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Biology subjects

Mann, G. E.

Publications and source records attributed to Mann, G. E..

2 recordsLinked to original sources

Opto-lipidomics of tissues

Lipid metabolism and signalling play pivotal functions in biology and disease development. Despite this, there is currently no optical technique available that can directly visualise the lipidome in tissues. In this study, we introduce opto-lipidomics, a new approach to optical molecular tissue imaging. We expand the capability of vibrational Raman spectroscopy to identify individual lipids in complex tissue matrices through correlation with desorption electrospray ionisation (DESI) - mass spectrometry imaging in an integrated instrument. A computational pipeline of inter-modality regression analysis is established to extract lipidomic information from optical vibrational spectra. Opto-lipidomic imaging of transient cerebral ischemia-reperfusion injury in a murine model of ischemic stroke demonstrates the visualisation and identification of lipids in disease with unprecedented molecular specificity using light. Furthermore, we deploy opto-lipidomics in a handheld fiber-optic Raman probe and demonstrate real-time classification of bulk brain tissues based on specific lipid abundances. Opto-lipidomics opens a host of opportunities to study lipid biomarkers for diagnostics, prognostics, and novel therapeutic targets.

bioengineering↗

Human blood vessel organoids reveal a critical role for CTGF in maintaining microvascular integrity

The microvasculature plays a key role in tissue perfusion, transport of mediators, and exchange of gases and metabolites to and from tissues. Microvascular dysfunction has emerged as an important contributor to cardiovascular diseases. In this study we used human blood vessel organoids (BVOs) as a model of the microvasculature to delineate the mechanisms of microvascular dysfunction caused by metabolic rewiring. BVOs fully recapitulated key features of the normal human microvasculature, including reliance of mature endothelial cells (ECs) on glycolytic metabolism, as concluded from metabolic flux assays using 13C-glucose labelling and mass spectrometry-based metabolomics. Treatment of BVOs with PFK15, a pharmacological inhibitor of glycolysis, resulted in rapid tissue restructuring, vessel regression with reduced pericyte coverage and alterations in tight junction morphology. Proteomic analysis of the BVO secretome revealed remodelling of the extracellular matrix and differential expression of paracrine mediators such as CTGF. Treatment with recombinant CTGF recovered tight junction formation and increased pericyte coverage in microvessels. Our metabolic and proteomics findings demonstrate that BVOs rapidly undergo restructuring in response to metabolic changes and identify CTGF as a critical paracrine regulator of microvascular integrity.

cell biology↗