Research output per year
Research output per year
Professor
TW20 0EX
A brief history: I graduated with a PhD in molecular cell biology at the University of Melbourne (Australia) in 1994, and pursed subsequent postdoctoral positions at St Andrews University and University College London (UCL) in the UK, followed by an independent Wellcome Trust Career Development fellowship at UCL. I moved to Royal Holloway University of London in 2006, where I am now Professor of Molecular Cell Biology and have been the Head of the Centre for Biomedical Sciences for 12 years, and I continue my research into areas of molecular cell biology, neuroscience, pharmacology, drug development, and pharmacogenetics through studies often using the social amoeba Dictyostelium, and then translating discoveries to relevant mammalian models.
Our research interests: I have a long-standing drive to improve the quality of life for people in our society, through better understanding the cellular basis of disease and by developing new therapeutic treatments. I often undertake an innovative approach for my research, by primarily employing a simple non-animal model for early stage research, called the social amoeba Dictyostelium (see here and imaged below), which allows a range of experiments not available using traditional (mammalian) models. Using this model provides both specific advantages in research, and contributes to developing animal replacement, reduction and refinement (3Rs) research approaches (see here).
Some central areas of my research are listed here:
Can we develop better treatments for Epilepsy: We have employed Dictyostelium as an advantageous model system to examine how treatments for epilepsy work at a cellular level (here, here, and here, and below image). We have then been able to identify new chemicals that may provide better or safer treatments for epilepsy using mammalian models. This long term project has been in close collaboration with Prof Matthew Walker (here), and with the US government agency (ETSP) (here). Highlights of this work include identifying how Valproic acid (valproate, Depakote, depakene) works in Dictyostelium (here, here, and here) and in the brain (here), leading to the identification of potential novel treatments for epilepsy (here, here, and here). Through this work, we have also identified a likely mechanism of a diet used in the treatment of drug resistant epilepsy in children, called the MCT ketogenic diet (here, here, here, here andhere). This advance is likely to have far-reaching effects on the field of drug resistant epilepsy research and ultimately patient treatment.
See also our Youtube movies: here and here
Key collaborators: Prof Matthew Walker (here)
Key industry partners: Vitaflo Ltd (here)
Evolutionary origins of the proteins involved in disease: Many proteins are highly conserved throughout evolution across distant species, suggesting key roles in cells that have been retained. Our group has investigated the conservation of function of several proteins, from our amoeba model to humans. The importance of this is two-fold: firstly, through establishing a conserved function of proteins across a million years of evolution, we provide evidence for essential function of that protein. Secondly, a conserved function enables us to investigate the role of the protein in cell function, or as a target for therapeutic drugs or natural products. Our research in this area has included several studies on a key group of proteins involved in Alzheimer’s disease (called the gamma secretase complex), where we have established a conserved cell function between Dictyostelium and human proteins (here, here, here), and identified roles of these proteins that may be involved in the damage caused in Alzheimer’s disease. Other conserved proteins include targets for bitter tasting chemicals (here).
Key collaborators: Dr Richard Killick, Prof Alan Kimmel
What cellular mechanisms underlie the basis of Bipolar disorder and its treatment: Bipolar disorder is a severe neuropsychiatric disorder that is treated with several drug that are also effective in the epilepsy (including lithium, valproic acid, carbamazepine). Our research has examined how these treatments function in cells, both in Dictyostelium and in mammalian neurons. We have provided key evidence to support a theory of bipolar disorder treatment (here, here, here), and new mechanism (here) and recently suggested a molecular target for this mechanism (here).
Natural products, medicines, and pharmacogenetics: Chemicals derived from plants provide an enormous potential for use as medical treatments. These chemicals include products commonly found in fruits (e.g. flavonoids) and thought to work as anti-oxidants, and products found in flowers or buds (e.g. cannabis)(below). We have used Dictyostelium to analyse many natural products to improve our understanding of how they may function in health and disease (here). Products include the flavonoids such as naringenin (here), food additives such as curcumin found in turmeric (here), cannabinoids used in medicine and others. By using Dictyostelium, we can identifying genes that control the function of these compounds, and from this help to describe how the compounds may function in maintaining good health or treating disease such as polycystic kidney disease (here), or cancer (here).
Molecular mechanisms underlying (bitter) taste: Understanding how we taste different food components remains largely unclear. Improving knowledge in this area is very important in medicine related to bitter taste, where unpalatable medicines provide a significant disadvantage in treatment. We have used Dictyostelium to address this issue, where we have been able to propose proteins in both the amoeba and humans that may provide the way we taste bitter compounds (here, here). We have also developed technology to identify novel compounds with bitter taste effects, without the use of animals (here), based upon monitoring changes in cells (imaged below over time).
