Philip Cohen (British biochemist)

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Sir
Philip Cohen
FRS FRSE FMedSci
Born (1945-07-22) 22 July 1945 (age 79)
Middlesex, England
Education University College London
Known forresearch into protein phosphorylation
SpouseTricia Cohen
Awards
Scientific career
Fieldsprotein phosphorylation
Institutions University of Dundee
Doctoral advisor Michael Rosemeyer
Notable students Dario Alessi, Claire E. Eyers
Website www.lifesci.dundee.ac.uk/people/philip-cohen

Sir Philip Cohen (born 22 July 1945) is a distinguished English biochemist known for his extensive contributions to the field of biochemistry, especially to the understanding of the role of reversible protein phosphorylation in cell regulation. [4]

Contents

Early life and education

Cohen was born on 22 July 1945. After attending Hendon County Grammar School in North London from 1956 to 1963, he pursued a B.Sc. in Biochemistry at University College London, graduating with 1st Class Honours in 1966. [5]

Research and career

Cohen continued at University College London and obtained his PhD in Biochemistry in 1969 under the guidance of Dr. Michael A. Rosemeyer. His thesis was entitled "The Subunits of Glucose-6-Phosphate Dehydrogenase". Cohen's early postdoctoral work was supported by an SRC-NATO Postdoctoral Fellowship, allowing him to collaborate with Professor Edmond H. Fischer at the University of Washington in Seattle from 1969 to 1971. [6]

In 1971, Cohen returned to the UK, taking up a Lecturer position in the Department of Biochemistry at the University of Dundee. This was a position he held until December 1978. During this period, he also received a Wellcome Trust Special Research Fellowship from January 1976 to December 1978. His career at Dundee saw a series of promotions: he became a Reader in the Department of Biochemistry in 1978, and by 1981, he was appointed Professor of Enzymology. [7]

Cohen's contributions to the field were recognized by the Royal Society, which appointed him as a Research Professor at the University of Dundee from October 1984 to September 2010. His leadership roles expanded over the years, with him directing the Medical Research Council Protein Phosphorylation Group from 1983 to 1989, the Medical Research Council Protein Phosphorylation Unit from 1990 to March 2012 [8] and the Scottish Institute for Cell Signalling from 2008 until 2012. [9] He reverted to his original position as Professor of Enzymology at the School of Life Sciences, University of Dundee, from April 2012 onwards. His expertise also brought him to the international stage, serving as a Vallee Visiting Professor at Harvard Medical School since November 2013. [10]

Cohen played a pivotal role in forming the Division of Signal Transduction Therapy in July 1998, co-directoring it with Sir Peter Downes until June 2012 and continuing as its deputy director until 2022. [11]

In 2023, Cohen and his family set up the Tricia Cohen Memorial Trust (TCMT) to provide PhD studentships in memory of his late wife and colleague Tricia to whom he was married for over 50 years. [12]

Awards and recognition

Cohen was elected a Member of the European Molecular Biology Organisation in 1982 and subsequently became a Fellow of the Royal Societies of both London and Edinburgh in 1984. He received the CIBA Medal and Prize (now the Novartis Medal and Prize) from the British Biochemical Society in 1992. [13] In the 1990s he won prizes such as the Prix Van Gysel of the Belgian Royal Academies of Medicine, the Bruce-Preller Prize of the Royal Society of Edinburgh, the Pfizer Innovation Award for Europe [14] , and the Louis Jeantet Prize for Medicine. [15]

He was knighted by Queen Elizabeth II in 1998 for "Services to Biochemistry". [16] He also received honors, including the Sir Hans Krebs Medal of the Federation of European Biochemical Societies, the Bristol-Myers Squibb Distinguished Achievement Award [17] [18] , the Debrecen Award for Molecular Medicine and the Rolf Luft Award of the Karolinska Institute, Sweden. [19] [20] He was also recognised as the World's second-most cited scientist in "Biology and Biochemistry" from 1992 to 2003  and received Royal Medals from both the Royal Society of Edinburgh (2004) and Royal Society of London (2008). [21] [22]

Cohen has been appointed as a Foreign Associate of the National Academy of Sciences of the USA in 2008 National Academy of Sciences and a Fellow of the American Society for Microbiology in 2009. His lifetime contributions were acknowledged with the MRC Millenium Medal in 2013, the Albert Einstein World Award of Science in 2014, and recipient of the Lifetime Achievement Award from Scotland's Life Sciences Industry and The Herald Higher Education Lifetime Achievement Award in 2023. [23]

