The BAM in bugs - understanding bacteria using a chemical biology toolbox. (SEARCEY_U17DTP)

抗菌素耐药性仍然是一个可怕的前景。有人提出，如果我们找不到新的杀灭细菌的方法，我们将回到常规手术可能被证明是致命的日子。我们需要了解细菌是如何发挥作用的。这项研究项目是一种令人兴奋的方法，利用合成化学、结构生物学和微生物学相结合的方法来研究革兰氏阴性细菌的基础生物学。这些细菌必须在它们的表面展示蛋白质(称为外膜蛋白质)，为此，它们使用了一种被称为BAM复合体的分子机器。UEA的董强江教授的研究引领了世界通过使用结晶学来理解BAM络合物的研究。在Mark Searcey教授的合作下，我们现在将设计和合成多肽和小分子，使我们能够操纵这种复合体，并了解它如何发挥作用，以及它如何可能成为设计新的抗菌剂的目标。该项目将需要在合成有机化学、多肽和小分子合成方面的技能，以及对发展结晶学和微生物学技能的兴趣。

Antimicrobial resistance remains a frightening prospect. It has been suggested that, should we fail to find new ways to kill bacteria, we will return to the days when a routine operation could prove fatal. We need to understand how bacteria function. This research project is an exciting approach to the study of the fundamental biology of Gram negative bacteria using a combination of synthetic chemistry, structural biology and microbiology. These bacteria have to display proteins (called outer membrane proteins) on their surface and to do this they use a molecular machine known as the BAM complex. Research from Professor Chiangjang Dong at UEA has led the world in understanding the BAM complex through the use of crystallography. In collaboration with Professor Mark Searcey, we will now design and synthesise peptides and small molecules that will allow us to manipulate this complex and to understand how it functions and how it could potentially become a target for the design of new antimicrobial agents. The project will require skills in synthetic organic chemistry, peptide and small molecule synthesis and an interest in developing skills in crystallography and microbiology.