Christopher M. Williams

On the future of “omics”: lipidomics

SummaryFollowing in the wake of the genomic and proteomic revolutions new fields of “omics” research are emerging. The metabolome provides the natural complement to the genome and proteome, however, the extreme physicochemical diversity of the metabolome leads to a subdivision of metabolites into compounds soluble in aqueous solutions or those soluble in organic solvents. A complete molecular and quantitative investigation of the latter when isolated from tissue, fluid or cells constitutes lipidomics. Like proteomics, lipidomics is a subject which is both technology driven and technology driving, with the primary technologies being mass spectrometry, with or without on-line chromatography and computer-assisted data analysis. In this paper we will examine the underlying fundamentals of different lipidomic experimental approaches including the “shotgun” and “top-down” global approaches, and the more targeted liquid chromatography – or gas chromatography – mass spectrometry approaches. Application of these approaches to the identification of in-born errors of metabolism will be discussed.

Osteological, biomolecular and geochemical examination of an early anglo-saxon case of lepromatous leprosy.

We have examined a 5th to 6th century inhumation from Great Chesterford, Essex, UK. The incomplete remains are those of a young male, aged around 21–35 years at death. The remains show osteological evidence of lepromatous leprosy (LL) and this was confirmed by lipid biomarker analysis and ancient DNA (aDNA) analysis, which provided evidence for both multi-copy and single copy loci from the Mycobacterium leprae genome. Genotyping showed the strain belonged to the 3I lineage, but the Great Chesterford isolate appeared to be ancestral to 3I strains found in later medieval cases in southern Britain and also continental Europe. While a number of contemporaneous cases exist, at present, this case of leprosy is the earliest radiocarbon dated case in Britain confirmed by both aDNA and lipid biomarkers. Importantly, Strontium and Oxygen isotope analysis suggest that the individual is likely to have originated from outside Britain. This potentially sheds light on the origins of the strain in Britain and its subsequent spread to other parts of the world, including the Americas where the 3I lineage of M. leprae is still found in some southern states of America.

Shotgun cholanomics of ileal fluid.

In this study we have developed a rapid method for the shotgun analysis of bile acids in intestinal fluid. The method is semi-quantitative, and requires little sample preparation. Bile salts might contribute to the pathogenesis of Crohn’s disease. In a pilot study we demonstrate the method by analysing the bile acid content of ileal fluid from seven Crohn’s disease patients and three healthy controls. The dominant bile acids observed were di and/or trihydroxycholanoates, di- and/or trihydroxycholanoylglycines, di- and/or tri-hydroxycholanoyltaurines, monosulphated dihydroxycholanoates and monosulphated dihydroxycholanoylglycine. The method can be similarly applied to samples derived from other parts of the intestine.

Morphological and biomolecular evidence for tuberculosis in 8th century AD skeletons from Bélmegyer-Csömöki domb, Hungary

Macromorphological analysis of skeletons, from 20 selected graves of the 8th century AD Bélmegyer-Csömöki domb, revealed 19 cases of possible skeletal tuberculosis. Biomolecular analyses provided general support for such diagnoses, including the individual without pathology, but the data did not show coherent consistency over the range of biomarkers examined. Amplification of ancient DNA fragments found evidence for the Mycobacterium tuberculosis complex DNA only in five graves. In contrast, varying degrees of lipid biomarker presence were recorded in all except two of the skeletons, though most lipid components appeared to be somewhat degraded. Mycobacterial mycolic acid biomarkers were absent in five cases, but the weak, possibly degraded profiles for the remainder were smaller and inconclusive for either tuberculosis or leprosy. The most positive lipid biomarker evidence for tuberculosis was provided by mycolipenic acid, with 13 clear cases, supported by five distinct possible cases. Combinations of mycocerosic acids were present in all but three graves, but in one case a tuberculosis-leprosy co-infection was indicated. In two specimens with pathology, no lipid biomarker evidence was recorded, but one of these specimens provided M. tuberculosis complex DNA fragments.

'That boundless ocean of mountains': British alpinists and the appeal of the Canadian Rockies, 1885-1920

Following the completion of the Canadian Pacific Railway in 1885, mountaineers began to explore the Rocky Mountains. Prominent British climbers included Green, Outram and Collie. Taking issue with Sandfords interpretation, the appeal of the Rockies for British Alpinists is examined. The Rockies were compared with the Alps, viewed as an Alpine playground, and represented as an authentic wilderness. Superficial manifestations of imperialism need contextualizing within a shared mountaineering ethos that nevertheless accommodated differences of emphasis. Close organizational links between the Alpine Club and the Alpine Club of Canada culminated in the affiliation of the latter to the former in 1920.