Key collaborators: Prof Paul Andrews (here)
Key industry partners: GlaxoSmithKline (here)
Also see our Youtube movies: (here)
Some esteem indicators and recent note-worthy events:
• Member Executive Committee for the International Neurological Ketogenic Society (INKs) Dec 2017-
• Committee Member (Eukaryote; see here) UK Microbiology Society Jan 2018-21
• British Library (here) Debate, London, TalkScience@BL - Replace, Reduce, Refine: Animals in Research 2016
• Lead organiser, Dicty2105 (see here), the annual International Dictyostelium meeting 2015.
• Invited Symposium Convenor, Festival of Neuroscience (British Neuroscience Association), 2013 London, Edinburgh, 2015 (see here), 2021 (Online)
• Science Museum London (see here), Exhibitor, 2015.
• Invited participant Technology Strategy Board (TSB)/NC3Rs roadmapping workshop in Non-Animal Technologies UK, 2014
• Invited presenter, American Epilepsy Society International meeting, Washington DC 2013
• Invited Participant, Emerging Technologies and Industries Programme: Non-Animal Technologies, Royal Society 2013
• Invited Symposium Convenor, Festival of Neuroscience (British Neuroscience Association), Barbican Centre London, 2013
• Invited participant, House of Commons (UK) MPs and Peers luncheon focusing on Alternatives to Animals in Science – Replacing, Reducing and Refining, hosted by Lord Willis of Knaresborough, 2012
• Invited presenter, UK Home Office Research Day, 2011
• Invited presenter, International Workshop on the Neurobiology of Epilepsy 2011
• Invited participant, U.S. and European Animal-Research Regulations: Impact on Neuroscience Research workshop 2011
• Organiser, UK/EU Dictyostelium Annual conference 2011, Royal Holloway University of London
• Invited member: Dictyostelium International Science Advisory Board 2009, ongoing
• Invited presenter, Members of the European Parliament, 2009
• Principle organiser, Bipolar Disorder: Molecular and Cellular Biology Conference; Royal Holloway University of London, 2009
Current Research Group
Previous group members (PhD students and Postdoctoral Fellows - Finishing date and current position)
Publications (Total publications 69; of these 44 as last author and 12 as first author)
89. Schaf, Shinhmar, Zeng, Pardo, Beesley, Syed & Williams (2023) Enhanced Sestrin expression through Tanshinone 2A treatment improves PI3K-dependent inhibition of glioma growth. Cell Death Discov. 19;9(1):172. doi: 10.1038/s41420-023-01462-6.
88. Tayebi, Leon-Ricardo, McCall, Mehinovic, Engelstad, Huynh, Turner, Weisenberg, Thio, Hruz, Williams, De Vivo, Petit, Haller, Gurnett (2023) Quantitative determination of SLC2A1 variant functional effects in GLUT1 deficiency syndrome. Ann Clin Transl Neurol.10(5):787-801. doi: 10.1002/acn3.51767
87. Andrews, Williams, Sanger (2022) Anti-emetic effects of thalidomide: Evidence, mechanism of action, and future directions. Curr Res Pharmacol Drug Discov. 3:100138. doi: 10.1016/j.crphar.2022.100138. PMID: 36568268; PMCID: PMC9780081.
