Early in his research career, Emeritus Professor Warren Tate discovered translational frameshifting as a new mechanism of gene regulation which led to a study of the mechanism as a potential drug target for HIV-1.
Emeritus Professor Tate’s laboratory has had a long-term interest in protein synthesis and in particular, the decoding and recoding mechanisms on the ribosome at stop signals. Thirty years ago, a chance discovery of recoding called frameshifting (a cellular mechanism for regulating gene expression during protein synthesis) spurred an interest in the frameshift mechanism of HIV-1 as a potential site of vulnerability in the virus. Now they have focused on the only gene in the animal kingdom known to use this mechanism, human gene PEG10. Significantly, PEG10 uses the same frameshifting expression strategy as HIV-1 to produce two proteins.
In addition to his fundamental molecular biology research, Emeritus Professor Tate has been involved in a completely different research area: molecular neurobiology. With his Otago colleagues Professor Cliff Abraham and Dr Joanna Williams, he is looking at the mechanisms of neurological diseases. His research into the molecular basis of memory has progressed to the development of a brain protein fragment that can restore memory and has potential as a therapeutic agent for Alzheimer's disease. They believe this external secreted protein is a signalling molecule that can switch on a signalling pathway and activate a range of gene responses to protect and enhance memory; an activity that may be critical as a counterbalance in the development of Alzheimer’s disease. They have developed a simple recombinant production and purification process for this brain protein, secreted amyloid precursor protein-alpha, a neuroprotective protein that shows a lower concentration in Alzheimer’s patients. Remarkably, their recombinant protein alone can restore memory to rats impaired by drug treatment, not only in their electrophysiological responses but also in trials to determine memory of learned spatial tasks.
In 2010, Emeritus Professor Warren Tate was awarded New Zealand’s premier science and technology honour, the 2010 Rutherford Medal. He is a Fellow of the Royal Society of New Zealand and of the New Zealand Institute of Chemistry. He has been a Fellow of the Alexander von Humboldt Foundation of Germany, and an International Research Scholar of the Howard Hughes Medical Institute of the United States.
Watch Emeritus Professor Warren Tate's 2020 BHRC Lecture on ME/CFS
Find out more about Emeritus Professor Warren Tate’s research
Publications
Lam, P., Vinnakota, C., Calvo-Flores Guzmán, B., Newland, J., Peppercorn, K., Tate, W. P., … Kwakowsky, A. (2022). Beta-amyloid (Aβ1-42) increases the expression of NKCC1 in the mouse hippocampus. Molecules, 27, 2440. doi: 10.3390/molecules27082440
Guévremont, D., Tsui, H., Knight, R. G., Fowler, C. J., Masters, C. L., Martins, R. N., Abraham, W. C., Tate, W. P., Cutfield, N. J., & Williams, J. M. (2022). Plasma microRNA vary in association with the progression of Alzheimer's disease. Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring, 14, e12251. doi: 10.1002/dad2.12251
Ohline, S. M., Chan, C., Schoderboeck, L., Wicky, H. E., Tate, W. P., Hughes, S. M., & Abraham, W. C. (2022). Effect of soluble amyloid precursor protein-alpha on adult hippocampal neurogenesis in a mouse model of Alzheimer's disease. Molecular Brain, 15, 5. doi: 10.1186/s13041-021-00889-1
Tate, W. (2021). The three macromolecules in the Central Dogma brought alive by over 60 years of biochemical and molecular studies assisted by visualisation and 'omic' technologies. Proceedings of the 16th Congress of the Federation of Asian & Oceanic Biochemists & Molecular Biologists (FAOBMB). (pp. 160). Retrieved from https://www.faobmb2021.org
Bernhardt, H. S., & Tate, W. P. (2021). A new perspective on the Maillard reaction and the origin of life. Journal of Molecular Evolution. Advance online publication. doi: 10.1007/s00239-021-10030-4
Poole, E. S., Major, L. L., Cridge, A. G., & Tate, W. P. (2004). The mechanism of recoding in pro- and eukaryotes. In K. H. Nierhaus & D. N. Wilson (Eds.), Protein synthesis and ribosome structure: Translating the genome. (pp. 397-428). Weinheim, Germany: Wiley-VCH.
Chapter in Book - Research
Tate, W. P., Dalphin, M. E., Pel, H. J., & Mannering, S. A. (1996). Decoding efficiencies of translational stop signals: a new facet of cellular regulation. In J. K. Setlow (Ed.), Genetic Engineering, Principles and Methods, Volume 18. (pp. 157-182). New York: Plenum Press.
