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Dr James Mason

Research interests

The goal of my research is to understand how the dynamic composition of biological membranes influences how organisms respond to their environments. In particular, we are interested in how they interact with molecules designed to disrupt, disorder and/or cross their membranes.
Our approach is to obtain a fundamental, molecular level understanding of the effect of peptides or other drugs on the structure, organisation and dynamics of model membranes designed to closely mimic the properties of key target membranes in nature. This information is then put into context by relating the observed behaviour of these compounds in living cells to their biophysical features.
In this way we are beginning to understand the role that biological membranes play in diverse areas including bacterial and malarial infections, genetic diseases and cancer metastasis.
Understanding the interactions of peptides with membranes 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 Pseudomonas aeruginosa, fungi and the malaria parasitePlasmodium 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 BruceDr Alex DrakeDr Sukhi Bansal, Dr Graham Mitchell, Dr Chris LorenzDr Victoria Sanz-MorenoProf Tony Ng (all from KCL), Dr Dominic Campopiano (University of Edinburgh), Dr Antoine Kichler (Généthon, Evry, France), Dr Jenny Lam (Hong Kong University) and Dr Michael McArthur (Procarta Biosystems Ltd.).

 

Dr Mason's research is/has been supported by the MRCBBSRCThe Wellcome Trustthe Hong Kong RFCIDApplied Photophysics Ltd and Procarta Biosystems Ltd.

Biographical details

James studied Biochemistry at St Peter's College, Oxford, undertaking his final year project with Professor Tony Watts. This was his first exposure to the tricky but fascinating world of biological membranes and led to his remaining in Oxford, at Keble College, for a further 4 years completing his D.Phil studies in the Department of Biochemistry under the supervision of Professor Watts.

 

In October 2001, James moved to Berlin to join Clemens Glaubitz at the FMP and then moved with Professor Glaubitz to Frankfurt, helping to set up the biological solid-state NMR group at the J. W. Goethe Universität which hosts a European Large Scale Facility for NMR.

 

Having completed this first post-doctoral post, James moved up the Rhine and crossed the border to Strasbourg, France. In the laboratory of Professor Burkhard Bechinger. James began his work on membrane active amphipathic peptides with collaborations with Antoine Kichler at Généthon, near Paris, and Marie-Hélène Metz Boutigue, Gilles Prévost and Ermanno Candolfi all in Strasbourg.

 

In 2007 James returned to the UK and took up a position as a Wellcome Trust VIP Fellow at King's College London where he continues to develop this research theme following his appointment as Lecturer in 2009.

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