Comparative biology of phagocyte antimicrobial responses

吞噬细胞抗菌反应的比较生物学

• 批准号: 355303-2013
• 负责人: Barreda, Daniel
• 金额: $ 2.91万
• 依托单位: University of Alberta
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=572556
• 关键词: Comparative; biology; phagocyte; antimicrobial; responses

My laboratory is interested in the evolution of white blood cell immune defense mechanisms. Specifically, we focus on the balance between pro-inflammatory and homeostatic responses at an infection site because of its relevance to host immunocompetence and disease prevention. Characterization of well-conserved pathways offers important evolutionary context for generation of the complex immune networks that now exist in higher vertebrates. Moreover, characterization of more recently developed features may help identify vulnerability gaps for pathogen infiltration, or which contribute to unwanted immune reactions (e.g. autoimmunity). During the first installment of my NSERC Discovery program (2008-2012) my lab took significant strides towards the establishment of unique analytical protocols for functional characterization of cellular antimicrobial responses. Side-by-side comparisons of animal models that span large evolutionary distances required that we established transferable tools that help overcome a continued lag in reagent availability (e.g antibody markers). We have begun to make significant contributions to the field, as evidenced by recent publications in Dev Comp Immunol, PLoS ONE and J Leuk Biol (cover article). Herein, I propose to use a combined molecular and cell biology approach that employs animal models and cell culture techniques to further dissect the evolving roles of phagocytes in the control of inflammation. Specifically, we will focus on two aims: 1) to examine the evolution and contributions of neutrophil phagocytosis to the control of inflammation, and 2)to define the role a novel soluble form of the CSF-1 receptor as an effective regulator of inflammation across evolution. All major techniques, infrastructure, and a strong core of trainees are already in place in my lab, and are further supported through university facilities and collaborators. Our results have positive implications for the fundamental understanding of inflammation, may open new doors for the prevention of undesirable autoimmune or chronic inflammatory conditions, and offer novel opportunities for the control of fish diseases in commercial aquaculture systems.

我的实验室对白色血细胞免疫防御机制的进化很感兴趣。具体来说，我们专注于在感染部位的促炎和稳态反应之间的平衡，因为它与宿主免疫能力和疾病预防有关。对高度保守的免疫通路的研究为高等脊椎动物中复杂免疫网络的形成提供了重要的进化背景。此外，表征最近开发的功能可能有助于识别病原体渗透的脆弱性缺口，或有助于不必要的免疫反应（例如自身免疫）。在我的NSERC发现计划的第一部分（2008-2012）期间，我的实验室在建立用于细胞抗菌反应功能表征的独特分析方案方面取得了重大进展。跨越大进化距离的动物模型的并排比较要求我们建立可转移的工具，以帮助克服试剂可用性（例如抗体标记物）的持续滞后。我们已经开始对该领域做出重大贡献，最近在Dev Comp Immunol，PLoS ONE和J勒克Biol（封面文章）上发表的文章证明了这一点。在此，我建议使用一个结合的分子和细胞生物学的方法，采用动物模型和细胞培养技术，进一步剖析吞噬细胞在炎症控制中的作用。具体来说，我们将专注于两个目标：1）检查中性粒细胞吞噬作用对炎症控制的演变和贡献，以及2）定义CSF-1受体的新型可溶性形式作为整个进化过程中炎症的有效调节剂的作用。所有主要的技术，基础设施和强大的核心受训人员已经在我的实验室，并通过大学设施和合作者进一步支持。我们的研究结果对炎症的基本理解具有积极意义，可能为预防不良自身免疫或慢性炎症疾病打开新的大门，并为商业水产养殖系统中的鱼类疾病控制提供新的机会。