Employing a tractable microbial model to investigating the molecular cell biology of the phytochemical Tanshinone 2A

了解具有生物活性的植物化合物的细胞功能可以为人类在包括健康在内的一系列领域中的影响提供独特的见解。丹参酮2A来源于丹参，提供了一种有趣的化合物，具有数百年的健康相关用途，但其分子机制尚不清楚。确定T2A在细胞和分子水平上的功能为未来的研究提供了一个强大而稳定的背景。在这个项目中，我们将利用易驯化的微生物系统盘基网柄菌来研究丹参酮2A的分子机制，重点是mTOR信号转导。我们已经证明了Dictyostelius中的mTOR信号是由丹参酮2A调节的，并且已经确定了这一作用所必需的关键蛋白，为其分子机制提供了独特的见解。结构-活性关系研究也强调了具有增强效力的潜力的化合物。该项目还将通过与帕尔多博士的合作，涉及关键的翻译方面。帕尔多博士是一名人类/哺乳动物研究专家，在mTOR信号级联方面具有经验。除了提供关键的相关动物/人体模型来验证发现外，他还将提供尖端研究方法，例如基于质谱学的方法，从网柄苔藓和哺乳动物细胞裂解物中识别丹参酮2A相互作用蛋白。因此，该项目将在理解植物化学物质丹参酮2A的分子细胞生物学方面取得协同进展，最终对改善社会健康产生影响。

Understanding the cellular function of bioactive plant compounds provides unique insight to effects in humans in a range of areas including health. Tanshinone 2A derived from Red Sage, provides one such interesting compound with centuries of health-associated use, yet its molecular mechanisms remains unclear. Defining how T2A functions at a cell and molecular level with provide a strong and stable background for future research. In this project, we will employ the tractable microbial system, Dictyostelium discoideum, to investigate the molecular mechanism of Tanshinone 2A, focusing on mTOR signalling. We have shown mTOR signaling is regulated by Tanshinone 2A in Dictyostelium, and have identified key proteins necessary for this effect, providing unique insight to its molecular mechanism. Structure-activity relationship studies have also highlight compounds with potential for increased potency. The project will also involve critical translational aspects through collaboration with Dr Pardo, as a human/mammalian research expert with experience in the mTOR signaling cascade. In addition to providing key relevant animal/human models to validate discoveries, he will also provide cutting-edge research approaches such as mass-spectrometry-based approaches to identify Tanshinone 2A interactor protein from Dictyostelium and mammalian cell lysates. This project will therefore provide synergistic advances in understanding the molecular cell biology of the phytochemical Tanshinone 2A with an ultimate impact on improving societal health.