Investigation of mitosis in human cells using novel chemical inhibitors

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My research program is dedicated to understanding how human cells divide. This is important because cell division has the potential to change and affect future cells. Many of parts of the cell have already been identified using genomic and biochemical approaches. We are at a stage where we can now study how these parts orchestrate an event as complex as cell division. One approach to study how cells divide is to use chemicals that stop one step of mitosis. To find these chemicals one first needs a good place to search for them, such as plants. Previous work from my laboratory found that prairie plants contain many chemicals that are toxic to humans. The reason for this is interesting; prairie plants have been in competition with grazing animals since millennia, therefore only plants that produced toxic chemicals were able to avoid being eaten by animals, such as buffalo. In many ways, human cells are similar to cells from other animals, therefore, some prairie plants are toxic to human cells. My laboratory then tested prairie plants for their capacity to stop human cells from dividing. Although there were many plants with interesting properties, we identified six that had the effect for which we were searching. We are now at a stage where we need to characterize these chemicals carefully to find if they truly contain anti-mitotic chemicals. To start, we focused our efforts on a plant named the Blanket flower. We detected its anti-mitotic activity in a crude extract, and then used a series of tests and collaborated with a Canadian chemist to purify the chemical that was responsible for the activity. The chemical we discovered was new, although it resembled some chemicals found in other plants, which helped us understand how it might function. We tested if the chemical, which we named PP-006, could be used as a scientific tool to learn more about mitosis. PP-006 blocks mitosis in a different way from other known chemicals. Our research points us to a novel mechanism in which one part of the cell stops dividing while another part continues to divide. An analogy would be to drive your car while always pressing on the brakes. It might explain why this compound is toxic, but more importantly, PP-006 will help us understand better how cell division occurs. We are investigating the five other plant extracts that also inhibit cell division. Our research has many benefits. We will learn more about how human cells divide and understand better how changes might occur in dividing cells. Importantly, our research provides valuable training experiences for students because it involves different topics, such as botany, cell biology, and chemistry. Finally, some of the plants that we identified are known to First Nations communities, and our research creates an opportunity to share scientific and traditional knowledge. The plant extract library will become a valuable resource for future biological testing in new projects and collaborations in Canada.