86. Heslop-Harrison, Goddard & Williams (2022) Mutation screening of Dictyostelium Restriction Enzyme-Mediated Integration (REMI) Libraries, Methods in Molecular Biology, submitted 26/11/2021. In press
875. Huber, Williams and Muller-Tubenberger (2022) Editorial: Dictyostelium: A Tractable Cell and Developmental Model in Biomedical Research, Frontiers in Cell and Developmental Biology, 10, doi: 10.3389/fcell.2022.909619
84. Williams, Boison, Masino and Rho (2022) Mechanisms of Ketogenic Diet Action. In Jasper’s Basic Mechanisms of the Epilepsies 5th Edition, Eds Nobels, Avoli, Rogawski, Vezzani and Delgado-Escueta, Publishers Oxford Medicines Online and NCBI Bookshelf. In Press
853. Storey, Williams, Fisher and Annesley (2022) Dictyostelium discoideum: A model system for neurological disorders, Cells, 11(3), 463. doi.org/10.3390/cells11030463
842. Williams*, Chubb, Insall, King, Pears, Thompson, Weijer (2021) Moving the research forward: The best of British biology using the tractable model system Dictyostelium discoideum. Cells, 10, 3036. https://doi.org/10.3390/cells10113036
81. Warren, Kramár, Lloyd-Jones & Williams (2021) Decanoic Acid Stimulates Autophagy in D. discoideum. Cells, 10(11), 2946, doi: 10.3390/cells10112946
80. Walker and Williams (2021) Identifying the Molecular Mechanism of the MCT (Ketogenic) Diet, in Ketogenic Diet and Metabolic therapies Ed Masino and Oxford University Press, doi: 10.1093/ med/ 9780197501207.001.0001
79. Klionsk et al (2021) Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition), Autophagy 17(1):1-382 (see here)
78. Pain, Shinhmar & Williams (2021) Using Dictyostelium to advance our understanding of the role of medium chain fatty acids in health and disease, Frontiers in Cell & Developmental Biology, 13, 9, 722066 (see here)
77. Schoeler, Orford, Vivekananda, Simpson, Van de Bor, Smith, Balestrini, Rutherford, Brennan, McKenna, Lambert, Barker, Jackson, Williams, Sisodiya, Eaton, Heales*, Cross*, Walker* (2021) K.Vita®: a feasibility study of a blend of medium chain triglycerides to manage drug-resistant epilepsy. Brain Communications, 3(4), fcab160, https://doi.org/10.1093/braincomms/fcab160
76. Damstra-Oddy, Warren, Perry, Desfougères, Fitzpatrick, Schaf, Costelloe, Hind, Downer, Saiardi, & Williams (2020) Phytocannabinoid-dependent mTORC1 regulation is dependent upon IPMK activity. British Journal of Pharmacology, 178:1149–1163 (see here)
75. Warren, Dooves, Lugarà, Damstra-Oddy, Schaf, Heine, Walker, & Williams (2020) Decanoic acid inhibits mTORC1 activity independent of glucose and insulin signalling, Proceedings of the National Academy of Science (PNAS), 117 (38) 23617-23625, (see here)
74. Yelshanskaya, Singh, Narangoda, Williams, Kurnikova, & Sobolevsky (2020) Structural basis of AMPA receptor inhibition by 4-BCCA, British Journal of Pharmacology, 1-17 (see here)
73. Perry, Warren, Damstra-Oddy, Storey, Francione, Annesley, Fisher, Müller-Taubenberger, & Williams (2020) A Dictyostelium discoideum mitochondrial fluorescent tagging vector that does not affect respiratory function. Biochemistry and Biophysics Reports (22), 100751, see here
72. Perry, Finch, Müller-Taubenberger, Leung, Warren, Damstra-Oddy, Sharma, Patra, Sarah Glyn, Boberska, Stewart, Baldwin, Piscitelli, Harvey, Harwood, Thompson, Claus, Greene, McNeish, Williams, Whalley, Williams (2019) A new mechanism for Cannabidiol in regulating the one-carbon cycle and methionine levels in Dictyostelium and in mammalian epilepsy models, British Journal of Pharmacology, 177, 4, DOI:10.1111/bph.14892 (see here)
71. Schaf, Damstra-Oddy & Williams (2019) Dictyostelium discoideum as a pharmacological model system to study the mechanisms of medicinal drugs and natural products. Int. J. Dev Biol. 63: 541 - 550 (see here)
70. Williams & Andrews (2019) Advice on avoiding the Valley of Death: Insights from a 3Rs model of aversive and emetic compound identification. ALTEX, 36(3), pp. 466-469, DOI:10.14573/altex.1810182 (see here)
69. Sharma, Otto, Warren, Beesley, King & Williams (2019) Gamma secretase orthologs are required for lysosomal activity and autophagic degradation in Dictyostelium discoideum, independent of PSEN (presenilin) proteolytic function, Autopahgy, 15(8):1407-1418 (see here)