Notable Contributions

Cohen has made advances to the understanding of how protein phosphorylation and dephosphorylation events regulate cell life, His contributions include the dissection of a major part of the insulin signal transduction pathway, [24] the classification of protein phosphatases and identification of mechanisms that regulate their biological functions, and the dissection of mitogen-activated protein kinase cascades. [25] Sir Philip also developed large panels of protein kinases to profile the specificities of protein kinase inhibitors that have been used widely in the development of kinase-inhibiting drugs and to study the roles of protein kinases in cell regulation. Since 2008 his research has focused on how the interplay between protein phosphorylation and protein ubiquitylation regulates innate immunity. Earlier in his career he also made several contributions to the understanding of how glycogen molecules are synthesized de novo and the molecular mechanisms that trigger the mobilisation of glycogen. Some notable examples of his publications on these topics are the following:

Related Research Articles

<span class="mw-page-title-main">Phosphorylation</span> Chemical process of introducing a phosphate

In biochemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology. Protein phosphorylation often activates many enzymes.

<span class="mw-page-title-main">Glucose 6-phosphate</span> Chemical compound

Glucose 6-phosphate is a glucose sugar phosphorylated at the hydroxy group on carbon 6. This dianion is very common in cells as the majority of glucose entering a cell will become phosphorylated in this way.

<span class="mw-page-title-main">Insulin receptor</span> Cell receptor found in humans

The insulin receptor (IR) is a transmembrane receptor that is activated by insulin, IGF-I, IGF-II and belongs to the large class of receptor tyrosine kinase. Metabolically, the insulin receptor plays a key role in the regulation of glucose homeostasis; a functional process that under degenerate conditions may result in a range of clinical manifestations including diabetes and cancer. Insulin signalling controls access to blood glucose in body cells. When insulin falls, especially in those with high insulin sensitivity, body cells begin only to have access to lipids that do not require transport across the membrane. So, in this way, insulin is the key regulator of fat metabolism as well. Biochemically, the insulin receptor is encoded by a single gene INSR, from which alternate splicing during transcription results in either IR-A or IR-B isoforms. Downstream post-translational events of either isoform result in the formation of a proteolytically cleaved α and β subunit, which upon combination are ultimately capable of homo or hetero-dimerisation to produce the ≈320 kDa disulfide-linked transmembrane insulin receptor.

<span class="mw-page-title-main">GSK-3</span> Class of enzymes

Glycogen synthase kinase 3 (GSK-3) is a serine/threonine protein kinase that mediates the addition of phosphate molecules onto serine and threonine amino acid residues. First discovered in 1980 as a regulatory kinase for its namesake, glycogen synthase (GS), GSK-3 has since been identified as a protein kinase for over 100 different proteins in a variety of different pathways. In mammals, including humans, GSK-3 exists in two isozymes encoded by two homologous genes GSK-3α (GSK3A) and GSK-3β (GSK3B). GSK-3 has been the subject of much research since it has been implicated in a number of diseases, including type 2 diabetes, Alzheimer's disease, inflammation, cancer, addiction and bipolar disorder.

Glycogenesis is the process of glycogen synthesis or the process of converting glucose into glycogen in which glucose molecules are added to chains of glycogen for storage. This process is activated during rest periods following the Cori cycle, in the liver, and also activated by insulin in response to high glucose levels.

<span class="mw-page-title-main">Edmond H. Fischer</span> American-Swiss biochemist (1920–2021)

Edmond Henri Fischer was a Swiss-American biochemist. He and his collaborator Edwin G. Krebs were awarded the Nobel Prize in Physiology or Medicine in 1992 for describing how reversible phosphorylation works as a switch to activate proteins and regulate various cellular processes. From 2007 until 2014, he was the Honorary President of the World Cultural Council. At the time of his death at age 101 in 2021, he was the oldest living Nobel Prize laureate.

<span class="mw-page-title-main">Glycogen phosphorylase</span> Class of enzymes

Glycogen phosphorylase is one of the phosphorylase enzymes. Glycogen phosphorylase catalyzes the rate-limiting step in glycogenolysis in animals by releasing glucose-1-phosphate from the terminal alpha-1,4-glycosidic bond. Glycogen phosphorylase is also studied as a model protein regulated by both reversible phosphorylation and allosteric effects.

<span class="mw-page-title-main">Glycogen synthase</span> Enzyme class, includes all types of glycogen/starch synthases

Glycogen synthase is a key enzyme in glycogenesis, the conversion of glucose into glycogen. It is a glycosyltransferase that catalyses the reaction of UDP-glucose and n to yield UDP and n+1.

