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

大麻最近在加拿大被联邦政府合法化，娱乐用大麻市场预计每年价值高达70亿美元。从科学上讲，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，但人们消费的是大麻植物的花，因为它们是有价值的代谢物。花朵表面被称为毛状体的微小毛发会产生一种名为“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，这些大麻素分子自发地分别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)。大麻花还在同一腺毛中产生大量芳香和树脂萜烯，这些萜烯是大麻气味的罪魁祸首。令人惊讶的是，决定大麻药理作用的化学物质都是在花朵表面的毛状体细胞小簇中产生的，但人们对这些细胞如何产生和储存大麻素类和萜类化合物知之甚少。由于过去法律对大麻的限制，对大麻植物的研究一直很困难。现在，研究环境正在迅速发生变化：2016年，塞缪尔实验室获得了新的加拿大创新基金会赠款，用于在不列颠哥伦比亚大学建造一个安全的大麻温室，加拿大卫生部使用大麻跟踪和许可系统的许可有了新的程序。*这一发现研究计划的目标是了解大麻花上的毛状体细胞如何产生和储存如此大量的大麻素和萜烯。花朵表面的这些微小细胞团是生产大麻的生化微型工厂。这项研究计划将有三个目标：查明大麻细胞中负责制造大麻类化合物的部分；发现油性和强效的大麻类化合物和萜类如何在不产生毒性的情况下通过细胞；以及测试细胞如何将代谢产物包装在毛状体的细胞壁中。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生产、运输和储存其代谢物的假说。发现代谢物是在哪里制造的，以及毒性影响是如何控制的，对于想要生产高价值大麻的生物技术专家来说，这是至关重要的信息。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参考。随着大麻成为加拿大的一种主流作物，大麻的细胞和分子生物学是迫切需要的基本知识。

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.