68. Walker & Williams (2018) Medium Chain Fatty Acids, In Progress report on new antiepileptic drugs: A summary of the Fourteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XIV). II. Drugs in more advanced clinical development (Ed Bialer, Johannessen, Koepp, Levy, Perucca, Tomson and White). Epilepsia, In Press DOI: 10.1111/epi.14555 (see here)
67. Augustin, Williams, Cunningham, Devlin, Friedrich, Jayasekera, Hussain, Holliman, Mitchell, Jenkins, Chen†, Walker†*, Williams†* (2018) Synergistic AMPA receptor inhibition by Decanoic acid and Perampanel in Epilepsy Treatment, Epilepsia, In Press DOI: 10.1111/epi.14578 (see here)
66. Kelly, Sharma, Wilkinson, & Williams (2018) Diacylglycerol kinase (DGKA) regulates the effect of the epilepsy and bipolar disorder treatment valproic acid in Dictyostelium discoideum. Disease Models and Mechanisms. 11, dmm035600. doi:10.1242/dmm.03560 Ranked in the top 5% of all research outputs for this journal in the first month (see here)
65. Warren, Walker & Williams (2018) All you need is fats – for seizure control: using amoeba to advance epilepsy research. Frontiers in Cellular Neuroscience. 12: 199 (see here)
64. Cocorocchio, Baldwin, Stewart, Kim, Harwood, Thompson, Andrews & Williams (2017) Curcumin and derivatives function through protein phosphatase 2A and presenilin orthologues in Dictyostelium discoideum. Disease Models and Mechanisms. 29;11(1). pii: dmm032375. doi: 10.1242/dmm.032375 (see here)
63. Augustin, Khabbush, Williams, Eaton, Orford, Cross, Heales*, Walker*, Williams* (2018) Mechanisms of action of the medium chain triglyceride ketogenic diet in neurological and metabolic disorders, Lancet Neurology, 17 (1), 84–93(see here)
62. Williams & Bate (2017) Valproic acid and its congener propylisopropylacetic acid reduced the amount of soluble amyloid-beta oligomers released from 7PA2 cells. Neuropharmacology, 128, 54-62 PMID:28947378 (see here)
61. Marsh, Bagol, Williams, Dickson, Alifragis (2017) Synapsin I phosphorylation is dysregulated by beta-amyloid oligomers and restored by valproic acid. Neurobiol Dis.106:63-75. doi: 10.1016/j.nbd.2017.06.011. PMID: 28647556 (see here)
60. Frej, Otto and Williams (2017) Tipping the scales: lessons from simple model systems on inositol imbalance in neurological disorders. European Journal of Cell Biology; 96(2): 154-163. http://dx.doi.org/10.1016/j.ejcb.2017.01.007 PMID: 28153412 (see here)
59. Vauzour, Robles, Kergoat, Andres-Lacueva, Bánáti, Barberger-Gateau, Bowman, Caberlotto, Clarke, Hogervorst, Kiliaan, Lucca, Manach, Minihane, Mitchell Perneczky, Perry, Roussel, Schuermans, Sijben, Spencer, Thuret, van de Rest, Vandewoude, Wesnes, Williams, Williams, Ramirez (2016) Nutrition for the aging brain: towards evidence for an optimal diet.Ageing Research Reviews. pii: S1568-1637(16)30102-7. doi: 10.1016/j.arr.2016.09.010. (see here)
58. Otto, Sharma and Williams (2016) Non-Catalytic Roles of Presenilin throughout evolution. Journal of Alzheimer’s disease, 52(4):1177-87. DOI: 10.3233/JAD-150940 PMID: 27079701 (see here)
57. Walker and Williams (2016) Identifying the molecular mechanism of the MCT (ketogenic) diet. In ‘Ketogenic Diet and Metabolic Therapies: Expanded Roles in Health and Disease’, Oxford University Press edited by Susan Masino. ISBN: 9780190497996 (see here)
56. Frej, Clark, Le Roy, Lilla, Thomason, Otto, Churchill, Insall, Claus, Hawkins, Stephens and Williams (2016) The inositol-3-phosphate synthase biosynthetic enzyme has distinct catalytic and metabolic roles, Molecular and Cellular Biology, 36(10):1464-79 (see here)
55. Pistollato, Ohayon, Lam, Langley, Novak, Pamies, Perry, Trushina, Williams, Roher, Hartung, Harnad, Neal Barnard, Morris, Lai, Merkley,. Chandrasekera (2016) Alzheimer disease research in the 21st century: past and current failures, new perspectives and funding priorities. Oncotarget 7(26):38999-39016. doi: 10.18632/oncotarget.9175 (see here)
54. Cocorocchio, Ives, Clapham, Andrews, Williams (2016) Bitter tastant responses in the amoeba Dictyostelium correlate with rat and human taste assays. ALTEX, 33(3):225-36. doi: 10.14573/altex.1509011. PMID: 26708104 (see here)
