Dr James Mason

KCL Postal Address: Pharmaceutical Science Division
King's College, London
Franklin-Wilkins Building (5.22C)
150 Stamford Street
London, SE1 9NH
United Kingdom
 

Research Group – Pharmaceutical Biophysics
Teaching Department – Biochemistry

My research interests focus on the interaction of peptides or other drugs with biological membranes. Understanding these interactions at the molecular level allows us to modulate the activity of the peptide, leading to enhanced activity and reduced cellular toxicity. Membrane active peptides can have a variety of roles but we are particularly interested in peptides that have antibiotic properties or can be used as vectors for nucleic acids to deliver gene therapeutics to mammalian cells.
By studying natural and designed antibiotic peptides we aim to obtain rules for the rational design of antibiotics that are active against bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa, fungi and the malaria parasite Plasmodium falciparum.
Histidine rich amphipathic peptides can also be highly efficient gene or siRNA delivery vehicles. We have shown that such peptides are more efficient vectors when they can interact with negatively charged lipids in the target cell membrane. We aim to understand this interaction in more detail so that it can be exploited for biotechnological or therapeutic applications.
The research uses a wide range of biophysical methods in conjunction with in silico molecular dynamics simulations which provide data which we incorporate in an overall view, together with in vitro activity assays, transcript and metabolomic profiling of how both bacteria and host cells respond to being challenged by the peptides.
 
Specific research themes include:

• Application of solid-state NMR methodologies to peptide structure and membrane dynamics.
• Quantification of peptide secondary structure in membrane environments using Circular Dichroism (CD) and other optical spectroscopy methods.
• The role of conformational flexibility in the mechanism of action and toxicity of cationic alpha-helical amphipathic antimicrobials.
• The role of membrane interactions in the activity of human beta defensin-2 (hBD-2).
• Manipulating peptide-membrane interactions to enhance peptide mediated nucleic acid delivery and develop safe and efficient non-viral vectors.
• Linking the biophysical activities of antimicrobial peptides to a molecular genetic view of challenged bacteria and P. falciparum.
• Linking biophysical measurements to predictive in silico molecular dynamics simulations.
• Development of Magic Angle Spinning (MAS) NMR approaches to metabolomic profiling.

 
Collaborations are with Dr Ken Bruce, Dr Alex Drake, Dr Graham Mitchell, Dr Chris Lorenz (all from KCL), Dr Dominic Campopiano (University of Edinburgh), Dr Antoine Kichler (Généthon, Evry, France) and Dr Jenny Lam (Hong Kong University).