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
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
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
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
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
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
Chapter in Book - Research
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.
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 - Other
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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.
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.
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.
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.
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.
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
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.
Tate, W. P., & Poole, E. S. (2004). The ribosome: Lifting the veil from a fascinating organelle. BioEssays, 26, 582-588.
Mockett, B. G., Brooks, W. M., Tate, W. P., & Abraham, W. C. (2004). Dopamine D1/D5 receptor activation fails to initiate an activity-independent late-phase LTP in rat hippocampus. Brain Research, 1021, 92-100.
Turner, P. R., O'Connor, K., Tate, W. P., & Abraham, W. C. (2003). Roles of amyloid precursor protein and its fragments in regulating neural activity, plasticity and memory. Progress in Neurobiology, 70, 1-32.
Williams, J. M., Guévremont, D., Kennard, J. T. T., Mason-Parker, S. E., Tate, W. P., & Abraham, W. C. (2003). Long-term regulation of N-methyl-D-aspartate receptor subunits and associated synaptic proteins following hippocampal synaptic plasticity. Neuroscience, 118, 1003-1013.
Cridge, A. G., Poole, E. S., & Tate, W. P. (2003). The signal for stop in protein synthesis in eukaryotes: Evidence for a sequence element rather than a simple stop codon. New Zealand BioScience, 12, 37-38.
Scarlett, D.-J. G., McCaughan, K. K., Wilson, D. N., & Tate, W. P. (2003). Mapping functionally important motifs SPF and GGQ of the decoding release factor RF2 to the Escherichia coli ribosome by hydroxyl radical footprinting. Journal of Biological Chemistry, 278(17), 15095-15104.
