Ted Allison
PhD: Biology, University of Victoria, BC
- Post-doctoral training: University of Michigan, Ann Arbor MI
- Position: Associate Professor
Department of Biological Sciences Centre for Prions and Protein Folding Diseases Neuroscience and Mental Health Institute Faculty of Science
Email: ted.allison@ualberta.ca
Lab webpage:
Background
Zebrafish Models of Alzheimer & Prion Disease. We are creating transgenic and mutant zebrafish toward the goal of modeling disease progression. We seek tractable disease models, or at least in vivo assays of protein function, to enable screening of candidate genes or small molecules as putative therapeutics. We have a goal of creating prion-infectible fish. A second approach is to explore genetic interactions and familial disease mutations. To complete these objectives we have improved upon and successfully deployed zinc finger nucleases, TALENS and CRISPR allowing targeted knockout of genes-of-interest. We also have created a variety of topical transgenic fish. We will continue to assess how these genetic manipulations affect how disease spreads through the CNS and affect synaptogenesis, including through collaborative in vivo electrophysiology approaches.Current Research
PrP as APP interactor
The APP holoprotein is cleaved to give rise to Aβ, the toxic protein that aggregates into oligomers and plaques associated with neuron death in Alzheimer Disease. It is now accepted that PrP C is a receptor for Aβ; We have expanded this research space by showing that PrP C is also an interactor with the APP holoprotein. The interaction occurs at the level of biochemistry and synergistic toxic knockdown when APP and PrP C are knocked down in zebrafish. Further investigations will dissect this interaction.
Prion-like diseases + loss-of-function
We assert that loss of protein function during misfolding, e.g. for APP and PrP C, contributes substantially to the etiology of neurodegeneration. Disruption of APP or PrP C levels/functions are promising therapeutic routes to treat Alzheimer disease. Thus we seek to fill a vast knowledge gap regarding the normal roles of APP and PrP C as they pertain to Alzheimer Disease. Zebrafish provide a compelling platform for such studies because knockout of these proteins reveals highly tractable and relevant phenotypes (e.g. seizure susceptibility, excitotoxicity, sleep disorders) while their genetic pliability enables dissection of the molecular components behind the phenotypes.
Conserved functions of PrP C
We have demonstrated that mammalian PrP C can rescue phenotypes in knockout zebrafish, demonstrating deeply conserved (important!) functions in cell adhesion and modulation of neural excitability. We will characterize purposefully engineered APP and PrP mutant zebrafish in vivo via a cutting-edge fluorescence reporter system that quantifies neural activity; this will test PrP C and APP requirements for seizures, hyperexcitability, and excitotoxicity, and enable mapping of which neurons and brain centres mediate such dysfunction with unprecedented specificity.
Drug screens
We will deploy our engineered zebrafish into high-throughput drug screening platforms. The zebrafish allows compelling in vivo drug screens that permit unprecedented detection of lead compounds (that would be missed in simpler systems) because the immense complexity of CNS cell physiology is well represented and because metabolism of drugs by diverse differentiated cell types is often required for the drug's action.
Selected publications
Locskai LF1, T Gill1, SAW Tan, AH Burton, H Alyenbaawi, EA Burton, WT Allison. 2025. A larval zebrafish model of traumatic brain injury: Optimizing the dose of neurotrauma for discovery of treatments and aetiology. Biology Open. 14 (2): bio060601. 1co-first authors. doi: 10.1242/bio.060601.
Locskai LF, H Alyenbaawi, WT Allison. 2024. Antiepileptic Drugs as potential Dementia Prophylactics following Traumatic Brain Injury. Invited Review. Annual Review of Pharmacology and Toxicology. Volume 64: 577-598.
doi: 10.1146/annurev-pharmtox-
Pokrishevsky E1, MG DuVal1, L McAlary, S Louada, S Pozzi, A Roman, SS Plotkin, A Dijkstra, JP Julien, WT Allison*, NR Cashman*. 2024. Tryptophan residues in TDP-43 and SOD1 modulate the cross-seeding and toxicity of SOD1. Journal of Biological Chemistry. 300(5):107207. doi: 10.1016/j.jbc.2024.107207
1co-first authors. *co-corresponding authors.
Hodges ED1, PW Chrystal1, T Footz, LP Doucette, NCL Noel, X Li, MA Walter, WT Allison. 2023. Disrupting the repeat domain of Premelanosome protein (PMEL) produces dysamyloidosis and dystrophic ocular pigment reflective of Pigmentary Glaucoma. International Journal of Molecular Sciences. 24:14423. 1co-first authors. doi: 10.3390/ijms241914423