权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Supplement for Purchase of a Cell Sorter for R35GM133797

购买 R35GM133797 细胞分选仪的补充

基本信息

批准号：
10795368
负责人：
Fuzhong Zhang
金额：
$ 24.93万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-01 至 2024-06-30
项目状态：
已结题

项目摘要

PROJECT SUMMARY Cellular heterogeneity is ubiquitous across all domains of life. Genetically identical cells can display heterogeneous metabolic activities, even when grown in identical environments. In bacteria, metabolic heterogeneity can shape the ensemble growth rate and affect antibiotic tolerance. In bacteria, metabolic heterogeneity shapes the ensemble growth rate and affects antibiotic tolerance. However, many questions remain regarding metabolic heterogeneity. For instance, what determines the size of metabolic fluctuation? How is metabolic heterogeneity regulated? Can we control metabolic heterogeneity and therefore eliminate drug-tolerant cells? The lack of fundamental understanding has severely limited the development of effective treatments for multiple diseases in which a small number of transiently tolerant cells often cause disease recurrence. The current MIRA project aims to obtain a systematic understanding of bacteria metabolic heterogeneity by using single-cell metabolic analysis methods. Using an engineered metabolic pathway that produces a unique fluorescent metabolite―betaxanthine, this project aims to determine the origin, dynamics, and propagation of metabolic heterogeneity. Furthermore, this project studies how transcriptional regulations affect metabolic heterogeneity, and explores the influence of metabolic heterogeneity on drug tolerance and strategies to reduce metabolic heterogeneity. This Equipment Supplement application requests fund to purchase a new flow cytometer to replace an old flow cytometer in the PI’s lab that was broken and is not repairable. Flow cytometer is essential to the parental project in studying metabolite heterogeneity. Obtaining a new flow cytometer will substantially accelerate the productivity of this project and enable new capabilities to the PI’s research group to explore new areas in metabolite heterogeneity.

项目概要细胞异质性在生命的各个领域中普遍存在。基因相同的细胞可以即使在相同的环境中生长，也表现出异质的代谢活动。在对于细菌来说，代谢异质性可以塑造整体生长速度并影响抗生素宽容。在细菌中，代谢异质性决定了整体生长速度并影响抗生素耐受性。然而，关于代谢异质性仍然存在许多问题。为了比如代谢波动的大小由什么决定？代谢异质性如何监管？我们能否控制代谢异质性从而消除耐药细胞？缺乏基本认识严重限制了有效的发展治疗多种疾病，其中少数短暂耐受的细胞经常引起疾病复发。目前的 MIRA 项目旨在系统地了解利用单细胞代谢分析方法研究细菌代谢异质性。使用工程代谢途径产生独特的荧光代谢物——倍他黄素，这种该项目旨在确定代谢异质性的起源、动态和传播。此外，该项目研究转录调控如何影响代谢异质性，探讨代谢异质性对耐药性的影响及降低策略代谢异质性。该设备补充申请要求资金购买新的流式细胞仪更换 PI 实验室中损坏且无法修复的旧流式细胞仪。流式细胞仪对于研究代谢物异质性的亲代项目至关重要。获得新的流量细胞仪将大大提高该项目的生产力并实现新功能向 PI 的研究小组提供帮助，探索代谢物异质性的新领域。