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

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.