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

了解生物活性植物化合物的细胞功能，可以为包括健康在内的一系列领域对人类的影响提供独特的见解。丹参酮2A从红鼠尾草中提取，提供了这样一种有趣的化合物，具有几个世纪的健康相关用途，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，为未来的研究提供强大而稳定的背景。在本项目中，我们将利用易处理的微生物系统Dictyostelium disideum来研究丹参酮2A的分子机制，重点研究mTOR信号传导。我们已经证明盘基骨菌中的mTOR信号是由丹参酮2A调节的，并且已经确定了这种作用所必需的关键蛋白，为其分子机制提供了独特的见解。构效关系研究也强调了具有增强效力潜力的化合物。作为具有mTOR信号级联经验的人类/哺乳动物研究专家，该项目还将通过与Pardo博士的合作，涉及关键的转化方面。除了提供关键的相关动物/人类模型来验证发现之外，他还将提供尖端的研究方法，例如基于质谱的方法来鉴定Dictyostelium和哺乳动物细胞裂解物中的丹参酮2A相互作用蛋白。因此，该项目将为了解植物化学物质丹参酮2A的分子细胞生物学提供协同进展，并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.