Biomarker discovery

One of the key aims of the new initiative will be to identify and characterize molecules or genetic markers that have the capacity to act as sentinels or predictors of the establishment of pathologies at an early stage. Unique identifiers for a key developmental stage, a diseased state, or exposure to an abiotic perturbation or contaminant will be identified, and will be essential for informed analysis of ontogenetic processes or environmental perturbations/insults to cells and the subsequent modelling of their dynamics.

Analysis

Systems-level analysis will be used to identify control pathways leading to specific cellular behaviours and responses to infection. Comparative mRNA-sew approaches, for instance, offer a rapid opportunity to identify transcriptionally regulated biomarkers in nonmodel organisms, and this technology is well developed on the Illumina sequencing platform. 

The analytical facility has developed a pipeline to undertake novel small molecule discovery based upon unbiased accurate mass metabolomics by liquid chromatography on time-of-flight instruments, followed by accurate mass quantitation by single reaction monitoring on triple quadrupole mass spectrometers.

Central to identifying biomarkers is the ability, developed in house, to align large replicated spectral datasets and identify significant differentially abundant molecules. These can then be integrated into multiple reaction monitoring methods to quantitatively assess several biomarkers simultaneously and structural identifications are undertaken in collaboration with other institutes.

Epidemiology

Epidemiology and public health research in PCMD is using large-scale transcriptional profile analysis and association genetics that identify and characterise common disease risks, and move epidemiology from unexplained statistical associations to measuring mechanism of effect at the molecular level. For example, associated signal linked to muscle repair and to advancing age are being identified in a current National Institutes of Health research project, while work on gene expression in obesity and diabetes is also underway, in collaboration with the Wellcome Case Control Consortium and a host of international institutions. In parallel, the effects of environmental xeno-estrogens are being analysed, with recent results linking a common xeno-estrogen to up-regulation of target receptor-encoding genes, at exposures that some have been claimed previously to be far too low to be bio-active.

This expertise in association genetics, genomics and biomarker identification will be harnessed in parallel with the development of novel photonic and electrochemical sensors for biomarker detection and physiological monitoring. For example Exeter’s Attogram label-free biomedical array imaging project applies Evanescent Wave Cavity Ring-down Spectroscopy to investigate molecules by direct absorption with detection levels of the order of 106 molecules.