Understanding how pollutant aerosol particulates impact airway inflammation

暴露于颗粒物（PM）有助于呼吸系统疾病的主要影响来自早期的生活暴露，但我们知道的基本免疫机制很少。越来越多的证据暗示了一个“先天印记”的过程，即先前的炎症改变了随后的反应并增加了炎症。这对于婴儿发育和随后对感染和过敏的反应尤其成问题。本计画将开发一系列的微粒，以探讨细胞对PM气溶胶的反应及气道发炎中的固有印记，本计画将联合收割机结合生物资讯学分析与体内外方法，以定义细胞对PM的反应。目标1：开发一个充分表征的模拟环境颗粒面板，包括柴油燃烧颗粒（可通过合作伙伴获得）和一系列已在实验室中使用的颗粒。- 颗粒的物理化学性质将在与模拟肺液混合之前和之后以及在呼吸相关的条件下进行表征，以便识别颗粒并在博士项目的后续阶段提供准确的剂量表示目的2：评估上皮细胞和巨噬细胞对模拟环境颗粒面板的初级和次级刺激的反应。这将通过评估颗粒与细胞的结合和摄取（TEM，光学显微镜）、细胞活力和通过qPCR、细胞计数等产生的免疫效应物以及检查细胞损伤/活化/应答的不同途径来实现。- 生命的第一阶段是免疫系统发育的关键时期，并且对环境暴露高度敏感。新生小鼠肺将暴露于不同性质的PM，并检查其在以后的生活中对生物气溶胶的炎症反应。将使用流式细胞术、组织化学和mRNA测序等方法评估炎症和毒理学效应，包括先天记忆。该项目是EPSRC气溶胶科学CDT的一部分，学生将获得核心气溶胶科学背景，研究方法，编程技能以及专业精神和知识翻译的培训，同时制定博士研究计划。学生还可以访问在线培训门户网站，在那里他们可以听迷你讲座并解决多项选择题。他们还将参加课堂培训，以解决他们在培训过程中学到的科学所支持的更复杂的研究问题。

Exposure to particulate matter (PM) contributes to respiratory diseases with major impacts from early life exposure yet we know little of the underlying immunological mechanisms. Increasing evidence implicates a process of "innate imprinting" whereby prior inflammation alters subsequent responses and increases inflammation. This is particularly problematic for infant development and subsequent responses to infection and allergy. This project will develop a range of particulates in order to explore the cellular response to PM aerosols and innate imprinting in airway inflammation.This proposal will combine bioinformatics analysis with in vitro and in vivo methods to define the cellular response to PM. Aim 1: Development of a well-characterized simulated environmental particulate panel including diesel combustion particles (available through partner) and of a selection of particles already used in the labs. -Physical-chemical properties of particulates will be characterised prior to and after mixing with simulated lung fluid and in exposure-relevant conditions in order to characterise particulate and inform accurate dose representation in the subsequent stages of the PhD projectAim 2: Assess epithelial and macrophage responses to primary and secondary stimulation with simulated environmental particulate panel.-This will be achieved by assessing association and uptake of particulate to cells (TEM, light microscopy), cell viability, and production of immune effectors by qPCR, cytometry etc and examination of differential pathways of cell damage/activation/response.Aim 3: To examine early life in vivo responses to aerosol pollutants within the lung. -The first stages of life are a critical time for development of the immune system and are highly sensitive to environmental exposures. Neonatal mouse lungs will be exposed to PM of different properties and examined for inflammatory responses to biological aerosols in later life. Inflammatory and toxicological effects including innate memory will be assessed using flow cytometric, histochemical and mRNA sequencing among other methods. This will largely be done in the partner institution.This project is part of the EPSRC CDT in aerosol science and the student will get training in core aerosol science background, research methods, programming skills, as well as professionalism and knowledge translation, while developing their PhD research proposals. Students will also have access to an online training portal where they can listen to mini lectures and solve multiple choice problems. They will also attend in class training solving more complex research problems underpinned by the science they have learned during the course of their training.