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 to serve as the director of the 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 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.

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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 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 of lipid second came from the United States that, under the Birmingham; the effects remained visible messengers, by using newly developed leadership of Ed Dennis at the University throughout his time at the Babraham MS-based techniques to characterize of California San Diego, the large project Institute. He participated in two clinical the build-up and breakdown of lipid Lipid Metabolites and Pathways Strategy trials in the Cancer Studies Unit at molecular species serving as intracellular (LIPID MAPS) had been funded, a new Birmingham. His publications clearly show second messengers. In the 1990s, his group undertaking began, which evolved into that he felt that knowledge from basic published a series of important articles on an internationally accepted classification biology and biochemistry with cultured observations that diacylglycerols acting as system and structure database (LMSD). In cells and other models are prerequisites for second messengers not only are derived response to this event, with crucial help understanding metabolism in health and from inositol lipid hydrolysis but also are from Michael, the Directorate General 12 of disease. In addition, the vast professional highly dependent on phospholipase D– the European Union was convinced to solicit network that he established over the years mediated cleavage of phosphatidylcholine, a applications for a large collaborative project and the instrumental facilities that he had textbook pathway taught to all biochemistry in the area of high-throughput analysis available enabled him to address a variety students today. of lipids and lipid–protein interactions of aspects in cancer research and viral In 1993, Michael was appointed as a in mammalian cells. Michael’s group and infectious diseases. professor of molecular pharmacology 20 more from academia and industry Michael, usually together with colleagues at the Institute for Cancer Studies at the joined the then-successful application for from his lab, was also a prolific writer of University of Birmingham, where he the LipidomicNet project. The project, reviews reflecting his main competences, intensified the use of MS. He reported his centred on lipid droplets and lipidomics such as PI-related metabolism and aspects many impressive results at conferences, technology including bioinformatics, began of cancer as well as lipidomics. Moreover, notably that the direction of PI action in 2008. Michael and others within the his lipidomics activities ranged from depends heavily on the chemical structure project were dubbed ‘the Viennese Coffee bioinformatics concerns to cutting-edge of the constituent fatty acids in the PI Club’ by the coordinator because of their MS methods (J. Clark et al. Nat. Methods molecule. In this respect, for Michael, a sometimes diverging opinions, which led to 8, 267–272; 2001) for the quantification of

Nature Metabolism | VOL 2 | June 2020 | 478–480 | www.nature.com/natmetab 479 obituary phosphatidylinositol (3,4,5)-trisphosphate aging through the human lifecycle. This effect and scarcely ever overruled others. molecular species in cells and tissues. aim brings together many of the scientific Michael was very much looking forward to Finally, Michael, together with Valerie strengths of the institute in a holistic view retiring from his position as director, not O’Donnell and colleagues, steadily promoted of how cellular and molecular processes only to spend more time with his beloved the maintenance and advancement of the change over the life course. Fifth, Michael family but also to return to the students LIPID MAPS project. was critically involved in setting up the and postdocs in his lab and to share his love EU-LIFE multinational European initiative, of science and lipidomics with them. This Babraham initiatives an alliance of 14 leading biomedical aspect is where the loss of Michael feels When Michael became the director of institutes involved in discussions on science, particularly cruel; we greatly empathized the Babraham Institute on the Babraham funding, best practices, staff exchanges with Michael’s looking forward to having Research Campus in Cambridge in 2007, the and collaboration. This effort has brought fun in the lab again after years of hard institute’s focus since the new millennium much-needed European and international work in looking after so many people at had been on basic biomedical molecular and exchange among biomedical communities, Babraham and internationally. We will miss cell biology, specifically signalling (where and has yielded new tangible outcomes, such him as a friend and a colleague; already, Michael’s research fit in), immunology as the EU LifeTime initiative. we are thinking: what would Michael have and epigenetics. Beyond his scientific said, or what would Michael have done? achievements, Michael had a major impact Colleague and mentor These thoughts will be with us for a very as director, making invaluable contributions In all his dealings, Michael was the same long time. ❐ to the well-being and growth of the institute. Michael to everyone and in that sense First, and most importantly, he built an was a man of the people. He would talk Friedrich Spener 1,2 ✉ , inclusive and diverse culture in the institute to everyone, preferably in person rather Christian Wolfrum 3 ✉ (as evidenced, for example, by two Athena than by phone or e-mail, and in doing so and 4,5,6 ✉ Swan silver awards), where everyone, got part of his daily exercise by shooting 1Institute of Molecular Biosciences, University of including PhD students, was able to share across the Babraham campus in his unique Graz, Graz, Austria. 2Division of Molecular Biology in the fun of science and science culture. half-walking/half-running style. On Friday and Biochemistry, Gottfried Schatz Research Second, he built superb core facilities that evenings at 5:30, he could often be found at Center, Medical University of Graz, Graz, Austria. continually sought to acquire cutting-edge the campus bar, having a pint with people 3Department of Health Science and Technology, technologies and the machinery needed. from stores, health and safety, and security. ETH Zürich, Schwerzenbach, Switzerland. Third, he worked with the government He was always interested in hearing others’ 4Epigenetics Programme, Babraham Institute, and Biotechnology and Biological Sciences thoughts, be they about family, politics, Cambridge, UK. 5Wellcome Sanger Institute, Research Council in a major expansion articles accepted or research grants awarded, Hinxton, Cambridge, UK. 6Centre for Trophoblast of the Babraham Research Campus; the in which case he was always very pleased for Research, University of Cambridge, Cambridge, UK. science minister at the time inaugurated people. He loved his family—his wife, Jane, ✉e-mail: [email protected]; the investment, and the campus is now one and his two sons, Alex and Patrick—and he [email protected]; of Europe’s largest of its kind and uniquely proudly talked about their achievements and [email protected] has a thriving research institute at its centre. progress in life. Fourth, because every institute funded with His enthusiasm and positive energy were Published online: 4 June 2020 taxpayer money must have a reason to exist, there for everyone to benefit from. In his https://doi.org/10.1038/s42255-020-0220-y Michael developed the current mission, decision-making, he was a consensus seeker Acknowledgements which encompasses research on healthful who used his emotional intelligence to great We thank S. Cook for guidance and help with the text.

480 Nature Metabolism | VOL 2 | June 2020 | 478–480 | www.nature.com/natmetab