Dr Pat Langridge-Smith

Reader in Chemical Physics

Research summary

The research activities of my group, the EMSG, are very broadly based and their undergraduate training ranges across traditional disciplines such as molecular genetics, biology, geology and geophysics, electrical engineering through to chemical physics. A unifying theme, however, is the use of the most advanced mass spectrometric and laser instrumentation together with miniaturised techniques for sample handling and microseparation to address important areas of measurement science.

For the past five years the group has been heavily involved with the RC-UK funded Interdisciplinary Research Collaboration (IRColl) in Proteomic technologies - RASOR - a unique research programme to advance proteomics and its application in life sciences and biomedical research. The RASOR research programme is underpinned by the Doctoral Training Centre in Proteomic and Cell Technologies which trains an average of 10 students per year on a 4 year MRes/PhD programme in scientific areas interleaving with RASOR objectives, in the fields of proteomics, imaging and microfluidics, with a particular focus on a wide range of technologies in cell and molecular biology, microarrays, sensors, instrumentation and spectroscopy.

Within the EMSG training is also given, as appropriate, in a variety of techniques for experimental measurement science, including advanced mass spectrometry, microseparation science, picosampling techniques and laser instrumentation. Any project can be tailored to suit the interests of the individual concerned. However, an interdisciplinary attitude to scientific problem solving is essential. For further information consult the group web site or drop in and talk to one of us.

Other research opportunities are also available within SIRCAMS - the Scottish Instrumentation and Resource Centre for Advanced Mass Spectrometry, which I established in 2002. SIRCAMS is one of Europe's best equipped multi-user facilities for high field Fourier transform ion cyclotron resonance mass spectrometry. FT-ICR MS is the technique of choice for many biological problems due to its ultra-high resolution, mass measurement accuracy and high sensitivity, which in favorable cases can enable experiments to be carried out on samples containing as little as 100 molecules.

We have three Bruker Daltonics FT-ICR MS instruments, equipped with a wide range of ionization sources. One of our main interests is structural determination of proteins, RNA, DNA, and protein complexes using top-down fragmentation techniques. With FT-ICR MS specific ions can be isolated and trapped, permitting further experimentation such as fragmentation studies using IR lasers or electron capture dissociation (ECD). ECD is of particular importance due to the nonergodic breakdown mechanism, thus enabling the study of post-translational modifications in proteins.

  1. Top-Down Protein Sequencing by CID and ECD using Desorption Electrospray Ionisation (DESI) and High-Field FT-ICR Mass Spectrometry, Stokes AA, Clarke DJ, Weidt S, Langridge-Smith P, Mackay CL. Int. J. Mass. Spectrom., 2010, 289, 54
  2. Online Quench-Flow Electrospray Ionization Fourier Transform Ion Cyclotron Resonance Mass Spectrometry for Elucidating Kinetic and Chemical Enzymatic Reaction Mechanisms, Clarke DJ, Stokes AA, Langridge-Smith P, Mackay CL. Anal. Chem., 2010, 82, 1897
  3. Subdivision of the Bacterioferritin Comigratory Protein Family of Bacterial Peroxiredoxins Based on Catalytic Activity, Clarke DJ, Ortega XP, Mackay CL, Valvano MA, Govan JRW, Campopiano DJ, Langridge-Smith P, Brown AR. Biochem., 2010, 49, 1319