53. Chang, Augustin, Boddum, Williams, Sun, Terschak, Hardege, Chen*, Walker*, Williams* (2016) Seizure control by decanoic acid through direct AMPA receptor inhibition. Brain, 139(Pt 2):431-43. PMID: 26608744 (see here)
52. Williams and Bate (2016) An in vitro model for synaptic loss in neurodegenerative diseases suggests a neuroprotective role for valproic acid via inhibition of cPLA2 dependent signalling, Neuropharmacology, 101:566-75 PMID: 26116815 (see here)
51. Otto*, Cocorocchio*, Munoz, Tyson, Bretschneider and Williams (2016) Employing Dictyostelium as an advantageous 3Rs model for pharmacogenetic research. In Methods in Molecular Biology: Chemotaxis, Eds Jin and Hereld, 1407, 123-130. DOI: 978-1-4939-3478-2. PMID: 27271898 (see here)
50. Zuckermann, La Ragione, Baines, and Williams (2015) Valproic acid protects against haemorrhagic shock-induced signalling changes via PPARγ activation in an in vitro model. British Journal of Pharmacology, 172(22):5306-17. PMID: 26333042 (see here)
51. Walker* and Williams* (2015) New experimental therapies for status epilepticus in pre-clinical development. Epilepsy and Behaviour. 49:290-3. PMID: 26189787 (see here)
48. Patel, Chuckowree, Coxhead, Guille, Wang, Zuckermann, Williams, Librizzi, Paranal, Bradner and Spencer (2014) Synthesis of hybrid anticancer agents based on kinase and histone deacetylase inhibitors. MedChemComm, 352(1):43-52. (see here)
47. Chang, Zuckermann, Williams, Close, Cano-Jaimez, McEvoy, Spencer, Walker† and Williams† (2014) Seizure control by derivatives of medium chain fatty acids associated with the ketogenic diet show novel branching-point structure for enhanced potency. Journal of Pharmacology and Experimental Therapeutics, 352(1):43-52. PMID: 25326131 (see here)
46. Cunliffe, Baines, Giachello, Lin, Morgan, Reuber, Russell, Walker and Williams (2014) Epilepsy Research Methods Update: Understanding the causes of epileptic seizures and identifying new treatments using non-mammalian model organisms Seizure, 24 44-51 doi: 10.1016/j.seizure.2014.09.018 PMID: 25457452 (see here)
45. Ludtmann, Otto, Schilde, Chen, Allan, Brace, Beesley, Kimmel, Fisher, Killick and Williams (2014) An ancestral non-proteolytic role for presenilin proteins in multicellular development of the social amoeba Dictyostelium discoideum. Journal of Cell Science. 127(7):1576-84. PMID: 24463814 (see here)
44. Chang, Walker† and Williams† (2013) Seizure-induced reduction in PIP3 levels contributes to seizure-activity and is rescued by valproic acid. Neurobiology of Disease. †Joint corresponding author. 62C:296-306 PMID: 24148856 (see here)
43. Waheed, Ludtmann, Pakes, Robery, Kuspa, Dinh, Baines*, Williams*† and Carew*† (2013) Naringenin inhibits the growth of Dictyostelium and MDCK-derived cysts in a polycystin-2 (TRPP2)-dependent manner. British Journal of Pharmacology.171(10):2659-70. *Joint last author. † joint corresponding author. PMID: 24116661 (see here)
42. Walker† and Williams† (2013) The search for better epilepsy treatments: from slime mould to coconuts. Biochem. Soc. Trans. 41(6):1625-8 PMID: 24256265 (see here)
41. Robery, Tyson, Dinh, Kuspa, Noegel, Bretschneider, Andrews, and Williams (2013) A novel human receptor involved in bitter tastant detection identified using the model organism Dictyostelium discoideum. Journal of Cell Science, 126(23):5465-76 PMID: 24006265 (see here)
40. Chang, Terbach, Plant, Chen, Walker† and Williams† (2013) Seizure control by ketogenic diet-associated medium chain fatty acids. Neuropharmacology, 69:105-14 PMID: 23177536 (see here)
39. Pakes, Veltman† and Williams† (2013) Zizimin and Dock guanine nucleotide exchange factors in cell function and disease. Small GTPases. 4 (1), 1-6 PMID: 23247359 (see here)
38. Pakes*, Veltman*, Rivero, Nasir, Insall and Williams (2012) The Rac GEF ZizB regulates development, cell motility and cytokinesis in Dictyostelium. J Cell Sci, 125, 10, 2457-65 PMID: 22366457