Chapter in Book - Research
Tate, W. P., & Marshall, C. J. (2018). Post-dormancy transcription and translation in the brine shrimp. In R. A. Browne, P. Sorgeloos & C. N. A. Trotman (Eds.), Artemia biology. (pp. 21-36). Boca Raton, FL: Taylor & Francis. doi: 10.1201/9781351069892
Chapter in Book - Other
Guévremont, D., Tsui, H., Knight, R. G., Fowler, C. J., Masters, C. L., Martins, R. N., Abraham, W. C., Tate, W. P., Cutfield, N. J., & Williams, J. M. (2022). Plasma microRNA vary in association with the progression of Alzheimer's disease. Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring, 14, e12251. doi: 10.1002/dad2.12251
Journal - Research Article
Lam, P., Vinnakota, C., Calvo-Flores Guzmán, B., Newland, J., Peppercorn, K., Tate, W. P., … Kwakowsky, A. (2022). Beta-amyloid (Aβ1-42) increases the expression of NKCC1 in the mouse hippocampus. Molecules, 27, 2440. doi: 10.3390/molecules27082440
Journal - Research Article
Ohline, S. M., Chan, C., Schoderboeck, L., Wicky, H. E., Tate, W. P., Hughes, S. M., & Abraham, W. C. (2022). Effect of soluble amyloid precursor protein-alpha on adult hippocampal neurogenesis in a mouse model of Alzheimer's disease. Molecular Brain, 15, 5. doi: 10.1186/s13041-021-00889-1
Journal - Research Article
Livingstone, R. W., Elder, M. K., Singh, A., Westlake, C. M., Tate, W. P., Abraham, W. C., & Williams, J. M. (2021). Secreted amyloid precursor protein-alpha enhances LTP through the synthesis and trafficking of Ca2+-permeable AMPA receptors. Frontiers in Molecular Neuroscience, 14, 660208. doi: 10.3389/fnmol.2021.660208
Journal - Research Article
Ryan, M., Tan, V. T. Y., Thompson, N., Guévremont, D., Mockett, B. G., Tate, W. P., Abraham, W. C., Hughes, S. M., & Williams, J. (2021). Lentivirus-mediated expression of human secreted amyloid precursor protein-alpha promotes long-term induction of neuroprotective genes and pathways in a mouse model of Alzheimer’s disease. Journal of Alzheimer's Disease, 79, 1075-1090. doi: 10.3233/JAD-200757
Journal - Research Article
Calvo-Flores Guzmán, B., Chaffey, T. E., Palpagama, T. H., Waters, S., Boix, J., Tate, W. P., Peppercorn, K., … Kwakowsky, A. (2020). The interplay between beta-amyloid 1-42 (Aβ1-42)-induced hippocampal inflammatory response, p-tau, vascular pathology, and their synergistic contributions to neuronal death and behavioral deficits. Frontiers in Molecular Neuroscience, 13, 522073. doi: 10.3389/fnmol.2020.552073
Journal - Research Article
Helliwell, A. M., Sweetman, E. C., Stockwell, P. A., Edgar, C. D., Chatterjee, A., & Tate, W. P. (2020). Changes in DNA methylation profiles of myalgic encephalomyelitis/chronic fatigue syndrome patients reflect systemic dysfunctions. Clinical Epigenetics, 12(1), 167. doi: 10.1186/s13148-020-00960-z
Journal - Research Article
Sweetman, E., Kleffmann, T., Edgar, C., de Lange, M., Vallings, R., & Tate, W. (2020). A SWATH-MS analysis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome peripheral blood mononuclear cell proteomes reveals mitochondrial dysfunction. Journal of Translational Medicine, 18, 365. doi: 10.1186/s12967-020-02533-3
Journal - Research Article
Vinnakota, C., Govindpani, K., Tate, W. P., Peppercorn, K., Anekal, P. V., Waldvogel, H. J., … Kwakowsky, A. (2020). An α5 GABAA receptor inverse agonist, α5IA, attenuates amyloid beta-induced neuronal death in mouse hippocampal cultures. International Journal of Molecular Sciences, 21(9), 3284. doi: 10.3390/ijms21093284
Journal - Research Article
Yeung, J. H. Y., Calvo-Flores Guzmán, B., Palpagama, H. T., Ethiraj, J., Zhai, Y., Tate, W. P., Peppercorn, K., … Kwakowsky, A. (2020). Amyloid-beta1-42 induced glutamatergic receptor and transporter expression changes in the mouse hippocampus. Journal of Neurochemistry, 155, 62-80. doi: 10.1111/jnc.15099
Journal - Research Article
