We work at the interface between Biology, Chemistry and Mathematics, and most of projects have a metabolomics or proteomics flavour to them.
Mass spectrometry for high-throughput metabolomics
The MS-based gold standard for metabolomics is GC-MS. However this is slow
and laborious since it requires chemical derivatisation
and complicated deconvolution. By contrast, we have
been developing direct infusion ESI-MS (electrospray
ionisation) via flow injection for metabolic profiling; but, in the general
case, ion-suppression effects limit the utility of this approach. We are
therefore now concentrating on developing direct laser desorption ionisation-MS
that requires no matrix, and which would thus allow the very high throughput
analysis of cell extracts spotted onto appropriate plates and analysed in a
standard MALDI-MS instrument.
Integrative ’omic analyses for understanding
biological systems
Improving the stability of whole cell biocatalysts would allow a much wider
range of redox enzymes to be exploited to manufacture
speciality chemicals and pharmaceuticals. However, this is an extremely complex
task, since a large number of genes (many unidentified) interact to determine
biocatalyst performance in the presence of toxic process materials. We are
using a systems biology approach to identify and rank the importance of the
genes determining biocatalyst stability.
Development of a wide variety of Raman spectroscopic methods
Raman spectroscopy is a method that measures the inelastic light scattered from
a monochromatic light source. It is attracting great interest with biology
because it is non-destructive and gives chemical information about the sample
under investigation. However, the ‘normal’ Raman effect
is very weak, since typically only 1 in every 108 photons exchange
energy with a molecular bond vibration, the rest of the photons being Rayleigh
scattered. Consequently data acquisition for spectra from biological samples
with a suitably high signal-to-noise ratio still often takes 5-15 min. Thus we
are concentrating on enhancing the Raman signal via surface enhanced Raman
spectroscopy (SERS) and deep UV resonance Raman spectroscopy (UVRR).
Metabolomics and proteomics in health and disease
Metabolite and protein profiling are emerging as very powerful methods to
study disease processes and we are investigating the potential of these methods
both temporally and spatially. Projects include:
(a) Monitoring the fate of pharmaceuticals in marine and freshwater
environments by assessing the impact of pharmaceutical exposure on the metabolome of ecologically important groups of microbes in
terms of the biochemical pathways by which drugs undergo degradation and the
biodiversity of microbial communities.
(b) Investigating various methods that produce chemical maps that can be used
for imaging for chemical pathology. These methods include mass
spectrometry for proteomics, whilst for metabolomics FT-IR and Raman spectroscopies are being developed.
(c) Finally, we are also investigating MALDI-MS and UVRR spectroscopy for
predicting human diseases from serum and for biomarkers discovery.
Rapid characterisation of microorganisms
In view of the increasing prevalence of microbial infections and the expanding
ability of such organisms to acquire (multiple) resistance(s) to antimicrobial
agents, there is a continuing need for the rapid characterisation and
speciation of bacteria and fungi. We are developing a wide variety of
analytical instrumentation-based approaches often referred to as
‘whole-organism fingerprinting’ for the rapid identification of bacteria and
fungi. We are particularly interested in methods based on ESI-MS and MALDI-MS,
Fourier transform infrared (FT-IR) spectroscopy and Raman spectroscopy.
This is a general theme that we have been working on for the last 15 years and
touches on all of the above.
Rapid characterisation of foodstuffs
Foods (either muscle food (e.g., meat, poultry and seafood), vegetables, or
refined products (e.g., fruit juices)) are described as spoiled if organoleptic changes make them unacceptable to the
consumer. Spoilage is generally a result of decomposition and the formation of
metabolites resulting from the growth of micro-organisms. It is important to
both the retailer and consumer that any spoiled food be
removed from sale and the contaminating organism be identified as either a
pathogen or a 'harmless' saprophyte. We have been investigating FT-IR
spectroscopy for the quantitative analysis of food spoilage
In addition, there is a continuing requirement for rapid, accurate, automated
methods for determining whether a particular foodstuff has the provenance
claimed for it or whether it has been adulterated with or substituted by a
lower-grade material. This is also an area where analytical biotechnology can
play a part and over the years we have been investigating the adulteration and
origin of a wide variety of foods including olive oil, orange juice, cocoa
butter and honey.
This is a general theme that we have been working on for the last 10 years and
touches on all of the above.
Last updated 02 February 2005