37. Elphick, Pawolleck, Guschina, Chaieb, Eikel, Nau, Harwood, Plant, and Williams (2012)Conserved valproic acid-induced lipid droplet formation in Dictyostelium and Human hepatocytes (huh7) identifies structurally active compounds. Disease Models and Mechanism, 5, 231-40 PMID: 22003123 (see here)
36. Chang, Orabi, Deranieh, Dham, Hoeller, Shimshoni, Yagen, Bialer, Greenberg, Walker and Williams (2012) The anti-epileptic valproic acid and other medium chain fatty acids acutely reduce phosphoinositide levels independently of inositol in Dictyostelium. Disease Models and Mechanism, 5, 115-124. FACULTY 1000 Selected, score 6 Recommended PMID: 21876211 (see here)
35. Riyahi, Frese, Steinert, Omosigho, Glöckner, Eichinger, Orabi, Williams and Noegel (2011) RpkA, a highly conserved GPCR with a lipid kinase domain, has a role in phagocytosis and anti-bacterial defense. Plos One, 6(11), e27311 PMID: 22073313 (see here)
34. Robery, Mukanowa, Nathalie Percie du Sert, Andrews and Williams (2011) Investigating the effect of emetic compounds on chemotaxis in Dictyostelium identifies a non-sentient model for bitter and hot tastant research. Plos One, 6(9), e24439 (see here)
33. Terbach, Shah, Keleman, Klein, Gordienko, Brown, Wilkinson, and Williams (2011) Identifying an uptake mechanism for the antiepileptic and bipolar disorder treatment valproic acid using the simple biomedical model Dictyostelium. J Cell Sci 124, 2267-76 PMID: 21652627 (see here)
32. Pakes, Jayasinghe and Williams (2011) Bio-electrospraying and aerodynamically assisted bio-jetting the model eukaryotic Dictyostelium discoideum: assessing stress and developmental competency post-treatment.Royal Society Interface Journal, 8, 1185-91 (see here)
31. Ludtmann, Boeckeler and Williams (2011) Molecular pharmacology in a simple model system: implicating MAP kinase and phosphoinositide signalling in bipolar disorder. Seminars in Cell and Developmental Biology, 22, 105-13 (see here)
30. King, Keim, Kapur, McQuillan, Ryves, Rogers, Teo, Dalton, Williams and Harwood (2010) Genetic Control of Lithium Sensitivity and Regulation of Inositol Biosynthetic Genes. Plos One, 5(6), e11151 (see here)
29. Chang, Chandler, Williams, Walker (2010) Inhibition of long-term potentiation by valproic acid through modulation of cyclic AMP. Epilepsia 51, 1533–1542 PMID: 20002144 (see here)
28. King, Teo, Ryves, Reddy, Peters, Orabi, Hoeller, Williams & Harwood (2009) The mood stabiliser lithium suppresses PIP3 signalling in Dictyostelium and human cells. Disease Models & Mechanisms, 2, 306-12 (see here)
27. Terbach and Williams (2009) Structure-function studies for the panacea, Valproic acid. Biochem Soc Trans, 37, 1126-32 (see here)
26. Williams (2009) Bipolar Disorder: Molecular and Cellular Biology. Employing multiple models, methods and mechanisms in bipolar disorder research. Biochemical Soc Trans. 37, 1077-9 (see here)
25. Teo, King, Dalton, Ryves, Williams & Harwood (2009) PI(3,4,5)P3 and inositol depletion as a cellular target of mood stabilizers. Biochem Soc Trans. 37, 1110-4
24. Pawolleck and Williams (2009) Quantifying in vivo phosphoinositide turnover in chemotactically-competent Dictyostelium cells. In Methods in Molecular Biology: Chemotaxis, Eds Jin and Hereld, 571, 283-90 (see here)
23. Xu, Müller-Taubenberger, Adley,Pawolleck, Lee, Sihra,Wiedemann, Maniak, Jin and Williams (2007)Attenuation of Phospholipid Signaling Provides a Novel Mechanism for the Action of Valproic Acid. Euk Cell, 6, 899-90PMID: 17435006 (see here)
22. Boeckeler and Williams (2007) Dictyostelium as a Biomedical Model. In: ENCYCLOPEDIA OF LIFE SCIENCES. John Wiley & Sons, Ltd: Chichester http://www.els.net/ [DOI: 10.1002/9780470015902.a0006038]
21. Shimshoni, Dalton, Eyal, Ewan, Jenkins, Williams, Yagen, Harwood, Bialer (2006) Probing CNS-active valproic acid analogues and amide derivatives for mood stabilizer properties. Mol Pharm, 71, 884-92
20. Boeckeler*, Adley*, Xu, Jenkins, Jin and Williams (2006) The neuroprotective agent, valproic acid, regulates the mitogen-activated protein kinase pathway through modulation of protein kinase A signalling in Dictyostelium discoideum. Eur J Cell Biol, 85, 1047-57