Yeung, J. H. Y., Palpagama, T. H., Tate, W. P., Peppercorn, K., Waldvogel, H. J., Faull, R. L. M., & Kwakowsky, A. (2020). The acute effects of amyloid-Beta1–42 on glutamatergic receptor and transporter expression in the mouse hippocampus. Frontiers in Neuroscience, 13, 1427. doi: 10.3389/fnins.2019.01427
Journal - Research Article
Livingstone, R. W., Elder, M. K., Barrett, M. C., Westlake, C. M., Peppercorn, K., Tate, W. P., Abraham, W. C., & Williams, J. M. (2019). Secreted amyloid precursor protein-alpha promotes arc protein synthesis in hippocampal neurons. Frontiers in Molecular Neuroscience, 12, 198. doi: 10.3389/fnmol.2019.00198
Journal - Research Article
Mockett, B. G., Guévremont, D., Elder, M. K., Parfitt, K. D., Peppercorn, K., Morrissey, J., Singh, A., Hintz, T. J., … Tate, W. P., Williams, J. M., & Abraham, W. C. (2019). Glutamate receptor trafficking and protein synthesis mediate the facilitation of LTP by secreted amyloid precursor protein-alpha. Journal of Neuroscience, 39(17), 3188-3203. doi: 10.1523/jneurosci.1826-18.2019
Journal - Research Article
Morrissey, J. A., Bigus, E., Necarsulmer, J. C., Srinivasan, V., Peppercorn, K., O'Leary, D. J., Mockett, B. G., Tate, W. P., Hughes, S. M., … Abraham, W. C. (2019). The tripeptide RER mimics secreted amyloid precursor protein-alpha in upregulating LTP. Frontiers in Cellular Neuroscience, 13, 459. doi: 10.3389/fncel.2019.00459
Journal - Research Article
Morrissey, J. A., Mockett, B. G., Singh, A., Kweon, D., Ohline, S. M., Tate, W. P., Hughes, S. M., & Abraham, W. C. (2019). A C-terminal peptide from secreted amyloid precursor protein-α enhances long-term potentiation in rats and a transgenic mouse model of Alzheimer's disease. Neuropharmacology, 157, 107670. doi: 10.1016/j.neuropharm.2019.107670
Journal - Research Article
Sweetman, E., Ryan, M., Edgar, C., MacKay, A., Vallings, R., & Tate, W. (2019). Changes in the transcriptome of circulating immune cells of a New Zealand cohort with myalgic encephalomyelitis/chronic fatigue syndrome. International Journal of Immunopathology & Pharmacology, 33, 1-8. doi: 10.1177/2058738418820402
Journal - Research Article
Cridge, A. G., Crowe-McAuliffe, C., Mathew, S. F., & Tate, W. P. (2018). Eukaryotic translational termination efficiency is influenced by the 3' nucleotides within the ribosomal mRNA channel. Nucleic Acids Research, gkx1315. doi: 10.1093/nar/gkx1315
Journal - Research Article
Mackay, A., & Tate, W. P. (2018). A compromised paraventricular nucleus within a dysfunctional hypothalamus: A novel neuroinflammatory paradigm for ME/CFS. International Journal of Immunopathology & Pharmacology, 32, 1-8. doi: 10.1177/2058738418812342
Journal - Research Article
Tan, V. T. Y., Mockett, B. G., Ohline, S. M., Parfitt, K. D., Wicky, H. E., Peppercorn, K., Schoderboeck, L., Yahaya, M. F. b., Tate, W. P., Hughes, S. M., & Abraham, W. C. (2018). Lentivirus-mediated expression of human secreted amyloid precursor protein-alpha prevents development of memory and plasticity deficits in a mouse model of Alzheimer's disease. Molecular Brain, 11, 7. doi: 10.1186/s13041-018-0348-9
Journal - Research Article
Xiong, M., Jones, O. D., Peppercorn, K., Ohline, S. M., Tate, W. P., & Abraham, W. C. (2017). Secreted amyloid precursor protein-alpha can restore novel object location memory and hippocampal LTP in aged rats. Neurobiology of Learning & Memory, 138, 291-299. doi: 10.1016/j.nlm.2016.08.002
Journal - Research Article
Kwakowsky, A., Potapov, K., Kim, S., Peppercorn, K., Tate, W. P., & Ábrahám, I. M. (2016). Treatment of beta amyloid 1-42 (Αβ1-42)-induced basal forebrain cholinergic damage by a non-classical estrogen signaling activator in vivo. Scientific Reports, 6, 21101. doi: 10.1038/srep21101
Journal - Research Article
