Developing new analytical techniques and methods

Biochemical research is often limited by technical capabilities and sometimes by the lack of a clear analytical tool for a research problem. Our focus is on bridging these gaps by extending analytical capabilities into new areas of application and further refining techniques and methods. This process often involves adapting existing technologies for new applications (e.g. preparative high-performance liquid chromatography (HPLC) for compound-specific radiocarbon dating (McCullagh et al., Radiocarbon, 2010) or coupling ion-exchange chromatography   mass spectrometry analyse highly polar and ionic metabolomes (Walsby-Tickle et al., Comms. Biol., 2020).

 

Developing ion-exchange chromatography high-resolution mass spectrometry (IC-MS) for metabolomics applications

Central carbon metabolism drives critical cellular processes, including energy transduction, redox balance and the generation of molecular building blocks. However, these processes can be disrupted in a wide range of diseases, including diabetes, heart disease, microbial infections and cancer. Metabolomics is uniquely placed to explore these altered metabolic states but has a number of major technical challenges including providing comprehensive and reliable quantitative coverage of highly polar and ionic metabolites which make up the majority of the metabolites in primary metabolic pathways.

We have been advancing IC-MS techniques for both targeted and untargeted metabolomics applications. Our focus is the comprehensive analysis of highly polar and ionic metabolites from cells, tissues, and bio-fluid extracts to provide deeper insights into the metabolic alterations associated with disease states (Walsby-Tickle et al., Comms. Biol., 2020).

Compound-specific radiocarbon dating

The McCullagh Group has a track record of developing new techniques and applying existing techniques in novel areas. Notably, our early efforts in compound-specific radiocarbon dating and isotope analysis have led to the establishment of a method for radiocarbon dating individual amino acids, now employed worldwide. Among its applications is the gold standard for radiocarbon dating of archaeological bones using hydroxyproline. This breakthrough has resulted in a series of publications, including the earliest migrations of anatomically modern humans into Europe. (Marom et al., PNAS, 2012)

Stable isotopes analysis of proteinogenic amino acids

In parallel work to the development of compound-specific radiocarbon dating we developed an analytical mixed-mode chromatography method capable of separating the majority of proteinogenic amino acids using non-organic solvent mobile phases. This enabled interface with isotope ratio mass spectrometry which in turn provided the first non GC-C-MS based approach to underivatised compound-specific analysis of amino acids. This led to a series of studies into biochemical origins including plant proteins, and dietary studies in fish and human palaeodietary reconstruction (McCullagh et al., 2006).

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Selected publications
pnas 1116328109b page
vaccines
isotope ratio mass spectrometry paleodietary implications from intra individual comparisons page
walsby tickle et al