Life Sciences Research for Lifelong Health

Michael Wakelam

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

Deciphering lipid structures based on platform-independent decision rules.
Hartler J, Triebl A, Ziegl A, Trötzmüller M, Rechberger GN, Zeleznik OA, Zierler KA, Torta F, Cazenave-Gassiot A, Wenk MR, Fauland A, Wheelock CE, Armando AM, Quehenberger O, Zhang Q, Wakelam MJO, Haemmerle G, Spener F, Köfeler HC, Thallinger GG

We achieve automated and reliable annotation of lipid species and their molecular structures in high-throughput data from chromatography-coupled tandem mass spectrometry using decision rule sets embedded in Lipid Data Analyzer (LDA; http://genome.tugraz.at/lda2). Using various low- and high-resolution mass spectrometry instruments with several collision energies, we proved the method's platform independence. We propose that the software's reliability, flexibility, and ability to identify novel lipid molecular species may now render current state-of-the-art lipid libraries obsolete.

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Nature methods, , 1548-7105, , 2017

PMID: 29058722

Dietary restriction protects from age-associated DNA methylation and induces epigenetic reprogramming of lipid metabolism.
Hahn O, Grönke S, Stubbs TM, Ficz G, Hendrich O, Krueger F, Andrews S, Zhang Q, Wakelam MJ, Beyer A, Reik W, Partridge L

Dietary restriction (DR), a reduction in food intake without malnutrition, increases most aspects of health during aging and extends lifespan in diverse species, including rodents. However, the mechanisms by which DR interacts with the aging process to improve health in old age are poorly understood. DNA methylation could play an important role in mediating the effects of DR because it is sensitive to the effects of nutrition and can affect gene expression memory over time.

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Genome biology, 18, 1474-760X, 56, 2017

PMID: 28351387

Autotaxin-lysophosphatidic acid receptor signalling regulates hepatitis C virus replication.
Farquhar MJ, Humphreys IS, Rudge SA, Wilson GK, Bhattacharya B, Ciaccia M, Hu K, Zhang Q, Mailly L, Reynolds GM, Aschcroft M, Balfe P, Baumert TF, Roessler S, Wakelam MJ, McKeating JA

Chronic hepatitis C is a global health problem with an estimated 170 million HCV infected individuals at risk of progressive liver disease and hepatocellular carcinoma (HCC). Autotaxin (ATX) is a phospholipase with diverse roles in physiological and pathological processes including inflammation and oncogenesis. Clinical studies have reported increased ATX expression in chronic hepatitis C, however, the pathways regulating ATX and its role in the viral life cycle are not well understood.

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Journal of hepatology, , 1600-0641, , 2017

PMID: 28126468

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Keywords

ageing
cell biology
lipids
signalling

Group Members

Latest Publications

Deciphering lipid structures based on platform-independent decision rules.

Hartler J, Triebl A, Ziegl A

Nature methods
1548-7105: (2017)

PMID: 29058722

Autotaxin-lysophosphatidic acid receptor signalling regulates hepatitis C virus replication.

Farquhar MJ, Humphreys IS, Rudge SA

Journal of hepatology
1600-0641: (2017)

PMID: 28126468

Runx1 Orchestrates Sphingolipid Metabolism and Glucocorticoid Resistance in Lymphomagenesis.

Kilbey A, Terry A, Wotton S

Journal of cellular biochemistry
118 1097-4644:1432-1441 (2017)

PMID: 27869314

Using lipidomics analysis to determine signalling and metabolic changes in cells.

Nguyen A, Rudge SA, Zhang Q

Current opinion in biotechnology
43 1879-0429:96-103 (2017)

PMID: 27816901

Insulin resistance uncoupled from dyslipidemia due to C-terminal PIK3R1 mutations.

Huang-Doran I, Tomlinson P, Payne F

JCI insight
1 :e88766 (2016)

PMID: 27766312

The Phospholipase D2 Knock Out Mouse Has Ectopic Purkinje Cells and Suffers from Early Adult-Onset Anosmia.

Vermeren MM, Zhang Q, Smethurst E

PloS one
11 1932-6203:e0162814 (0)

PMID: 27658289

C13orf31 (FAMIN) is a central regulator of immunometabolic function.

Cader MZ, Boroviak K, Zhang Q

Nature immunology
1529-2916: (2016)

PMID: 27478939

Purification, characterization and crystallization of the F-ATPase from Paracoccus denitrificans.

Morales-Rios E, Watt IN, Zhang Q

Open biology
5 2046-2441: (2015)

PMID: 26423580