Cardno, T. S., Shimaki, Y., Sleebs, B. E., Lackovic, K., Parisot, J. P., Moss, R. M., Crowe-McAuliffe, C., Mathew, S. F., Edgar, C. D., Kleffmann, T., & Tate, W. P. (2015). HIV-1 and human PEG10 frameshift elements are functionally distinct and distinguished by novel small molecule modulators. PLoS ONE, 10(10), e0139036. doi: 10.1371/journal.pone.0139036
Journal - Research Article
Mathew, S. F., Crowe-McAuliffe, C., Graves, R., Cardno, T. S., McKinney, C., Poole, E. S., & Tate, W. P. (2015). The highly conserved codon following the Slippery Sequence Supports -1 frameshift efficiency at the HIV-1 frameshift site. PLoS ONE, 10(3), e0122176. doi: 10.1371/journal.pone.0122176
Journal - Research Article
Ramsay, J. P., Tester, L. G. L., Major, A. S., Sullivan, J. T., Edgar, C. D., Kleffmann, T., … Tate, W. P., … Ronson, C. W. (2015). Ribosomal frameshifting and dual-target antiactivation restrict quorum-sensing–activated transfer of a mobile genetic element. PNAS, 112(3), 4104-4109. doi: 10.1073/pnas.1501574112
Journal - Research Article
Imhoff, F. M., Yang, D., Mathew, S. F., Clarkson, A. N., Kawagishi, Y., Tate, W. P., Koishi, K., & McLennan, I. S. (2013). The type 2 anti-Müllerian hormone receptor has splice variants that are dominant-negative inhibitors. FEBS Letters, 587(12), 1749-1753. doi: 10.1016/j.febslet.2013.04.014
Journal - Research Article
Ryan, M. M., Morris, G. P., Mockett, B. G., Bourne, K., Abraham, W. C., Tate, W. P., & Williams, J. M. (2013). Time-dependent changes in gene expression induced by secreted amyloid precursor protein-alpha in the rat hippocampus. BMC Genomics, 14, 376. doi: 10.1186/1471-2164-14-376
Journal - Research Article
Baratchi, S., Evans, J., Tate, W. P., Abraham, W. C., & Connor, B. (2012). Secreted amyloid precursor proteins promote proliferation and glial differentiation of adult hippocampal neural progenitor cells. Hippocampus, 22(7), 1517-1527. doi: 10.1002/hipo.20988
Journal - Research Article
Bernhardt, H. S., & Tate, W. P. (2012). Primordial soup or vinaigrette: Did the RNA world evolve at acidic pH? Biology Direct, 7(4). doi: 10.1186/1745-6150-7-4
Journal - Research Article
Ryan, M. M., Ryan, B., Kyrke-Smith, M., Logan, B., Tate, W. P., Abraham, W. C., & Williams, J. M. (2012). Temporal profiling of gene networks associated with the late phase of long-term potentiation in vivo. PLoS ONE, 7(7), e40538. doi: 10.1371/journal.pone.0040538
Journal - Research Article
Morgan, N. V., Goddard, S., Cardno, T. S., McDonald, D., Rahman, F., Barge, D., Ciupek, A., … Tate, W. P., … Maher, E. R. (2011). Mutation in the TCRα subunit constant gene (TRAC) leads to a human immunodeficiency disorder characterized by a lack of TCRαβ+ T cells. Journal of Clinical Investigation, 121(2), 695-702. doi: 10.1172/JCI41931
Journal - Research Article
Ryan, M. M., Mason-Parker, S. E., Tate, W. P., Abraham, W. C., & Williams, J. M. (2011). Rapidly induced gene networks following induction of long-term potentiation at perforant path synapses in vivo. Hippocampus, 21(5), 541-553. doi: 10.1002/hipo.20770
Journal - Research Article
Bernhardt, H. S., & Tate, W. P. (2010). The transition from noncoded to coded protein synthesis: Did coding mRNAs arise from stability-enhancing binding partners to tRNA? Biology Direct, 5, 16. doi: 10.1186/1745-6150-5-16
Journal - Research Article
Young, D. J., Edgar, C. D., Murphy, J., Fredebohm, J., Poole, E. S., & Tate, W. P. (2010). Bioinformatic, structural, and functional analyses support release factor-like MTRF1 as a protein able to decode nonstandard stop codons beginning with adenine in vertebrate mitochondria. RNA, 16(6), 1146-1155. doi: 10.1261/rna.1970310
Journal - Research Article
Young, D. J., Edgar, C. D., Poole, E. S., & Tate, W. P. (2010). The codon specificity of eubacterial release factors is determined by the sequence and size of the recognition loop. RNA, 16, 1623-1633. doi: 10.1261/rna.2117010
