Mechanisms of membrane biogenesis and peptidoglycan remodeling during sporulation

孢子形成过程中膜生物发生和肽聚糖重塑的机制

• 批准号: RGPIN-2015-04345
• 负责人: Tocheva, Elitza
• 金额: $ 3.14万
• 依托单位: University of British Columbia
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=688738
• 关键词: Mechanisms; membrane; biogenesis; peptidoglycan; remodeling

My research program seeks to understand the structural and functional changes that occur in the bacterial cell envelope during growth and cell division. Although bacteria occupy every niche in the biosphere and sustain life on this planet, they are faced with unpredictable environments. To survive, they have evolved a sophisticated, multilayered cell envelope structure composed of either one or two membranes and a mesh-like polymer (peptidoglycan) that protects them while allowing the selective passage of nutrients and waste products. Spatial and temporal regulation of changes in the cell envelope is essential to bacterial growth and division. Moreover, the bacterial cell envelope is a major target for antimicrobials. Thus, research into the bacterial cell envelope provides insight into fundamental biological processes and is critical for understanding human health and disease.******Some bacteria have evolved mechanisms to protect their DNA from harsh environmental conditions by forming spores. These spores can remain viable for years without water or nutrients and can resist UV irradiation, heat, pH extremes and oxidative damage. Spore formation involves complex morphological changes in the membranes and peptidoglycan of single- and double-membraned bacteria and thus is ideal for studies of the bacterial cell envelope. *******In addition to being a useful model system, spore formation has significant implications for human health and disease. Examples of sporulating pathogenic bacteria include Bacillus cereus, which causes foodborne illness, Clostridium botulinum and C. tetani, the causative agents of botulism and tetanus, respectively, and Bacillus anthracis, which has been linked to bio-terrorism. Sporulating bacteria have been used for the production of antibiotics and enzymes, the delivery of vaccines and therapeutic agents, and the design of whole-cell biosensors. Interfering with the formation of a mature spore can help further develop better antimicrobial agents.*******By applying a range of approaches drawn from bioinformatics, molecular genetics, cell biology and structural biology with main emphasis on cryo electron tomography and super-resolution fluorescence light microscopy, I will characterize the structural and functional changes of the bacterial cell envelope during sporulation. Over the next five years, my research program will focus on characterizing two aspects of sporulation: 1) biogenesis of the outer membrane in double-membraned bacteria and 2) peptidoglycan remodeling in single- and double-membraned bacteria.**

我的研究计划旨在了解在生长和细胞分裂过程中细菌细胞包膜中发生的结构和功能变化。虽然细菌占据了生物圈中的每一个生态位，并在这个星球上维持生命，但它们面临着不可预测的环境。为了生存，它们进化出一种复杂的多层细胞包膜结构，由一层或两层膜和一种网状聚合物（肽聚糖）组成，这种聚合物保护它们，同时允许营养物质和废物选择性通过。细胞被膜变化的时空调控对细菌的生长和分裂至关重要。此外，细菌细胞包膜是抗微生物剂的主要靶标。因此，对细菌细胞包膜的研究提供了对基本生物过程的深入了解，对于了解人类健康和疾病至关重要。一些细菌已经进化出了通过形成孢子来保护其DNA免受恶劣环境条件影响的机制。这些孢子可以在没有水或营养的情况下存活数年，并且可以抵抗紫外线照射，热，pH极端和氧化损伤。孢子形成涉及单膜和双膜细菌的膜和肽聚糖的复杂形态变化，因此是研究细菌细胞被膜的理想方法。** 除了作为一个有用的模型系统，孢子形成对人类健康和疾病有重要意义。孢子形成致病菌的实例包括引起食源性疾病的蜡状芽孢杆菌、肉毒梭菌和C.肉毒杆菌和破伤风的病原体，以及与生物恐怖主义有关的炭疽杆菌。产孢细菌已被用于生产抗生素和酶，疫苗和治疗剂的输送，以及全细胞生物传感器的设计。干扰成熟孢子的形成可以帮助进一步开发更好的抗菌剂。通过应用一系列的方法，从生物信息学，分子遗传学，细胞生物学和结构生物学，主要侧重于冷冻电子断层扫描和超分辨率荧光显微镜，我将表征芽孢形成过程中细菌细胞包膜的结构和功能变化。在接下来的五年里，我的研究计划将集中在表征孢子形成的两个方面：1）双膜细菌外膜的生物发生和2）单膜和双膜细菌中的肽聚糖重塑。