RESEARCH PROJECTS

ALLISON RESEARCH LAB

NeuroDegeneration & Functional Regeneration

University of Alberta

Edmonton, Alberta, Canada

 

PUBLIC SUMMARY

Our research focusses on two main goals:  1) Discovering and understanding genes that turn stem cells into cone photoreceptors that will function to restore vision;  2) Understanding how protein mis-folding leads to cell death in diseases like Alzheimer Disease and Mad Cow Disease.  To address these aims we use an emerging model in biomedicine - the zebrafish.  Along the way we have opportunity to discover interesting facets of the evolution of how fish see the world, and we relate this to the varied and fascinating behaviours of other fishes. Fishes have excellent vision and use their sight for feeding, avoiding predators and breeding.


Regenerating Cone Photoreceptors:  Fish have rod and cone photoreceptors in their retinas (lining the back of the eye), very similar to humans. These include multiple cones (like our red, green & blue cones) that detect light during the day to permit colour vision.  Unlike us, fish are able to replace their photoreceptors when the cells are damaged.  The fish do this through stem cells that are present throughout their retina.  If we can learn what genes, cells and biological processes are used by fish to turn stem cells into photoreceptors, we may be able to deploy such information in humans as treatment for vision loss.  Importantly, we are also paying much attention to how these regenerated cones reconnect to the remaining cells in the retina - proper rewiring will be required for any such therapy to be practical. 

  1. Any contribution toward our efforts to repair vision loss or understand genetics of Alzheimer Disease would be highly valued, impactful and respected. Arrangements can be managed through the Faculty of Science Assistant Dean - Development.  Please contact Dr. Ted Allison to learn about how your support would help.

  1. NSERC                PrioNet Canada, a Network of Centres of Excellence

  2. CIHR                   Alberta Prion Research Institute, Alberta Innovates Biosolutions

  3. AHFMR               Alzheimer Society of Canada

  4. CFI                      Team to Prevent Blindness

  5. Alzheimer Society of Alberta & Northwest Territories

SCIENTIFIC SUMMARY HERE.   

PUBLICATIONS HERE.

Unique Animal Models of Alzheimer & Mad Cow Disease:  We use zebrafish to understand interactions of proteins that are notorious in two distinct diseases: Alzheimer Disease and Prion Disease.  The latter includes ‘mad cow disease’ (a.k.a. Bovine Spongiform Encephalopathy, BSE), Chronic Wasting Disease (CWD) in elk and deer, and Creutzfeldt–Jakob Disease in humans.  Alzheimer and prion diseases are similar in that a protein that is abundant in our brains changes from its normal shape to a mis-folded form that  aggregates and leads to cell death and dementia.  We have two overarching goals:  i. Creating zebrafish that develop these diseases (including those that can be infected with prion disease);  ii. Understanding the relationships and interactions between the notorious proteins that mis-fold in these diseases and other proteins that are believed to participate in disease. The latter has revealed unexpected linkages between the two distinct diseases, supporting other workers internationally who have identified molecular linkages between Alzheimer and Prion Diseases.

FUNDING

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Why zebrafish?  The zebrafish is a hardy pet store fish that has gained a prominent reputation amongst biologists and biomedical researchers over the past decade.  In short, these fish marry the advantages of several more traditional research paradigms:

  1. -like the fruit fly, many zebrafish can be maintained inexpensively and mutant fish can be bred efficiently. Unlike flies, zebrafish have genes and brains somewhat similar to humans;

  2. -like cells grown in a dish, the young fish can be grown in small dishes, allowing many treatments to be applied by robots and efficient screening of drugs to explore if they can treat disease.  Unlike cells in a dish, the zebrafish has appropriate interactions and states of cells similar to an intact brain (ventricles, blood-brain-barrier, glial interactions, vasculature, immune system...); 

  3. -like mice, zebrafish have genetic pathways and an architecture of cells in the brain that are very similar to those of humans.  These similarities are not as strong as mice, which are more closely related to humans, but the similarities are impressive none-the-less.  For example we find that many genes from humans can replace those of zebrafish.  Thus zebrafish can be a very useful complement to mice, in large part because we can efficiently change the expression of genes in the fish.

  4. Finally, it is noteworthy that zebrafish have excellent vision, an innate robust ability to regenerate damaged brains, and the ability to learn and perform behaviours that allow us to assess neurodegeneration and restoration of function following regeneration.