Journal - Research Article
Cardno, T. S., Poole, E. S., Mathew, S. F., Graves, R., & Tate, W. P. (2009). A homogeneous cell-based bicistronic fluorescence assay for high-throughput identification of drugs that perturb viral gene recoding and read-through of nonsense stop codons. RNA, 15(8), 1614-1621. doi: 10.1261/rna.1586709
Journal - Research Article
Claasen, A. M., Guévremont, D., Mason-Parker, S. E., Bourne, K., Tate, W. P., Abraham, W. C., & Williams, J. M. (2009). Secreted amyloid precursor protein-α upregulates synaptic protein synthesis by a protein kinase G-dependent mechanism. Neuroscience Letters, 460, 92-96. doi: 10.1016/j.neulet.2009.05.040
Journal - Research Article
Jacobs, G. H., Chen, A., Stevens, S. G., Stockwell, P. A., Black, M. A., Tate, W. P., & Brown, C. M. (2009). Transterm: A database to aid the analysis of regulatory sequences in mRNAs. Nucleic Acids Research, 37(Database issue), D72-D76. doi: 10.1093/nar/gkn763
Journal - Research Article
Bernhardt, H. S., & Tate, W. P. (2008). Evidence from glycine transfer RNA of a frozen accident at the dawn of the genetic code. Biology Direct, 3, 53. doi: 10.1186/1745-6150-3-53
Journal - Research Article
Bernhardt, H. S., & Tate, W. P. (2008). Self-assembling transfer RNA has potential for nanoparticle arrays. Current Applied Physics, 8(3-4), 380-382. doi: 10.1016/j.cap.2007.10.035
Journal - Research Article
Taylor, C. J., Ireland, D. R., Ballagh, I., Bourne, K., Marechal, N. M., Turner, P. R., Bilkey, D. K., Tate, W. P., & Abraham, W. C. (2008). Endogenous secreted amyloid precursor protein-α regulates hippocampal NMDA receptor function, long-term potentiation and spatial memory. Neurobiology of Disease, 31(2), 250-260. doi: 10.1016/j.nbd.2008.04.011
Journal - Research Article
Clark, M. B., Jänicke, M., Gottesbühren, U., Kleffmann, T., Legge, M., Poole, E. S., & Tate, W. P. (2007). A mammalian gene PEG10 expresses two reading frames by high efficiency -1 frameshifting in embryonic-associated tissues. Journal of Biological Chemistry, 282(52), 37359-37369.
Journal - Research Article
Poole, E. S., Young, D. J., Askarian-Amiri, M. E., Scarlett, D.-J. G., & Tate, W. P. (2007). Accommodating the bacterial decoding release factor as an alien protein among the RNAs at the active site of the ribosome. Cell Research, 17, 591-607.
Journal - Research Article
Soleimanpour-Lichaei, H. R., Kühl, I., Gaisne, M., Passos, J. F., Wydro, M., Rorbach, J., … Tate, W., … Chrzanowska-Lightowlers, Z. (2007). mtRF1a is a human mitochondrial translation release factor decoding the major termination codons UAA and UAG. Molecular Cell, 27, 745-757.
Journal - Research Article
Turner, P. R., Bourne, K., Garama, D., Carne, A., Abraham, W. C., & Tate, W. P. (2007). Production, purification and functional validation of human secreted amyloid precursor proteins for use as neuropharmacological reagents. Journal of Neuroscience Methods, 164, 68-74.
Journal - Research Article
Williams, J. M., Guévremont, D., Mason-Parker, S. E., Luxmanan, C., Tate, W. P., & Abraham, W. C. (2007). Differential trafficking of AMPA and NMDA receptors during long-term potentiation in awake adult animals. Journal of Neuroscience, 27(51), 14171-14178.
Journal - Research Article
Cridge, A. G., Major, L. L., Mahagaonkar, A. A., Poole, E. S., Isaksson, L. A., & Tate, W. P. (2006). Comparison of characteristics and function of translation termination signals between and within prokaryotic and eukaryotic organisms. Nucleic Acids Research, 34(7), 1959-1973. doi: 10.1093/nar/gkl074
Journal - Research Article
Jacobs, G. H., Stockwell, P. A., Tate, W. P., & Brown, C. M. (2006). Transterm: Extended search facilities and improved integration with other databases. Nucleic Acids Research, 34(Database), D37-D40.
Journal - Research Article