免疫的理解。为了充分利用这一令人兴奋的发现，分析协调免疫编程过程的分子相互作用是必不可少的。我们最近的研究发现了调节人类皮肤免疫细胞抗原提呈的关键分子网络，并证明了随机建模对不同功能免疫结果的预测能力(Polak等，2017，自然：科学报告7：668；Livigni等自然协议，2018，出版)。本博士项目的目的是在体外和电子计算机中识别、重建和模拟人体皮肤宿主-病原体相互作用的基因调控网络，为免疫的电子研究开发一个新的平台。具体目标：1.识别人类皮肤的分子网络。关键基因调控网络的电子表达组装。研究人体完整表皮免疫反应的电子计算机模型的动态模拟。靶向人类角质形成细胞以调节功能。