INSPIRE Track 1: Resolving and optogenetically perturbing biofilms at the single-cell level

INSPIRE奖的部分资金来自生物科学理事会分子与细胞生物科学部的系统与合成生物学项目、数学与物理科学理事会物理部的生命系统物理学，以及工程理事会化学、生物工程、环境和运输系统部的生物技术、生化和生物质工程项目。智力优势：在自然环境中，细菌主要存在于称为生物膜的多细胞表面结合群落中。虽然生物膜在废水处理中是理想的，但生物膜因引起慢性、医疗设备相关和医院相关感染以及对几乎所有材料表面的持续损害等不良问题而臭名昭著。生物膜中的细胞与自由生活的细胞表现出惊人的差异，例如产生粘合聚合物，对抗生素的耐受性增加1000倍。迄今为止的研究仅限于对生物膜形成的研究，当只有少数细胞存在时，或者对整个结构的总体表征。pi最近在显微镜学上取得了突破：他们在生物膜中分解了单个细胞。这是第一次有人“窥视”生物膜，观察它在模拟环境、医疗和工业系统的条件下，一个细胞一个细胞地发育。pi还开发了使用遗传、机械、化学和光学手段扰乱生物膜的程序。pi建议表征从基因到基因组和从细胞到集体的生物膜。该项目基于一种全新的方法，这种方法对于获得解决对科学、工程和社会具有广泛影响的基本问题所必需的理解至关重要。更广泛的影响：这是一个在物理，生物和工程界面的项目，因此，为学生和博士后研究人员提供了特殊的研究教育机会。此外，每位调查员在教学、推广和服务方面都有出色的记录。

This INSPIRE award is partially funded by the Systems and Synthetic Biology program in the Division of Molecular and Cellular Biosciences in the Directorate for Biological Sciences, the Physics of Living Systems in the Division of Physics in the Directorate for Mathematical & Physical Sciences, and the Biotechnology, Biochemical, and Biomass Engineering program in the Division of Chemical, Bioengineering, Environmental, and Transport Systems, in the Directorate for Engineering. INTELLECTUAL MERIT: In their natural environments, bacteria primarily exist in multicellular, surface-bound communities called biofilms. While biofilms are desirable in the context of wastewater treatment, biofilms are notorious for causing undesirable problems such as chronic, medical device-associated, and hospital-associated infections, and persistent damage to surfaces of nearly all materials. Cells in biofilms display striking differences from cells that are free living, such as production of adhesive polymers, and a 1,000-fold increase in tolerance to antibiotics. Studies to date have been limited to investigations of biofilm formation, when only a few cells are present, or to overall characterization of the entire structure. The PIs made a recent breakthrough in microscopy: they resolved the individual cells in biofilms. This is the first time anyone has peered "into" a biofilm, to watch it develop, cell by cell, under conditions that model environmental, medical, and industrial systems. The PIs have also developed procedures to perturb the biofilm using genetic, mechanical, chemical and optical means. The PIs propose to characterize biofilms from the gene to the genome and from the cell to the collective. The project is based on a radically new approach that is essential to gain the understanding necessary to solve a fundamental problem with broad implications for science, engineering, and society. BROADER IMPACTS: This is a project at the interface of Physics, Biology and Engineering, and as such, offers to the students and postdoctoral researchers involved exceptional research educational opportunities. Moreover, each investigator has remarkable track records in teaching, outreach, and service.