Red X iconGreen tick iconYellow tick icon

Contact Details

Email
warren.tate@otago.ac.nz
Position
Professor
Department
Department of Biochemistry
Qualifications
MSc (Well) PhD (Otago) FNZIC FRSNZ MA-PIMBN
Research summary
Protein synthesis, genetic recoding, memory mechanisms, infectious disease

Research

My laboratory has had a long-term interest in understanding protein synthesis and, in particular, decoding and recoding mechanisms on the ribosome at stop signals. Important recent investigations have focused on how the decoding release factor as a molecular mimic of tRNA recognises the individual bases of the stop signal, and how alternative genetic codes like those found in vertebrate mitochondria can be accommodated into an integrated model. This has been helped considerably by the 2008 atomic resolution structures of the ribosome:factor complex.


The decoding release factor interacting with stop codon UAG.

From our chance discovery in the 1980s of recoding (frameshifting; a cellular mechanism for regulating gene expression during protein synthesis), we developed an interest in the frameshift mechanism of HIV-1 as a potential site of vulnerability in the virus. Now, our interest has extended to the only gene in the animal kingdom known to use this mechanism, human gene PEG10. The gene was relatively recently acquired as a retroelement insertion and has undergone molecular domestication to become expressed in placenta and amniotic membranes but not, as we have shown, in adult tissues. Significantly, it uses the same frameshifting expression strategy as HIV-1 to produce two proteins.


Morris water maze: testing memory in a rat.

A second long-standing interest has been the molecular mechanisms of mammalian memory and how they are impaired in human neurological diseases, particularly Alzheimer's. These investigations have focused on the molecular changes in neurons of the hippocampus when they receive electrical signals within in vivo models and more recently included behavioural studies. We have developed a simple recombinant production and purification strategy for a processed brain protein, secreted amyloid precursor protein-alpha, a protein that is neuroprotective but whose concentration is lowered in Alzheimer's patients. Remarkably, we have shown our 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. We 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

Publications

Peppercorn, K., Edgar, C. D., Kleffmann, T., & Tate, W. P. (2023). A pilot study on the immune cell proteome of long COVID patients shows changes to physiological pathways similar to those in myalgic encephalomyelitis/chronic fatigue syndrome. Scientific Reports, 13(1), 22068. doi: 10.1038/s41598-023-49402-9 Journal - Research Article

Stokes, C., Basak, I., Tate, W., & Hughes, S. (2023). Identifying superheroes in neurodegenerative disease. Proceedings of the Genetics Otago (GO) Annual Symposium & Workshops. Retrieved from https://blogs.otago.ac.nz/go Conference Contribution - Published proceedings: Abstract

Walker, M. O. M., Peppercorn, K., Kleffmann, T., Edgar, C. D., & Tate, W. P. (2023). An understanding of the immune dysfunction in susceptible people who develop the post-viral fatigue syndromes Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID. Medical Research Archives, 11(7). doi: 10.18103/mra.v11i7.1.4083 Journal - Research Article

Peppercorn, K., Kleffmann, T., Hughes, S. M., & Tate, W. P. (2023). Secreted amyloid precursor protein alpha (sAPPα) regulates the cellular proteome and secretome of mouse primary astrocytes. International Journal of Molecular Sciences, 24, 7165. doi: 10.3390/ijms24087165 Journal - Research Article

Tate, W. P., Walker, M. O. M., Peppercorn, K., Blair, A. L. H., & Edgar, C. D. (2023). Towards a better understanding of the complexities of myalgic encephalomyelitis/chronic fatigue syndrome and long COVID [Review]. International Journal of Molecular Sciences, 24(6), 5124. doi: 10.3390/ijms24065124 Journal - Research Article

Back to top