Unravelling the molecular mechanisms of organelle communication in the regulation of cellular lipid metabolism and developmental processes. (4568)

细胞器合作研究是现代细胞生物学和生物医学科学的一个令人兴奋的新领域，因为它与细胞器的功能密切相关，并对发育和生理过程产生影响。过氧化物酶体是一种多功能的氧化细胞器，对人体健康和发育至关重要，在脂质合成和分解中起着重要的协同作用。过氧化物酶体在信号传导和细胞过程微调中的重要作用正在出现，这将它们整合到相互作用的细胞室的复杂网络中（Silva BBA 2020, 1867:118800）。过氧化物酶体脂质代谢需要与内质网（ER）协调，通过膜接触介导。此前，我们发现这些过氧化物异构体接触对细胞器间脂质转移、过氧化物异构体形成和定位很重要，并由过氧化物异构体膜上的酰基辅酶a结合蛋白ACBD4/5介导（Costello 2017, JCB 216:331; Kors 2022, JCB 221:e202003143）。尽管ACBD蛋白对细胞脂质代谢和人体健康具有重要意义，但许多ACBD蛋白的生理功能尚不清楚（Islinger BBA 1867:118675）。因此，这个多学科项目将解决与通过细胞器间通信调节和协调细胞器活动的分子机制相关的基本问题。它将结合分子细胞生物学方法与组学和遗传学方法，以及新的细胞和体内模型和工具（斑马鱼，苍蝇）。我们将使用分子细胞生物学，发育生物学和体内方法，以及尖端的成像技术，阐明ACBD4/5蛋白如何协调细胞脂质代谢，细胞器接触和发育过程。我们的方法将揭示ACBD4/5蛋白在分子、细胞和生理水平上协调脂质代谢和细胞器通信网络的机制和作用。通过这种多学科的方法，我们的目标是对细胞脂质代谢和细胞器通信网络的基本调节获得重要的新见解，这可能最终揭示治疗这些过程失调的年龄相关疾病的新策略。

Research on organelle cooperation represents an exciting new field in modern cell biology and biomedical sciences because of its close relation to organelle functionality and its impact on developmental and physiological processes.Peroxisomes are multifunctional, oxidative organelles that are essential for human health and development and play vital cooperative roles in lipid synthesis and breakdown. Important roles for peroxisomes in signalling and the finetuning of cellular processes are emerging, which integrate them in a complex network of interacting cellular compartments (Silva BBA 2020, 1867:118800).Peroxisomal lipid metabolism requires coordination with the endoplasmic reticulum (ER), mediated via membrane contacts. Previously, we discovered that these peroxisomeER contacts are important for inter-organelle lipid transfer, peroxisome formation and positioning, and are mediated by the acyl-CoA binding proteins ACBD4/5 present in the peroxisomal membrane (Costello 2017, JCB 216:331; Kors 2022, JCB 221:e202003143). Despite their importance to cellular lipid metabolism and human health, the physiological functions of many ACBD proteins remain unclear (Islinger BBA 1867:118675).This multi-disciplinary project will therefore address fundamental questions related to the molecular mechanisms that regulate and coordinate organelle activities via inter-organelle communication. It will combine molecular cell biology approaches with omics and genetic approaches as well as new cellular and in vivo models and tools (zebrafish, fly). We will use molecular cell biology, developmental biology and in vivo approaches, as well as cutting edge imaging techniques, to elucidate how ACBD4/5 proteins orchestrate cellular lipid metabolism, organelle contacts and developmental processes.Our approaches will reveal the mechanisms and roles of ACBD4/5 proteins in orchestrating lipid metabolism and organelle communication networks at the molecular, cellular and physiological level. With this multi-disciplinary approach, we aim to obtain crucial new insights into the fundamental regulation of cellular lipid metabolism and organelle communication networks, which could ultimately reveal new strategies to treat age-related disorders where these processes are dysregulated.