Mechanisms of membrane biogenesis and peptidoglycan remodeling during sporulation

我的研究项目旨在了解细菌细胞膜在生长和细胞分裂过程中发生的结构和功能变化。尽管细菌占据了生物圈中的每一个利基，并维持着地球上的生命，但它们面临着不可预测的环境。为了生存，它们进化出了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，这种聚合物在保护它们的同时允许营养物质和废物的选择性通过。细胞膜变化的空间和时间调节对细菌的生长和分裂至关重要。此外，细菌细胞膜是抗菌剂的主要靶标。因此，对细菌细胞膜的研究提供了对基本生物过程的洞察，对于了解人类健康和疾病至关重要。一些细菌已经进化出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，并能抵抗紫外线照射、高温、极端pH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膜的理想方法。孢子形成除了是一种有用的模式系统外，还对人类健康和疾病有重大影响。产孢子型病原菌的例子包括导致食源性疾病的蜡状芽孢杆菌、肉毒杆菌中毒和破伤风的病原体肉毒梭菌和破伤风杆菌，以及与生物恐怖主义有关的炭疽芽孢杆菌。产孢子菌已被用于生产抗生素和酶、运送疫苗和治疗剂以及设计全细胞生物传感器。干扰成熟孢子的形成有助于进一步开发更好的抗菌剂。*通过应用生物信息学、分子遗传学、细胞生物学和结构生物学的一系列方法，主要是低温电子断层扫描和超分辨荧光显微镜，我将表征细菌细胞膜在孢子形成过程中的结构和功能变化。在接下来的五年里，我的研究计划将专注于表征孢子形成的两个方面：1)双膜细菌外膜的生物发生；2)单膜和双膜细菌的肽聚糖重塑。**

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.**