Understanding antimicrobial peptide mechanisms; a rationale for the improved design of antibiotics and vectors

拟议的研究中心是了解天然和合成肽如何与生物膜相互作用，作为其作用机制的一部分。了解这一过程可能对开发新的抗生素、对抗MRSA和艰难梭菌等细菌或恶性疟原虫（导致疟疾）等寄生虫，以及治疗囊性纤维化等遗传性疾病的基因治疗载体至关重要。生物膜包围着人类和细菌细胞，构成了细胞与其环境之间的选择性屏障，因此它们的特性以及必须穿过这些膜或与这些膜相互作用的化合物的特性对于寻求开发新型抗生素或复杂新疗法的研究人员来说非常有趣。多肽样品将通过化学合成技术或利用细菌的机制来制备。结合生物物理技术，特别是固态核磁共振波谱，一种强大的方法来确定肽和膜的结构和动态特征，他们相互作用，光学光谱学将被用来准确地了解肽在膜环境中的行为。当我们了解天然存在的肽的哪些特征对其功能很重要以及如何操纵它们时，这些信息将用于设计可能具有更有效的抗生素活性或基因传递功能的肽。

The proposed research centres on understanding how natural and synthetic peptides interact with biological membranes as part of their mechanism of action. Understanding this process may be crucial to the development of new antibiotics, to fight bacteria such as MRSA and C. difficile or parasites such as Plasmodium falciparum (which causes malaria), and gene therapeutic vehicles to treat genetic diseases such as cystic fibrosis. Biological membranes surround human and bacterial cells and comprise a selective barrier between the cell and its environment and hence their properties and those of compounds that must cross or interact with these membranes are extremely interesting to researchers who seek to develop new classes of antibiotic or sophisticated new therapies. Peptide samples will be prepared either by using chemical synthesis techniques or by harnessing the machinery of bacteria. A combination of biophysical techniques in particular solid-state NMR spectroscopy, a powerful method for determining structural and dynamic features of both the peptides and the membrane that they interact with, and optical spectroscopy will be employed to understand exactly how the peptides behave in the membrane environment. When we understand what features of naturally occurring peptides are important to their function and how they can be manipulated, this information will be used to design peptides that may have more effective antibiotic activity or gene delivery function.