Dr. W. Ted Allison
PhD: Biology, University of Victoria, BC
Position: Associate Professor
Department of Biological Sciences
Centre for Prions and Protein Folding Diseases Neuroscience and Mental Health Institute Faculty of Science
Email: firstname.lastname@example.org Lab webpage: http://www.biology.ualberta.ca/Allison_Lab/
Kaiser DM1, M Acharya1, PLA Leighton1, H Wang, N Daude, S Wohgelmuth, B Shi, WT Allison*. 2012. Amyloid β Precursor Protein and Prion Protein have a conserved interaction affecting cell adhesion and CNS development.
PLoS ONE. 7(12):e51305. 1equal contributors. doi:10.1371/journal.pone.0051305
Fleisch VC1, PLA Leighton1, H Wang, LM Pillay, RG Ritzel, G Bhinder, B Roy, KB Tierney, DW Ali, AJ Waskiewicz, WT Allison*. 2013. Targeted mutation of the gene encoding prion protein in zebrafish reveals a conserved role in neuron excitability. Neurobiology of
Leighton PLA, WT Allison*. 2016. Protein misfolding in prion and
Zebrafish Models of Alzheimer & Prion Disease. We are creating transgenic and mutant zebrafish toward the goal of modelling 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
synaptogenesis, including through collaborative in vivo electrophysiology approaches.
1)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 PrPC is a receptor for Aβ; We have expanded this research space by showing that PrPC is also an interactor with the APP holoprotein. The interaction is occurs at the level of biochemistry and synergistic toxic knockdown when APP and PrPC are knocked down in zebrafish. Further investigations will dissect this interaction.
We assert that loss of protein function during misfolding, e.g. for APP and PrPC, contributes substantially to the etiology of neurodegen- eration. Disruption of APP or PrPC 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 PrPC 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.
3)Conserved functions of PrPC. We have
demonstrated that mammalian PrPC 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
4)Drug screens. We will deploy our engineered zebrafish into