Genetic differences between strains can give metabolic phenotype differences. These can be used to study both the effects of very specific differences (functional genomics), or else broad-brush effects from large numbers of differing genes (chemotaxonomy).
Burkholderia cepacia complex
These ubiquitous bacteria have a wide metabolic capacity, and so are often used in bioremediation projects. However they are also potential opportunistic human and plant pathogens. We want to ask two related questions - firstly, can we identify metabolic differences between these closely-related bacterial groups? And secondly, can these differences explain pathogenic potential?
Pichia is widely used as a "protein factory" to express recombinant proteins, but proteins can be misfolded if the rate of expression is too high. We aim to use metabolite profiling to identify molecular patterns that will be early warning markers of this incorrect folding.
Selected papers in microbial metabolomics (see ‘publications’ tab for full list):
- Bundy JG, Willey TL, Castell RS, Ellar D, Brindle KM. (2005) Discrimination of pathogenic clinical isolates and laboratory strains of Bacillus cereus by NMR-based metabolomic profiling. FEMS Microbiol. Lett. 242, 127-136.
- Bundy JG, Papp B, Harmston R, Browne RA, Clayson EM, Burton N, Reece RJ, Oliver SG, Brindle KM. (2007) Analysing metabolic networks using metabolic profiling in conjunction with flux coupling analysis. Genome Research 17, 510-519.
Surprisingly little is known about the metabolism of many invertebrates, even for major model organisms.
C. elegans is an important model organism, the first multicellular animal to have its whole genome sequenced. We are interested in how specific mutations affect the metabolic phenotypes, and whether these can be used to help understand gene function.
Lumbricus rubellus (the ''''red'''' earthworm)
Earthworms are key soil organisms, and as such, can be used to monitor soil contamination. I am interested in how metabolomics of earthworms can be used to assess environmental pollution - for instance, can we tell which compound(s) from a complex polluted site is actually having a biological effect?
Selected papers in invertebrate metabolomics (see ‘publications’ tab for full list):
- Bundy JG, Spurgeon DJ, Svendsen C, Hankard PK, Osborn D, Lindon JC, Nicholson JK. (2002) Earthworm species of the genus Eisenia can be phenotypically differentiated by metabolic profiling. FEBS Lett. 521, 115–120.
- Malmendal A, Overgaard J, Bundy JG, Sorensen JG, Nielsen NC, Loeschcke V, Holmstrup M. (2006) Metabolomic profiling of heat stress: hardening and recovery of homeostasis in Drosophila. Am. J. Physiol. 291, R205-212.
- Bundy JG, Keun H, Sidhu JK, Spurgeon DJ, Svendsen C, Kille P, Morgan AJ. (2007) Metabolic profile biomarkers of metal contamination in a sentinel terrestrial species are applicable across multiple sites. Environ. Sci. Technol. 41, 4458-4464.
BBSRC LOLA Award. Mapping Combinatorial Stress Responses in Bacteria Using Chimeric Proteins and Probabilistic Modelling, Imperial College London, 2009