<span class="mw-page-title-main">Richard Henderson (biologist)</span> British biologist (born 1945)

Richard Henderson is a British molecular biologist and biophysicist and pioneer in the field of electron microscopy of biological molecules. Henderson shared the Nobel Prize in Chemistry in 2017 with Jacques Dubochet and Joachim Frank. "Thanks to his work, we can look at individual atoms of living nature, thanks to cryo-electron microscopes we can see details without destroying samples, and for this he won the Nobel Prize in Chemistry."

The Division of Signal Transduction Therapy or DSTT is an organization managed by the University of Dundee, the Medical Research Council, and the pharmaceutical companies AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Merck Serono, Janssen Pharmaceutica, and Pfizer. The purpose of the collaboration is to conduct cell signalling research and to encourage development of new drug treatments for global diseases such as cancer, rheumatoid arthritis, and Parkinson's disease. Specifically the collaboration aims to target protein kinases and the ubiquitylation system in the development of these therapies. It is one of the largest ever collaborations between the commercial pharmaceutical industry and any academic research institute.

Nicholas Kester Tonks FRS is a professor in Cold Spring Harbor Laboratory. His research is mainly focused on studying the function and regulation of protein tyrosine phosphatases.

<span class="mw-page-title-main">Protein phosphatase 1</span>

Protein phosphatase 1 (PP1) belongs to a certain class of phosphatases known as protein serine/threonine phosphatases. This type of phosphatase includes metal-dependent protein phosphatases (PPMs) and aspartate-based phosphatases. PP1 has been found to be important in the control of glycogen metabolism, muscle contraction, cell progression, neuronal activities, splicing of RNA, mitosis, cell division, apoptosis, protein synthesis, and regulation of membrane receptors and channels.

<span class="mw-page-title-main">Vanadyl acetylacetonate</span> Chemical compound

Vanadyl acetylacetonate is the chemical compound with the formula VO(acac)2, where acac– is the conjugate base of acetylacetone. It is a blue-green solid that dissolves in polar organic solvents. The coordination complex consists of the vanadyl group, VO2+, bound to two acac– ligands via the two oxygen atoms on each. Like other charge-neutral acetylacetonate complexes, it is not soluble in water.

Dario Renato Alessi is a French-born British biochemist, Director of the Medical Research Council Protein Phosphorylation and Ubiquitylation Unit and Professor of Signal Transduction, at the School of Life Sciences, University of Dundee.

David Barford is a British medical researcher and structural biologist at the MRC Laboratory of Molecular Biology Cambridge, UK.

The Portland Press Excellence in Science Award was an annual award instituted in 1964 to recognize notable research in any branch of biochemistry undertaken in the UK or Republic of Ireland. It was initially called the CIBA Medal and Prize, then the Novartis Medal and Prize. The prize consists of a medal and a £3000 cash award. The winner is invited to present a lecture at a Society conference and submit an article to one of the Society's publications. Notable recipients include the Nobel laureates John E. Walker, Paul Nurse, Sydney Brenner, César Milstein, Peter D. Mitchell, Rodney Porter, and John Cornforth.

The School of Life Sciences at the University of Dundee conducts research into the molecular and cellular mechanisms underlying human health and disease.

<span class="mw-page-title-main">Claire E. Eyers</span> British biological mass spectrometrist

Claire Eyers is a British biological mass spectrometrist who is professor of biological mass spectrometry at the University of Liverpool, where she heads up the Centre for Proteome Research. Her research publications list her either as Claire E Haydon or Claire E Eyers.

Miratul Muqit FRSE FMedSci is a British neurologist and a Programme Lead at the MRC Protein Phosphorylation and Ubiquitylation Unit (MRCPPU) in the School of Life Sciences at the University of Dundee. His research focuses on the study of the PINK1 gene, mutations in which are a major cause of Parkinson's disease.

<span class="mw-page-title-main">Hagit Eldar-Finkelman</span> Israeli biochemist

Hagit Eldar-Finkelman is an Israeli scientist and a principal investigator of an active research laboratory at the Sackler School of Medicine at Tel Aviv University. Eldar-Finkelman’s research is focused on the signal transduction field and drug development targeting protein kinases. She is well known for her pioneering work on the functions of GSK-3 and its contribution to diabetes and other pathogenies, including depressive behavior, Alzheimer’s diseases, and Huntington’s diseases. Novel findings also include the unique evolution of GSK-3 isozymes. Eldar-Finkelman is a leading figure in developing novel substrate competitive inhibitors (SCIs) for GSK-3 with significant benefits as drug candidates.

