Investigation of mitosis in human cells using novel chemical inhibitors

使用新型化学抑制剂研究人体细胞有丝分裂

• 批准号: RGPIN-2017-04398
• 负责人: Golsteyn, Roy
• 金额: $ 2.04万
• 依托单位: University of Lethbridge
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=744743
• 关键词: Investigation; mitosis; human; cells; using

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.

我的研究项目致力于了解人类细胞如何分裂。 这很重要，因为细胞分裂有可能改变和影响未来的细胞。 细胞的许多部分已经使用基因组和生物化学方法鉴定。 我们现在可以研究这些部分如何协调像细胞分裂这样复杂的事件。 研究细胞如何分裂的一种方法是使用化学物质停止有丝分裂的一步。要找到这些化学物质，首先需要一个好的地方来寻找它们，比如植物。 我的实验室以前的工作发现，草原植物含有许多对人类有毒的化学物质。 这其中的原因很有趣;草原植物几千年来一直在与食草动物竞争，因此只有产生有毒化学物质的植物才能避免被动物（如布法罗）吃掉。 在许多方面，人类细胞与其他动物的细胞相似，因此，一些草原植物对人类细胞有毒。 然后，我的实验室测试了草原植物阻止人类细胞分裂的能力。 虽然有许多植物具有有趣的特性，但我们确定了六种具有我们正在寻找的效果。 我们现在正处于一个阶段，我们需要仔细描述这些化学物质，以确定它们是否真的含有抗有丝分裂化学物质。 首先，我们把精力集中在一种名为毯子花的植物上。 我们在粗提物中检测到它的抗有丝分裂活性，然后使用一系列测试，并与加拿大化学家合作纯化负责活性的化学物质。 我们发现的化学物质是新的，尽管它与其他植物中发现的一些化学物质相似，这有助于我们了解它的功能。 我们测试了这种我们命名为PP-006的化学物质是否可以作为一种科学工具来了解更多关于有丝分裂的信息。 PP-006以与其他已知化学品不同的方式阻止有丝分裂。 我们的研究为我们指出了一种新的机制，即细胞的一部分停止分裂，而另一部分继续分裂。 打个比方，开车时总是踩刹车。 这可能解释了为什么这种化合物是有毒的，但更重要的是，PP-006将帮助我们更好地了解细胞分裂是如何发生的。 我们正在研究其他五种也能抑制细胞分裂的植物提取物。 我们的研究有很多好处。我们将更多地了解人类细胞如何分裂，并更好地了解细胞分裂中可能发生的变化。 重要的是，我们的研究为学生提供了宝贵的培训经验，因为它涉及不同的主题，如植物学，细胞生物学和化学。 最后，我们发现的一些植物是原住民社区所知的，我们的研究为分享科学和传统知识创造了机会。 植物提取物库将成为加拿大新项目和合作中未来生物测试的宝贵资源。