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Details of Grant 

EPSRC Reference: EP/H02994X/1
Title: Understanding Peptide Antibiotics at the Single Molecule Level
Principal Investigator: Cronin, Dr B
Other Investigators:
Researcher Co-Investigators:
Project Partners:
University of Ljubljana
Department: Oxford Chemistry
Organisation: University of Oxford
Scheme: Postdoc Research Fellowship
Starts: 01 April 2010 Ends: 08 September 2012 Value (£): 294,165
EPSRC Research Topic Classifications:
Analytical Science Chemical Biology
EPSRC Industrial Sector Classifications:
Pharmaceuticals and Biotechnology
Related Grants:
Panel History:
Panel DatePanel NameOutcome
27 Jan 2010 PDRF CDIP Interview Panel Announced
17 Dec 2009 PDRF CDIP Sift Panel Excluded
Summary on Grant Application Form
Antimicrobial peptides are agents of the most ancient defence systems; they assist multicellular organisms in fighting against microbes. Most membrane active peptides act by affecting lipid bilayer integrity either by disruption or pore formation. Our knowledge of the pores formed by antimicrobial peptides is limited as their small size and heterogeneity makes them difficult to study using many conventional techniques. Recent advances in methods to detect individual molecules give us the opportunity to explore the mechanism of action of these peptides in greater detail. I propose to study the mechanism of action of several membrane active peptides found in nature which bind to and insert into lipid bilayers to form pores. I will study three groups of pore forming compounds by applying simultaneous single molecule fluorescence and single channel electrical recording measurements to image the pores they form.1. Alamethicin and magainin II; the two archetypal pore forming peptides.2. Equinatoxin II; an actinoporin, part of the host defence mechanism of the sea anemone Actinia equine.3. Daptomycin; a lipopeptide antibiotic in clinical use.At a time of increasing bacterial resistance these peptides are of great interest as potential antimicrobial drugs. Knowledge of their mechanism of defence against infection will also aid in the development of novel, synthetic antimicrobial agents. These compounds may augment immunity, restore potency or amplify the mechanisms of conventional antibiotics and minimise antimicrobial resistance mechanisms among pathogens.
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Organisation Website: http://www.ox.ac.uk