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。包括免疫细胞和炎症分子在内的先天免疫系统是抵御入侵病原体的第一道防线。免疫的出现，即识别自我与非我的能力，是多细胞生命进化不可或缺的一部分。该项目使用最近发展的遗传技术来表征免疫细胞及其对病原体的反应。纤毛虫，或称“梳状水母”，代表了生命之树上最古老的分支之一。该项目产生的数据将为动物免疫的早期进化提供线索。该项目的外展部分包括为迈阿密-戴德县的几所K-12学校开发基于实践细胞生物学的学习模块，这些学校为代表性不足和经济困难的学生提供服务。该项目还包括为来自代表性不足群体的迈阿密-戴德社区学院的学生进行的有指导的研究实习。对自我与非我的认识，或免疫力，对维持多细胞至关重要。在非双边动物的免疫系统生物学方面，存在着显著的知识差距。这个项目试图通过描述动物的免疫系统反应和免疫细胞特性来提高我们对动物先天免疫进化的理解。该项目的目标包括：1)确定免疫细胞类型，2)通过批量和单细胞转录，评估对离散免疫挑战的转录反应，以及3)利用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/规范中的功能作用。该项目的实验结果将提供有关后生动物天然免疫的几个关键悬而未决的问题。问题1)与先天性免疫相关的细胞类型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？Q2)在免疫细胞发育和对微生物病原体的先天免疫反应过程中，鞭毛虫中的免疫细胞是否利用保守或分化的基因表达网络？问题3)与免疫细胞相关的新特征是否反映了对其偏好的河口/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规范的保守方面，并揭示病原体防御和免疫细胞类型多样性的潜在新的Cenopore特定方面。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.