19. Williams, Boeckeler, Gräf, Müller-Taubenberger, Isberg, Wessels, Soll, Alexander & Alexander (2006) Towards a molecular understanding of human diseases using Dictyostelium discoideum. Trends in Mol Med, 12, 415-24
18. Adley, Keim and Williams (2006) Pharmacogenetics: Defining the genetic basis of drug action and inositol trisphosphate analysis. In Methods in Molecular Biology, Dictyostelium discoideum. Eds Eichinger and Rivero. Humana Press,507-516
17. Ryves, Dalton, Harwood and Williams (2005) GSK-3 activity in neocortical cells is inhibited by lithium but not carbamazepine or valproic acid. Bipolar Disorders 7, 260-4 PMID: 15898963
16. Eickholt, Towers, Ryves, Eikel, Adley, Ylinen, Chadborn, Harwood, Nau and Williams (2005) Effects of valproic acid derivatives on inositol trisphosphate depletion, teratogenicity, GSK-3b inhibition and viral replication - A screening approach for new bipolar disorder drugs based on the valproic acid core structure. Mol Pharm, 67,1-8 PMID:15687223
15. Williams (2005) Pharmacogenetics in model systems: defining a common mechanism of action for mood stabilizers. Prog in Neuro-Psychopharmacol and Biol Psychiatry 29, 1029-37
14. Williams and Harwood (2005) 3Li Lithium Metallotherapeutics. In Metallotherapeutic Drugs and Metal-Based Diagnostic Agents: The Use of Metals in Medicine. Eds Gielen and Tiekink. Wiley, 1-17
13. Breen, Harwood, Gregory, Sinclair, Collier, St. Clair and Williams (2004) Prolyl oligopeptidase and Z-prolinal-insensitive peptidase activity decrease in bipolar disorder not schizophrenia. Bipolar Disorders 6, 156-61. PMID:15005755
12. Keim, Williams and Harwood (2004) An inverse PCR technique to rapidly isolate the flanking DNA of Dictyostelium insertion mutants. Mol Biotechnol 26, 221-4
11. Williams (2004) Prolyl oligopeptidase and bipolar disorder in ‘Lithium and Mood Stabilizers: Mechanisms of Action’. Clin Neurosci Res 4, 233-42
10. Williams,Ryves, Dalton, Eickholt, Shaltiel, Agam and Harwood (2004) A molecular cell biology of lithium. Biochem Soc Trans 32, 799-802
9. Eickholt, Williams, and Harwood (2004) Mood stabilizers and the cell biology of neuronal growth cones in ‘Lithium and Mood Stabilizers: Mechanisms of Action’. Clin Neurosci Res 4, 189-99
8. Williams,Cheng, Mudge and Harwood (2002) A common mechanism of action for three mood-stabilizing drugs. Nature 417, 292-5 FACULTY 1000 Selected PMID:12015604
7. Coates, Grimson, Williams, Bergman, Blanton and Harwood(2002) Loss of the -catenin homologue aardvark causes ectopic stalk formation in Dictyostelium discoideum. Mech Devel 116, 117-27 FACULTY 1000 Selected, score 6 Recommended
6. Fraser, Young, Dajani, Franca-Koh, Ryves, Williams, Yeo, Webster, Richardson, Smalley, Pearl, Harwood and Dale (2002) Identification of the Axin and FRAT/GBP binding region of glycogen synthase kinase-3. J Biol Chem 277, 2176-85
5. Williams and Harwood (2000) Lithium therapy and signal transduction. Trends Pharmacol Sci 21, 61-4
4. Williams, Eames, Ryves, Viggars and Harwood (1999) Loss of a prolyl oligopeptidase confers resistance to lithium by elevation of inositol (1,4,5) trisphosphate. EMBO J 18, 2734-45
3. Calder, Williams, Ramaswamy, Rock, Campbell, Unkles, Kinghorn and Jackowski (1999) Cloning and Characterisation of a Eukaryotic Pantothenate Kinase Gene (panK) from Aspergillus nidulans. J Biol Chem 274, 2014-20
2. Williams,Davis and Howlett (1995) The nitrate and nitrite reductase-encoding genes of Leptosphaeria maculans are closely linked and transcribed in the same direction. Genetics 158, 153-4
1. Williams,Davis and Howlett (1994) Nitrate reductase of the ascomycetous fungus, Leptosphaeria maculans: Gene sequence and chromosomal location. Mol Gen Genet 244, 1-8
Other Recent publications
Otto and Williams, The Biochemist, 2014
Williams, The Biologist May 2013
Williams, The Conversation May 2013
Williams, Higher magazine May 2013
Front Covers
1. Nature (see research articles #8 above)
2. Prog in Neuro-Psychopharmacol and Biol Psychiatry 2006, 30, 1 (see research articles #15 above)
3. J R Soc Interface, 2011, 8(61):1185-91 (see research articles #33 above)
Recent Press Coverage
Press release. 16/10/2018.Improving the control of epilepsy by combining a diet and a drug.
