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

BioPAN: a web-based tool to explore mammalian lipidome metabolic pathways on LIPID MAPS.
Gaud C, C Sousa B, Nguyen A, Fedorova M, Ni Z, O'Donnell VB, Wakelam MJO, Andrews S, Lopez-Clavijo AF

Lipidomics increasingly describes the quantitation using mass spectrometry of all lipids present in a biological sample.  As the power of lipidomics protocols increase, thousands of lipid molecular species from multiple categories can now be profiled in a single experiment.  Observed changes due to biological differences often encompass large numbers of structurally-related lipids, with these being regulated by enzymes from well-known metabolic pathways.  As lipidomics datasets increase in complexity, the interpretation of their results becomes more challenging.  BioPAN addresses this by enabling the researcher to visualise quantitative lipidomics data in the context of known biosynthetic pathways.  BioPAN provides a list of genes, which could be involved in the activation or suppression of enzymes catalysing lipid metabolism in mammalian tissues.

+ View Abstract

F1000Research, 10, 1, 2021

PMID: 33564392

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 CS, Fedorova M, Feussner I, Griffiths WJ, Köfeler H, Merrill AH, Murphy RC, O'Donnell VB, Oskolkova O, Subramaniam S, Wakelam MJO, Spener F

A comprehensive and standardized system to report lipid structures analyzed by MS 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-labeled compounds in metabolic labeling 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.

+ View Abstract

Journal of lipid research, 61, 12, Dec 2020

PMID: 33531235

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 CS, Fedorova M, Feussner I, Griffiths WJ, Köfeler H, Merrill AH, Murphy RC, O'Donnell VB, Oskolkova O, Subramaniam S, Wakelam MJO, Spener F

A comprehensive and standardized system to report lipid structures analyzed by MS 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-labeled compounds in metabolic labeling 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.

+ View Abstract

Journal of lipid research, 61, 12, Dec 2020

PMID: 33455701