Comparative biology of phagocyte antimicrobial responses

我的实验室对白细胞免疫防御机制的进化很感兴趣。具体地说，我们关注感染部位的促炎反应和动态平衡反应之间的平衡，因为它与宿主免疫能力和疾病预防有关。对保守途径的描述为高等脊椎动物中复杂免疫网络的产生提供了重要的进化背景。此外，对最近开发的特征的表征可能有助于识别病原体渗透的脆弱性缺口，或有助于导致不必要的免疫反应(例如自身免疫)的脆弱性缺口。在我的NSERC发现计划的第一期(2008-2012)，我的实验室在建立独特的分析方案方面取得了重大进展，用于细胞抗菌反应的功能表征。对跨越大进化距离的动物模型进行并排比较需要我们建立可移植的工具，帮助克服试剂可用性的持续滞后(例如抗体标记物)。我们已经开始在这一领域做出重大贡献，最近发表在Dev Comp免疫、PLoS One和J Leuk Biol(封面文章)上的文章就证明了这一点。在这里，我建议使用分子和细胞生物学相结合的方法，利用动物模型和细胞培养技术来进一步剖析吞噬细胞在炎症控制中的不断演变的作用。具体地说，我们将集中于两个目标：1)研究中性粒细胞吞噬作用在炎症控制中的进化和贡献；2)确定一种新的可溶性形式的CSF-1受体作为炎症的有效调节因子在整个进化过程中的作用。所有的主要技术、基础设施和强大的学员核心都已经在我的实验室中到位，并得到大学设施和合作者的进一步支持。我们的结果对于从根本上理解炎症有积极的意义，可能会为预防不良的自身免疫或慢性炎症打开新的大门，并为商业水产养殖系统中的鱼类疾病控制提供新的机会。

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.