Dr Jonathan R Swann

Background

In 2008 I obtained a PhD within the department of Biomolecular Medicine at Imperial College under the supervision of Professor Elaine Holmes. My thesis was titled 'Influence of gene-environment interaction on the gut microflora-mammalian contribution to metabolism and toxicity'. Here, a systems biology approach was applied to elucidate the influence of the gut microbiota on the mammalian biological system, with specific focus on how the microflora influence host metabolism and toxicity of xenobiotics. This systems biology approach incorpoarated both microarray-based transcriptomics and 1H NMR spectroscopy-based metabonomics. Funding for this PhD was provided by AstraZeneca and to make full use of this collaboration I spent several months working in the Molecular Toxicology laboratory that formed part of Global Safety Assessment. Whilst at AstraZeneca I received additional supervision from Professor Ian Wilson and Dr. James Sidaway. Here, I learned and applied a range of techniques including:

 

• Affymetrix-based transcriptomics
• Quantitative PCR
• Expression proteomics
• Protein analysis techniques, such as enzyme activity assays and Western blotting
• High performance liquid chromatography (HPLC)
• Liquid chromatography-mass spectrometry (LC-MS)

Current Research Interests

Current research is primarily involved in the application of metabonomics in large scale epidemiological studies. Specifically, to characterise metabolic profiles associated with psychosocial stress across a Taiwanese population using high resolution 1H NMR spectroscopy and UPLC-MS with multivariate statistical analysis and to relate these profiles to questionaire data on perceived stress level, medical history, anthropometric measurements and serological inflammatory measurements. This research is in collaboration with the Center for Population and Health, Georgetown University, and the Office of Population Research, Princeton University. Funding is provided by Georgetown University (NIH).

As an extention from research conducted during my PhD, work is continuing in the exploration of the gut microflora as a variable that modulates mammalian health. Maintaining a systems biology approach and incorporating UPLC-MS techniques with enhanced sensitivity, the impact of the gut microflora on host xenobiotic, lipid and energy metabolism is being studied. Additionally, as an alternative to the use of germ-free models, the impact of antibiotics on the gut microbiota is being characterised by systems biology tools. The aim is to develop experimental models for studying the gut microbiota that are more reflective of wild-type model.

Other research persuits include the application of 1H magic angle spinning (MAS) NMR spectroscopy to analyse intact tissue taken from liver biopsies collected pre- and post- transplantation. The aim of this research is to extract biomarkers that provide an assessment of doner liver quality prior to transplantation and to improve the prediction of the likelihood of primary graft dysfunction, after transplantation.