obituary Michael John Owen Wakelam 1955–2020 We have lost a distinguished biochemist who dedicated his career to the study of phosphatidylinositol signalling in metabolic regulation and to the advancement of lipidomics. ichael John Owen Wakelam passed away on 31 March, 2020 at the Mage of 64, much too early. He became known to colleagues and friends as a scientist highly regarded for his research. He was honoured in 2018 with the Morton Lectureship of the Biochemical Society and was elected a fellow of the Royal Society of Biology. In 2019, he was elected a member of the Academia Europaea. Academic career It was not by chance that Michael turned his focus to phosphatidylinositols (PIs) and lipid signalling. He was a student and later a professor at the University of Birmingham at a time when Britain was the world’s hub of pioneering phospholipid research, such as that by J. N. Hawthorne and Bob Michell on PI in Birmingham. Bob Michell inspired Michael extraordinarily, and they even published a joint review. Subsequently, Michael moved to Cambridge to serve as the director of the Babraham Institute, where Credit: Babraham Institute Rex Dawson and Robin Irvine studied phospholipids, particularly PI metabolism and signalling. A joint publication by Michael and Irvine appeared as well. the Babraham Institute, and he received an the Keystone Symposia on Molecular and Certainly, Michael’s scientific engagement honorary professorship in lipid signalling at Cellular Biology. can be seen in the tradition of these eminent the University of Cambridge Clinical School. phospholipid scientists. In addition, he was an honorary professor Lipid signalling and metabolism Michael’s career path is impressive. at Birmingham University and a visiting Notably, Michael’s research did not begin He received his BS degree in medical professor at King’s College London. with lipids; the subject of his PhD thesis, biochemistry in 1977 and his PhD in Michael’s research spanned more than under the supervision of Deryck Walker biochemistry in 1980 from the University four decades, and one of its core aims was at the University of Birmingham, was the of Birmingham. From 1981 to 1983, he was to advance understanding of the roles and inducible expression of hepatic glucokinase. a postdoctoral fellow at the University of regulation of lipid signalling pathways in As a postdoctoral associate at the Faculty Konstanz in Germany, and he then spent a inflammation and cancer, with an emphasis of Biology at the University of Konstanz, he further 2 years as a Beit Memorial Research on PI molecules. A major focus of his lab worked with Dirk Pette, who was a specialist Fellow at Imperial College London. In at the Babraham Institute was the use and in glycolytic enzymes, in the tradition of 1985, he was offered a position as a lecturer development of lipidomics methodologies Theodor Bücher from Munich, but who in biochemistry at Glasgow University, for determining the functions of individual focused on muscle biology at the University where was promoted to reader and stayed lipid molecular species and their application of Konstanz. Michael’s first articles at the until 1993. The University of Birmingham in identifying novel targets for therapeutic University of Konstanz were on the control asked him to come ‘back home’ to take up intervention. Michael’s scientific work of glucose 1,6-bisphosphate by various a professorship in molecular pharmacology was published in more than 230 original effectors in cultured muscle cells, and he at the Institute for Cancer Studies, where articles and reviews, and he was a arrived, obviously inspired by Michell’s he remained until 2006. During that time, much-sought-after speaker at international thinking, at PI breakdown in the course of he was the associate dean of the School of meetings. In addition, he undertook myoblast fusion. This research culminated Medicine from 2003 to 2006, and between editorial duties for several top lipid journals in an article showing that cation channels in 2004 and 2007, he was the chair of the (BBA Molecular and Cell Biology of Lipids, cultured embryonic skeletal cells are sensitive Medical Research Council Molecular the Journal of Lipid Research and Current to a neurotransmitter-like action of ATP and Cellular Medicine Board, as well as a Opinion in Pharmacology) and served on (H. A. Kolb and M. J. O Wakelam, Nature member of the Medical Research Council. the steering committee for the International 303, 621–623; 1983). The article not only On the basis of all these accomplishments, in Conferences for the Bioscience of Lipids represents Michael’s entry into the PI field 2007, Michael was chosen as the director of and on the scientific advisory board for but also is his first investigation of signalling. 