Press release 21/8/2018. A new breakthrough proposes a link between epilepsy and bipolar disorder. Covered by over 62 sites, including the Daily Mail and the ITN website, ITV, The Evening Telegraph AlphaGalileo, Express and Star, plus a range of regional media including local perss (Surrey Comet, Review St Albans and Harpenden, Hillingdon and Uxbridge Times) etc
Talk Science 13/10/2016. https://www.bl.uk/events/replace-reduce-refine-animals-in-research/
Press release 25/11/2015. Covered by over 22 news agents worldwide, including an article in New Scientist, with parallel releases from the funding body and UCL.
Press release 1/9/2015 Diabetes drug provide new treatment for death by massive blood loss, repeated over 10 different news networks worldwide
BBC news (BBC4 North, 12/11/2013) and nationally (13/11/2013 breakfast news, 13.30 and 22.25pm)
and Newsnight (Broadcast nationally 13/5/2014) Research coverage and 3Rs comment
Press release: Important breakthrough in identifying effect of epilepsy treatment, repeated over 15 different news networks worldwide
Press release, Component of citrus fruits found to block the formation of kidney cysts. Covered in 20 sites worldwide, including medicalxpress, biochemist, netdoctor, australiasianscience, healthcanal, dnaindia, innews, fr.news
Press release, Discovery offers new treatment for epilepsy, 21 Nov 2012 covered in19 different news outlets worldwide including bbc.co.uk/news/health and BBC News online
Newspaper article: Pioneering work of Egham Scientists. Egham and Staines News, 11 Oct 2012
Press release by UFAW: New research looks to reduce animal testing for drug development, 8 Oct 2012
Press release, New research looks to reduce animal testing for drug development http://www.rhul.ac.uk/aboutus/newsandevents/news/newsarticles/newresearchlookstoreduceanimaltestingfordrugdevelopment.aspx 9/10/2012
Press release, Royal Holloway Leads the Way on Replacing Animals to Research Bipolar Disorder: RHUL press office 20/5/2012
Global Medical Discoveries announcement (http://globalmedicaldiscovery.com).
Press release: Novel epilepsy treatment could reduce risk of birth defects. RHUL and UCL press office 30/8/2011
Radio Interview: Deutschlandfunk, "Forschung aktuell" Sept 2009 http://www.dradio.de/dlf/sendungen/forschak/1026124/
Press release: Amoeba used to reduce animals used in epilepsy research. July 2009 http://www.rhul.ac.uk/messages/press/message.asp?ref_no=1998
Recent Outreach
New Scientist live, ExCel, London October 2017, see here
Higher Magazine article Dec 2015
Pridham lecture: (High School students) Nov 2015
Science Museum Exhibition, 20 Feb 2015. Exhibition to the public regarding Dictyostelium as a non-animal model for research. Attended by over 300 people, 99% who rated it as ‘excellent’ or related.
Mysteries of the Unseen World, a film in 3D by National Geographic. We provided access for filming and cells to image for this movie. Released Oct 2014.
Epilepsy research without using animals, see here
Recent Invited Conference Papers/Seminars
International
National
In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This person’s work contributes towards the following SDG(s):
Research output: Contribution to journal › Article › peer-review
Research output: Chapter in Book/Report/Conference proceeding › Chapter
Research output: Contribution to journal › Article › peer-review
Research output: Contribution to journal › Article › peer-review
Research output: Contribution to journal › Article › peer-review
2/08/16 → 1/02/20
Project: Other