Spatiotemporal analysis of gene regulatory programs associated with GBS infection during pregnancy

妊娠期GBS感染相关基因调控程序的时空分析

基本信息

批准号：
10509389
负责人：
Adam Jonathan Ratner
金额：
$ 73.4万
依托单位：
NEW YORK UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-11-09 至 2024-10-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10509389
关键词：
Adult Architecture Birth Cells Data Analyses Development Event Fetal Development Gene Expression Gene Expression Profile Gene Expression Regulation Genes Genetic Transcription Genome Genomics Goals Human Immune response Infection Intervention Knock-out Macrophage Measures Methods Modeling Molecular Morbidity - disease rate Pathogenesis Placenta Pregnancy Premature Birth Process RNA Regulator Genes Reporting Research Resolution Serotyping Site Streptococcal Infections Streptococcus Group B Study models System Testing Time Transcriptional Regulation experience fetal fetal infection gastrointestinal in vivo Model innovation insight intraamniotic infection mortality mouse model neonatal infection neonatal sepsis novel pathogen placental infection postnatal period programs response single cell analysis single-cell RNA sequencing spatial integration spatiotemporal tool transcriptome transcriptome sequencing transcriptomics vaginal mucosa

项目摘要

PROJECT SUMMARY Infection during pregnancy or in the immediate postnatal period is associated with substantial morbidity and mortality worldwide. Group B Streptococcus (GBS) is a major cause of chorioamnionitis (CAM) and neonatal sepsis. The placenta acts as the initial interface between GBS and the host immune response during chorioamnionitis, constituting the locus of host-pathogen interaction. Current understanding of the pathogenesis of CAM has been limited by a lack of tools revealing the spatial and temporal components of placental infection. Specifically, we lack an understanding of how the infection unfolds over time and across the placental architecture. Breakthroughs in single-cell genomics and spatial transcriptomics now enable the unbiased and systematic analysis of the process of infection. Here we propose to apply these methods to GBS infection of the placenta: examining host-specific responses, the host-pathogen interface, and perturbations of the GBS infection program. In Aim 1 we will combine spatial transcriptomics and single-cell RNA-Seq to study the progression of GBS infection in a novel murine model of ascending infection and CAM. In Aim 2 we will simultaneously study host and pathogen gene expression programs during infection in primary human placental macrophages. In Aim 3 we will test a conceptual model of GBS infection by systematically assessing the effect of targeted deletions of specific GBS genes. Integrating these approaches will provide a rich view of host-pathogen interactions during CAM and will lead to the identification of new targets for intervention.

项目概要怀孕期间或产后不久的感染与大量发病率和全球死亡率。 B 族链球菌 (GBS) 是绒毛膜羊膜炎 (CAM) 和新生儿的主要原因败血症。胎盘充当 GBS 和宿主免疫反应之间的初始界面绒毛膜羊膜炎，构成宿主-病原体相互作用的场所。目前的理解由于缺乏揭示 CAM 的空间和时间成分的工具，CAM 的发病机制受到限制。胎盘感染。具体来说，我们缺乏对感染如何随着时间和跨区域传播的了解。胎盘结构。单细胞基因组学和空间转录组学的突破现在使对感染过程进行公正和系统的分析。在这里我们建议将这些方法应用于GBS 胎盘感染：检查宿主特异性反应、宿主-病原体界面和干扰 GBS 感染程序。在目标 1 中，我们将结合空间转录组学和单细胞 RNA-Seq 来研究 GBS 感染在新型上行感染和 CAM 小鼠模型中的进展。在目标 2 中，我们将同时研究原代人类感染期间宿主和病原体基因表达程序胎盘巨噬细胞。在目标 3 中，我们将通过系统评估来测试 GBS 感染的概念模型特定 GBS 基因的定向删除的效果。整合这些方法将提供丰富的视图 CAM 期间宿主与病原体的相互作用将导致新干预目标的确定。

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Enhanced Postnatal Acquisition of Hypervirulent Group B Streptococcus.

增强高毒力 B 族链球菌的产后获得。

DOI：
发表时间：
2019-10-30
期刊：
影响因子：
0
作者：
Ratner; Adam J
通讯作者：
Adam J

A periodic table of cell types.

细胞类型周期表。

DOI：
发表时间：
2019-06-27
期刊：
影响因子：
0
作者：
Xia, Bo;Yanai, Itai
通讯作者：
Yanai, Itai

Group B Streptococcus Capsular Serotype Alters Vaginal Colonization Fitness.

B 组链球菌荚膜血清型改变阴道定植适应性。

DOI：
发表时间：
2022
期刊：
影响因子：
0
作者：
Dammann, Allison N;Chamby, Anna B;Gonzalez, Francisco J;Sharp, Molly E;Flores, Karina;Shahi, Ifrah;Dongas, Sophia;Hooven, Thomas A;Ratner, Adam J
通讯作者：
Ratner, Adam J

Gardnerella and Prevotella: Co-conspirators in the Pathogenesis of Bacterial Vaginosis.

加德纳菌和普雷沃菌：细菌性阴道病发病机制的共谋者。

DOI：
发表时间：
2019
期刊：
影响因子：
0
作者：
Randis, Tara M;Ratner, Adam J
通讯作者：
Ratner, Adam J

The tempo and mode of gene regulatory programs during bacterial infection.

细菌感染期间基因调控程序的节奏和模式。

DOI：
发表时间：
2022-10-11
期刊：
影响因子：
8.8
作者：
Avital, Gal;Kuperwaser, Felicia;Pountain, Andrew W;Lacey, Keenan A;Zwack, Erin E;Podkowik, Magdalena;Shopsin, Bo;Torres, Victor J;Yanai, Itai
通讯作者：
Yanai, Itai