478 NATURE METABOLISM | VOL 2 | JUNE 2020 | 478–480 | www.nature.com/natmetab obituary After he joined Imperial College key species was phosphatidylinositol-4’,5′ spirited yet always fruitful discussions. For London, he collaborated with Chris bisphosphate. He found that hydrolysis by example, Viennese Coffee Club members Marshall and Alan Hall at the Institute of phospholipase C produces polyunsaturated at one point became irritated by literature Cancer Research, and his interest in signal diacylglycerol species, whereas hydrolysis reporting incorrect MS data; that is, the transduction was strengthened when he by phospholipase D generates saturated/ levels of structural elucidation that were turned his focus to PI metabolism in relation monounsaturated phosphatidic acid claimed for lipid species were inconsistent to ras oncogenes. This work, as well as species. The former activate protein with the instrument resolving power. the research conducted afterwards in the kinase C, and the latter, among other Consequently, a shorthand annotation for Molecular Pharmacology Group at the functions, activate the formation of actin the correct presentation of lipid MS data was Department of Biochemistry at Glasgow stress fibres. His group demonstrated that, developed, and an article was published in University, was pivotal to his contributions with the help of two enzymes, saturated/ 2013, with Michael as senior author. This to the fields of lipid signalling and lipid monounsaturated diacylglycerols and annotation was subsequently adopted by second messengers. Two publications polyunsaturated phosphatidic acid species the International Lipid Classification and in 1986 are especially noteworthy, given are produced yet are metabolically inactive. Nomenclature Committee (ILCNC). their tremendous impact on the scientific This work was published 1997 and The LipidomicNet project clearly community. One article, a collaborative provided ample evidence of the messenger strengthened relations across the Atlantic. effort with colleagues from London and concept put forward by Michael. From European colleagues, including Michael, Glasgow, demonstrates that p21 N-Ras is this and other publications, it is clear were asked to join the ILCNC and were one of the signalling hubs responsible for that Michael’s experimental approach co-authors of the two fundamental the formation of a phosphatidylinositol increasingly transitioned from thin classification articles published in 2005 and trisphosphate signal. The second article layer chromatography, elaborate liquid 2009. However, by 2013, the LipidomicNet examines signalling via the glucagon chromatography and radioactive-tracer grant from the European Union had ended, receptor and shows that glucagon, at low methods to high-end MS. His pertinent and the long-running LIPID MAPS grant physiological concentrations, causes PI publication (T. R. Pettitt, S. K. Dove, A. in the United States was also coming to an breakdown with production of inositol Lubben, S. D. J. Calaminus and M. J. O. end. Luckily, Michael from the Babraham phosphates and independently stimulates Wakelam, J. Lipid Res. 47, 1588–1596; 2006) Institute and Valerie O’Donnell from Cardiff adenylate cyclase activity, putatively is a seminal article on how to analyse the University teamed up with Ed Dennis and through two glucagon receptors. entire cascade of PI-phosphate species Shankar Subramaniam from the University Interestingly, more than 30 years with simpler liquid chromatography in of California San Diego and secured a later, the concept of the dual mode of combination with MS. follow-up LIPID MAPS grant from the glucagon-receptor signalling resurfaced Wellcome trust in 2017. This funding when the structure of the glucagon receptor Engagement for lipidomics was a major relief, and it has safeguarded was analysed in greater depth. In 2007, Michael started as the director and enabled further development of an Towards the end of his time in the of the Babraham Institute, which was informative website, webinars and biochemistry lab at Glasgow University, well suited for his broad interests and his valuable databases. Michael began to appreciate the penchant for accompanying technologies. Michael’s scientific horizons and importance of mass spectrometry (MS) The flourishing of lipidomics in Europe sensibilities were profoundly shaped for understanding the different molecular owes much to Michael’s foresight and by his time as a young professor of structures of a lipid in terms of its function. activities. Editorials in lipidomics journals molecular pharmacology in the oncology As a result, Michael’s subsequent work appeared in Europe in 2003, but when news research environment at the University of expanded on the roles