Innate immune system function in the ctenophore Mnemiopsis leidyi

进化发育生物学的一个中心目标是了解不同的动物细胞类型是如何进化的。先天免疫系统包括免疫细胞和炎性分子，是抵御入侵病原体的第一道防线。免疫的出现，即识别自我与非自我的能力，是多细胞生命进化的组成部分。该项目使用最近开发的遗传技术来表征免疫细胞及其对模式栉水母中病原体的反应。栉水母，或称“梳水母”，是动物生命树中最古老的分支之一。该项目产生的数据将揭示动物免疫力的早期进化。该项目的外展部分包括为迈阿密戴德县的几所K-12学校开发一个基于细胞生物学的实践学习模块，这些学校为代表性不足和经济困难的学生提供服务。这个项目还包括一个指导研究实习迈阿密戴德社区学院的学生从代表性不足的群体。自我与非自我的识别，或免疫，是至关重要的多细胞的维护。关于非两侧对称动物的免疫系统生物学存在显着的知识差距。该项目旨在提高我们对动物先天免疫进化的理解，通过表征模型栉水母（Mnemiopsis leidyi）的免疫系统反应和免疫细胞特异性。该项目的目标包括：1）定义存在于拟记忆中的免疫细胞类型，2）通过批量和单细胞转录组学评估对离散免疫挑战的转录反应，以及3）使用CRISPR/Cas9基因组编辑确定转录因子干扰素调节因子（IRF）在免疫细胞发育/特化中的功能作用。该项目的实验结果将告知几个关键的悬而未决的问题有关的后生动物先天免疫。问题1：栉水母中与先天免疫相关的细胞类型的范围是否反映了动物干细胞谱系中免疫细胞类型多样性的早期建立和多样化？在免疫细胞发育和对微生物病原体的先天免疫应答过程中，栉水母中的免疫细胞是否利用保守或不同的基因表达网络？问题3：与拟记忆虫中的免疫细胞相关的新特征是否反映了它们对首选河口/沿海环境中存在的病原体的独特适应？这项工作将揭示与后生动物先天免疫进化相关的病原体防御机制和免疫细胞特异性的保守方面，并揭示病原体防御和免疫细胞类型多样性的潜在新的栉水母特异性方面。该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估来支持。

A central goal in evolutionary developmental biology is to understand how diverse animal cell types have evolved. The innate immune system, which includes immune cells and inflammatory molecules, represents the first line of defense against invading pathogens. The emergence of immunity, the ability to recognize self vs nonself, is integral to the evolution of multicellular life. This project uses recently developed genetic techniques to characterize immune cells and their responses to pathogens in a model ctenophore. The ctenophores, or ”comb jellies,” represent one of the most ancient branches of the animal tree of life. The data produced by this project will shed light on the early evolution of immunity in animals. Outreach components of this project include the development of a hands-on cell biology based learning module for several Miami-Dade County K-12 schools that serve underrepresented and economically disadvantaged students. This project also includes a mentored research internship for Miami-Dade Community College students from underrepresented groups.The recognition of self vs nonself, or immunity, is critical to the maintenance of multicellularity. A significant knowledge gap exists regarding immune system biology in non-bilaterian animals. This project seeks to improve our understanding of innate immunity evolution in animals by characterizing both immune system response and immune cell specification in the model ctenophore, Mnemiopsis leidyi. The goals of this project include: 1) defining immune cell types present in Mnemiopsis, 2) assessing transcriptional responses to discrete immune challenges through both bulk and single-cell transcriptomics, and 3) determining the functional role of the transcription factor Interferon Regulatory Factor (IRF) in immune cell development/specification using CRISPR/Cas9 genome editing. This project's experimental results will inform several critical outstanding questions relating to metazoan innate immunity. Q1) Does the range of cell types associated with innate immunity in ctenophores reflect an early establishment and diversification of immune cell type diversity in the animal stem lineage? Q2) Do immune cells in ctenophores utilize conserved or divergent networks of gene expression both during immune cell development and innate immunity responses to microbial pathogens? Q3) Do novel traits associated with immune cells in Mnemiopsis reflect unique adaptations to pathogens present in their preferred estuary/coastal environments? This work will reveal conserved aspects of pathogen defense mechanisms and immune cell specification associated with the evolution of metazoan innate immunity and reveal potential novel ctenophore-specific aspects of pathogen defense and immune cell type diversity.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.