Zebrafish help find new treatments for Alzheimer's disease

Karen Watanabe-Sailor, associate professor in the School of Mathematical and Natural Sciences at Arizona State University's West campus, recently received funding from the U.S. Army Corps of Engineers, Engineer Research and Development Center for a three-year project involving the effects of acetylcholine on zebrafish. This project is rooted in pharmacology and could lead to a new treatment for Alzheimer’s disease.

Here, Watanabe-Sailor talks about the study and its possibilities.

Question: Will ASU students be involved in conducting this research? If so, how? What kind of impact would this research have on their futures?

Answer: I currently have two students who are working on this project for academic research credit, but I would like to find a few more who have an interest in working at the interface of math, biology and computing.  

As a mentor, I try to find projects for students that will help them achieve their academic and career goals. With that said, this project could help students interested in getting a job at an environmental consulting company after graduation, for example; students interested in graduate school or a professional school (e.g., in medicine, pharmacy or public health) can strengthen their applications by working on the project and becoming a co-author on a published paper.

Q: How do you hope to put the results of this project to use?

A: Acetylcholinesterase inhibitors are chemicals (both drugs and toxicants) that prevent the degradation of a neurotransmitter, acetylcholine. Therapeutically, i.e., used as a drug, reversible acetylcholinesterase inhibitors are used to treat Alzheimer's disease. When too much acetylcholine accumulates, it overstimulates two different receptors that control a wide variety of body functions. This project is focused on the adverse effects of acetylcholinesterase inhibition from exposure to chemicals such as organophosphates and carbamates used as pesticides and fungicides in agricultural applications. A goal of the project is to develop a mathematical/computational model of an adverse outcome pathway for acetylcholinesterase inhibition in zebrafish. This model could then be used as a tool to predict outcomes for a variety of acetylcholinesterase inhibitors and their effect [or effects] on the organisms.

Q: How will this project influence your future work as a scientist? As a professor?

A: One theme in my research focuses on adverse outcome pathways for the effects of chemicals on reproduction in fathead minnows. This project builds upon my existing knowledge and expertise in constructing quantitative adverse outcome pathways, and will allow my research group to expand into a new area.

ASU's West campus recently launched a bachelor's degree in pharmacology/toxicology. I anticipate teaching a pharmacology/toxicology class in the near future and will be able to use results from this research as a teaching tool to illustrate how chemicals affect different scales of biological organization from interactions at the molecular level to cells and ultimately the organism.