Uncovering the Mysteries of Cannabis: How Trichomes of Cannabis Produce their Unique Metabolites.

揭开大麻的奥秘：大麻毛状体如何产生其独特的代谢物。

• 批准号: RGPIN-2019-04592
• 负责人: Samuels, Anne
• 金额: $ 4.74万
• 依托单位: University of British Columbia
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=691361
• 关键词: Uncovering; Mysteries; Cannabis; How; Trichomes

Cannabis was recently made federally legal in Canada, and the recreational cannabis market is projected to be worth up to $7 billion per year. Scientifically, we know very little about the biology of this economically and socially important plant (Cannabis sativa). Despite the iconic cannabis leaf, it is the flowers of the cannabis plant that are consumed for their valuable metabolites. Tiny hairs called trichomes on the flower surface produce the chemicals called 'cannabinoids', including tetrahydrocannabinolic acid and cannabidiolic acid. When heated, these cannabinoid molecules spontaneously form the psychoactive compound tetrahydrocannabinol (THC) and the medicinal compound cannabidiol (CBD), respectively. Cannabis flowers also produce high quantities of fragrant and resinous terpenes in the same glandular trichomes, and these terpenes are responsible for the smell associated with cannabis. It is astonishing that the chemicals that determine the pharmacological effects of cannabis are all produced in tiny clusters of trichome cells on the flower surface, yet very little is known about how these cells produce and store cannabinoids and terpenes. Due to the past legal restrictions on cannabis, it has been difficult to study the cannabis plant. Now the research landscape is rapidly changing: in 2016, the Samuels lab was awarded a new Canadian Foundation for Innovation grant to build a secure cannabis greenhouse at UBC, and there are new procedures for Health Canada permits using the Cannabis Tracking and Licencing System. ******The goal of this discovery research program is to understand how the cells in the trichomes on cannabis flowers produce and store such large quantities of cannabinoids and terpenes. These tiny cell clusters on the surface of the flower are the biochemical micro-factories of cannabis production.******This research program will have three objectives: to pinpoint the parts of the cannabis cells responsible for making the cannabinoids; to discover how the oily and potent cannabinoids and terpenes can move through the cells without having a toxic effect; and to test how the cells package the metabolites in the cell wall of the trichomes. The Samuels lab expertise is in plant cell biology, especially in using advanced microscopy tools such as live-cell multi photon imaging, cryo-fixation, and electron microscopy to probe inside of cells. We will use these tools to test hypotheses of how the cannabis cells produce, traffic, and store their metabolites. Discovering where the metabolites are made, and how toxic effects are controlled, is vital information for biotechnologists who want to produce high-value cannabinoids. How cannabis stores its products in the cell wall will influence retention or release, so this information will inform best practices in drying, extraction, and storage. The cell and molecular biology of cannabis is fundamental knowledge that is urgently required as cannabis becomes a main stream crop in Canada.

大麻最近在加拿大被联邦政府定为法律的，娱乐性大麻市场预计每年价值高达70亿美元。科学上，我们对这种经济和社会重要植物（大麻）的生物学知之甚少。尽管有标志性的大麻叶，但大麻植物的花被消耗为其有价值的代谢物。花表面被称为毛状体的微小毛发产生被称为“大麻素”的化学物质，包括四氢大麻酚酸和大麻二酚酸。当加热时，这些大麻素分子分别自发形成精神活性化合物四氢大麻酚（THC）和药用化合物大麻二酚（CBD）。大麻花在相同的腺毛中也产生大量的芳香和萜烯，这些萜烯是与大麻相关的气味的原因。令人惊讶的是，决定大麻药理作用的化学物质都是在花表面的微小毛状体细胞簇中产生的，但人们对这些细胞如何产生和储存大麻素和萜烯知之甚少。由于过去对大麻的法律的限制，对大麻植物的研究一直很困难。现在，研究领域正在迅速发生变化：2016年，Samuels实验室获得了新的加拿大创新基金会资助，在UBC建立了一个安全的大麻温室，并且使用大麻跟踪和许可系统获得加拿大卫生部许可证的新程序。** 这项发现研究计划的目标是了解大麻花上毛状体中的细胞如何产生和储存如此大量的大麻素和萜烯。花表面的这些微小细胞簇是大麻生产的生化微型工厂。该研究计划将有三个目标：查明大麻细胞中负责产生大麻素的部分;发现油性且强效的大麻素和萜烯如何在细胞中移动而不产生毒性作用;并测试细胞如何包装毛状体细胞壁中的代谢物。Samuels实验室的专长是植物细胞生物学，特别是使用先进的显微镜工具，如活细胞多光子成像，冷冻固定和电子显微镜来探测细胞内部。我们将使用这些工具来测试大麻细胞如何产生，运输和储存其代谢产物的假设。发现代谢物的产生地点以及如何控制毒性作用，对于想要生产高价值大麻素的生物技术人员来说是至关重要的信息。大麻如何将其产品储存在细胞壁中将影响保留或释放，因此这些信息将为干燥，提取和储存的最佳实践提供信息。大麻的细胞和分子生物学是基本知识，随着大麻成为加拿大的主要作物，迫切需要这些知识。