Understanding how pollutant aerosol particulates impact airway inflammation

了解污染物气溶胶颗粒如何影响气道炎症

• 批准号: 2881629
• 金额: --
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2027
• 资助国家: 英国
• 起止时间: 2027 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2881629
• 关键词: Understanding; how; pollutant; aerosol; particulates

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.

接触颗粒物 (PM) 会导致呼吸系统疾病，其影响主要来自生命早期的接触，但我们对其潜在的免疫机制知之甚少。越来越多的证据表明“先天印记”过程，即先前的炎症改变随后的反应并加剧炎症。这对于婴儿发育以及随后对感染和过敏的反应尤其成问题。该项目将开发一系列颗粒物，以探索细胞对 PM 气溶胶的反应和气道炎症中的先天印记。该提案将生物信息学分析与体外和体内方法相结合，以确定细胞对 PM 的反应。目标 1：开发一个特性良好的模拟环境颗粒面板，包括柴油燃烧颗粒（可通过合作伙伴提供）以及实验室中已使用的精选颗粒。 -将在与模拟肺液混合之前和之后以及在暴露相关条件下对颗粒物的物理化学特性进行表征，以便在博士项目的后续阶段中表征颗粒物并提供准确的剂量表示目标2：评估上皮细胞和巨噬细胞的反应使用模拟环境颗粒面板进行初级和次级刺激。-这将通过评估颗粒与细胞的关联和摄取（TEM、光学显微镜）、细胞活力以及通过 qPCR、细胞计数等产生免疫效应物来实现检查细胞损伤/激活/反应的不同途径。目标 3：检查早期生命体内对肺内气溶胶污染物的反应。 -生命的第一阶段是免疫系统发育的关键时期，对环境暴露高度敏感。新生小鼠肺部将暴露于不同性质的PM，并在以后的生活中检查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影响，包括先天记忆。这主要将在合作机构中完成。该项目是气溶胶科学 EPSRC 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，同时发展他们的能力博士研究提案。学生还可以访问在线培训门户，在那里他们可以听迷你讲座并解决多项选择问题。他们还将参加课堂培训，以他们在培训过程中学到的科学为基础，解决更复杂的研究问题。