References

  1. ↑ Cohen, P (1979). "The hormonal control of glycogen metabolism in mammalian muscle by multivalent phosphorylation". Biochemical Society Transactions. 7 (3): 459–80. doi:10.1042/bst0070459. PMID   221283.
  2. ↑ Louis-Jeantet Prize
  3. ↑ "The Royal Society of Edinburgh Royal Medals" . Retrieved 8 June 2019.
  4. ↑ "Philip Cohen". royalsociety.org. Retrieved 25 December 2023.
  5. ↑ "Principal Investigator | Philip Cohen | MRC PPU". www.ppu.mrc.ac.uk. Retrieved 25 December 2023.
  6. ↑ "cell.com" (PDF).
  7. ↑ "Principal Investigator | Philip Cohen". www.ppu.mrc.ac.uk. Retrieved 25 December 2023.
  8. ↑ "mrc.ukri.org".
  9. ↑ "Follow the money: Scotland funds a brain gain". Science|Business. Retrieved 25 December 2023.
  10. ↑ "Sir Philip Cohen, PhD". thevalleefoundation.org. Retrieved 25 December 2023.
  11. ↑ "Philip Cohen". The Conversation. 31 January 2017. Retrieved 25 December 2023.
  12. ↑ "Welcome to The Tricia Cohen Memorial Trust". The Tricia Cohen Memorial Trust. Retrieved 25 December 2023.
  13. ↑ "Excellence in Science Award". www.biochemistry.org. Retrieved 25 December 2023.
  14. ↑ "The Pfizer Award 1999 | MRC PPU". www.ppu.mrc.ac.uk. 31 October 1999. Retrieved 25 December 2023.
  15. ↑ admin (17 September 2017). "The Louis-Jeantet Prizes | Jeantet" . Retrieved 25 December 2023.
  16. ↑ "Sir Philip Cohen, PhD | The Vallee Foundation". thevalleefoundation.org. Retrieved 25 December 2023.
  17. ↑ "Bristol-Myers Squibb Award | MRC PPU". www.ppu.mrc.ac.uk. 1 October 2002. Retrieved 25 December 2023.
  18. ↑ "OUH - News archive". www.ous-research.no. Retrieved 25 December 2023.
  19. ↑ "Debrecen Award for Molecular Medicine 2004 | Faculty of Medicine". aok.unideb.hu. Retrieved 25 December 2023.
  20. ↑ "Philip Cohen Receives Prestigious Rolf Luft Award in Stockholm, Sweden | MRC PPU". www.ppu.mrc.ac.uk. 3 October 2006. Retrieved 25 December 2023.
  21. ↑ "Sir Philip Cohen, PhD | The Vallee Foundation". thevalleefoundation.org. Retrieved 25 December 2023.
  22. ↑ "Lifetime Achievement Award for Professor Sir Philip Cohen | Welcome to Bio-Dundee". www.biodundee.co.uk. Retrieved 25 December 2023.
  23. ↑ "Professor Sir Philip Cohen Receives MRC Millennium Medal". Proteomics & Metabolomics from Technology Networks. Retrieved 25 December 2023.
  24. ↑ De Meyts, Pierre (2000), Feingold, Kenneth R.; Anawalt, Bradley; Blackman, Marc R.; Boyce, Alison (eds.), "The Insulin Receptor and Its Signal Transduction Network", Endotext, South Dartmouth (MA): MDText.com, Inc., PMID   27512793 , retrieved 25 December 2023
  25. ↑ "Philip Cohen". royalsociety.org. Retrieved 25 December 2023.
  26. ↑ Embi, N.; Rylatt, D. B.; Cohen, P. (June 1980). "Glycogen synthase kinase-3 from rabbit skeletal muscle. Separation from cyclic-AMP-dependent protein kinase and phosphorylase kinase". European Journal of Biochemistry. 107 (2): 519–527. doi: 10.1111/j.1432-1033.1980.tb06059.x . ISSN   0014-2956. PMID   6249596.
  27. ↑ Alessi, Dario R.; James, Stephen R.; Downes, C.Peter; Holmes, Andrew B.; Gaffney, Piers R.J.; Reese, Colin B.; Cohen, Philip (April 1997). "Characterization of a 3-phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase Bα". Current Biology. 7 (4): 261–269. doi: 10.1016/s0960-9822(06)00122-9 . ISSN   0960-9822. PMID   9094314.
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