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

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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.