Michael Wakelam

Michael Wakelam 1955 - 2020: read the Institute's announcement on hearing about the death of Michael on 31st March.

Research Summary

We aim to understand the essential physiological functions of lipids. Lipids are highly dynamic structures with structural, metabolic and signalling roles. To fully understand the roles that lipids have in cell function during ageing we need the ability to determine their individual changes.

The cellular lipidome is extremely complex, with distinct classes of lipids each containing many molecular species that can differ both in the length of each acyl chain present and in the number and position of double bonds.

In our lab we have pioneered the use of high-sensitivity liquid chromatography-mass spectrometry (LC-MS) technology to rapidly and comprehensively measure the levels of lipids in a wide range of cell types, tissues and tumours. The lipidome of a cell typically comprises of ~ 1500 distinct lipid species measurable with current LC-MS technology. However, this number is most likely an underestimate since there are theoretically closer to 10 000 distinct lipid species in the lipidome.

The principal aim of our laboratory is to better understand how the distinct lipid species of a cell’s lipidome function during the healthy ageing of the whole animal.

​To achieve this we use a multidisciplinary approach combining LC-MS analysis, protein biochemistry, cell biology and genetic manipulation of model organisms. This allows us to identify the cellular signalling pathways and processes that individual lipid species regulate, and to investigate how the enzymes that determine the composition of the lipidome are regulated in response to changes in the environment.

Latest Publications

Potential Role of Oral Rinses Targeting the Viral Lipid Envelope in SARS-CoV-2 Infection.
O'Donnell VB, Thomas D, Stanton R, Maillard JY, Murphy RC, Jones SA, Humphreys I, Wakelam MJO, Fegan C, Wise MP, Bosch A, Sattar SA

Emerging studies increasingly demonstrate the importance of the throat and salivary glands as sites of virus replication and transmission in early COVID-19 disease. SARS-CoV-2 is an enveloped virus, characterized by an outer lipid membrane derived from the host cell from which it buds. While it is highly sensitive to agents that disrupt lipid biomembranes, there has been no discussion about the potential role of oral rinsing in preventing transmission. Here, we review known mechanisms of viral lipid membrane disruption by widely available dental mouthwash components that include ethanol, chlorhexidine, cetylpyridinium chloride, hydrogen peroxide, and povidone-iodine. We also assess existing formulations for their potential ability to disrupt the SARS-CoV-2 lipid envelope, based on their concentrations of these agents, and conclude that several deserve clinical evaluation. We highlight that already published research on other enveloped viruses, including coronaviruses, directly supports the idea that oral rinsing should be considered as a potential way to reduce transmission of SARS-CoV-2. Research to test this could include evaluating existing or specifically tailored new formulations in well-designed viral inactivation assays, then in clinical trials. Population-based interventions could be undertaken with available mouthwashes, with active monitoring of outcome to determine efficacy. This is an under-researched area of major clinical need.

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Function (Oxford, England), 1, 1, 2020

PMID: 33215159

Steps Towards Minimal Reporting Standards for Lipidomics Mass Spectrometry in Biomedical Research Publications.
O'Donnell VB, FitzGerald GA, Murphy RC, Liebisch G, Dennis EA, Quehenberger O, Subramaniam S, Wakelam MJO

None listed

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Circulation. Genomic and precision medicine, 1, 1, 16 Nov 2020

PMID: 33196315

Update on LIPID MAPS Classification, Nomenclature and Shorthand Notation for MS-derived Lipid Structures.
Liebisch G, Fahy E, Aoki J, Dennis EA, Durand T, Ejsing C, Fedorova M, Feussner I, Griffiths WJ, Koefeler H, Merrill AH, Murphy RC, O'Donnell VB, Oskolkova OV, Subramaniam S, Wakelam M, Spener F

A comprehensive and standardized system to report lipid structures analyzed by mass spectrometry is essential for the communication and storage of lipidomics data. Herein, an update on both the LIPID MAPS classification system and shorthand notation of lipid structures is presented for lipid categories Fatty Acyls (FA), Glycerolipids (GL), Glycerophospholipids (GP), Sphingolipids (SP), and Sterols (ST). With its major changes, i.e. annotation of ring double bond equivalents and number of oxygens, the updated shorthand notation facilitates reporting of newly delineated oxygenated lipid species as well. For standardized reporting in lipidomics, the hierarchical architecture of shorthand notation reflects the diverse structural resolution powers provided by mass spectrometric assays. Moreover, shorthand notation is expanded beyond mammalian phyla to lipids from plant and yeast phyla. Finally, annotation of atoms is included for the use of stable isotope-labelled compounds in metabolic labelling experiments or as internal standards.This update on lipid classification, nomenclature and shorthand annotation for lipid mass spectra is considered a standard for lipid data presentation.

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Journal of lipid research, 1, 1, 09 Oct 2020

PMID: 33037133