Systematic functional characterization of new bacterial cell envelope assembly factors

细菌是由复杂的细胞被膜包围的单细胞生物。这种包膜对于细菌的生长和存活是必不可少的，因为它界定了细胞并保护其免受环境攻击和渗透压变化的影响。我们许多最成功的抗生素，包括青霉素和万古霉素，靶细胞包膜组装。具有讽刺意味的是，我们对细菌细胞包膜的大部分了解都来自于使用这些抗生素作为功能探针。这无疑使我们对这些复杂和多样的结构的看法产生偏见和局限，表明需要采取其他办法。实际上，关于包膜组装是如何调节的以及不同层的合成是如何协调的，我们知之甚少。** 我设计了一种新的遗传筛选，使我们超越了以前以胚胎为中心的研究，并提高了我们对包膜组装过程的理解。使用这种创新的方法，我发现了许多细菌因素，这些因素似乎对包膜的生物发生至关重要。在我的新实验室里，我的目标是阐明这些新发现的因子的分子和生理功能。为此，我将结合联合收割机最先进的生物信息学，遗传学和生物化学方法以及分子和细胞生物学技术。发现新的包膜生物发生因子并了解它们的作用将使人们更广泛地理解细菌细胞如何调节和协调不同包膜层的合成。细菌是研究生命科学的优秀模型系统，该研究计划的结果将对细菌生理学，细胞生物学，基因组学，蛋白质组学，生物化学和分子微生物学领域产生重大影响。这项研究计划还将允许识别新的细菌脆弱性，以开发抗菌剂。**

Bacteria are unicellular organisms surrounded by a complex cell envelope. This envelope is essential for bacterial growth and survival as it delimits the cell and protects it against environmental assaults and changes in osmotic pressure. Many of our most successful antibiotics, including penicillin and vancomycin, target cell envelope assembly. Ironically, most of our knowledge about bacterial cell envelopes has come from using these antibiotics as functional probes. This has no doubt biased and limited our view of these complex and diverse structures, suggesting a need for alternative approaches. Actually very little is known about how envelope assembly is regulated and how the synthesis of the different layers is coordinated. **I have designed a new genetic screen to take us beyond previous antibiotic-centric studies and improve our understanding of the envelope assembly process. Using this innovative approach, I have discovered many bacterial factors that appear to be critical for biogenesis of the envelope. In my new lab, I aim at shedding light on the molecular and physiological functions of these newly identified factors. To do so, I will combine state-of-the-art bioinformatic, genetic and biochemical approaches as well as molecular and cellular biology techniques. Discovering new envelope biogenesis factors and understanding their role will allow a broader comprehension of how bacterial cells regulate and coordinate the synthesis of the different envelope layers. Bacteria are excellent model systems to study life sciences and the outcome of this research program should have a significant impact on the fields of bacterial physiology, cellular biology, genomics, proteomics, biochemistry and molecular microbiology. This research program will also permit the identification of new bacterial vulnerabilities for the development of antibacterial agents. **