Control of Cell Signalling and Membrane Trafficking Pathways by Phosphoinositide Regulatory Networks.

我们的细胞被分成不同的膜结合区室，其中一些形成了将货物运输进出细胞的重要途径。这些膜运输途径控制关键的细胞过程，包括营养摄取、活化生长因子受体的清除以及激素和神经递质的分泌。然而，我们对膜运输系统的理解仍然不完整。我们正在研究由称为磷酸肌醇的专门信号脂质控制膜运输途径。磷脂酰肌醇（PI）是细胞膜上的必需脂质，在细胞生长和发育中具有重要作用。PI代谢缺陷与许多人类疾病有关，包括癌症、糖尿病和神经退行性疾病。了解细胞如何维持和使用这些信号分子是至关重要的。我们的研究整合了细胞生物学，生物化学和遗传策略，以揭示PI信号在膜运输和细胞信号传导途径中的作用，以了解细胞如何响应环境中的线索，如生长因子，营养素和压力。这些研究与神经元的生物学特别相关，因为PI信号传导的缺陷导致神经和神经退行性疾病，包括唐氏综合征，阿尔茨海默病和帕金森病。我们的长期目标是开发用于治疗由PI信号传导和膜运输缺陷引起的疾病的新疗法。

Our cells are divided into distinct membrane-bound compartments some of which form essential pathways that transport cargo into and out of cells. These membrane trafficking pathways control key cellular processes including nutrient uptake, clearance of activated growth factor receptors, and the secretion of hormones and neurotransmitters. However our understanding of membrane trafficking systems remains incomplete. We are studying the control of membrane trafficking pathways by specialized signalling lipids named phosphoinositides. Phosphoinositides (PI) are essential lipids in cellular membranes that have important roles in cell growth and development. Defects in PI metabolism have been implicated in many human diseases including cancer, diabetes, and neurodegenerative disorders. It is vital that we understand how cells maintain and use these signalling molecules. Our research integrates cell biology, biochemistry, and genetic strategies to uncover roles for PI signalling in membrane trafficking and cell signalling pathways to understand how cells respond to cues in their environment, such as growth factors, nutrients, and stress. These studies are especially relevant to the biology of neurons, as defects in PI signalling result in neurological and neurodegenerative disorders including Down’s syndrome, Alzheimer’s disease, and Parkinson’s disease. Our long-term goal is to develop new therapeutics for the treatment of diseases caused by PI signalling and membrane trafficking defects.