Unravelling the molecular mechanisms of organelle interaction

Research on organelle cooperation is an emerging field in modern cell biology and biomedical sciences because of its key role in organelle function and its impact on developmental and physiological processes. Peroxisomes are multifunctional oxidative organelles that are essential for human health and development. They play vital roles in lipid metabolism, including both synthesis and breakdown, and are increasingly recognised for their involvement in cellular signalling (Silva BBA 2020, 1867:118800). Peroxisomal lipid metabolism requires close coordination with the endoplasmic reticulum (ER), mediated via membrane contact sites. Previously, we discovered that these peroxisome-ER contacts are important for inter-organelle lipid transfer, peroxisome formation and positioning, and are mediated by the acyl-CoA binding proteins ACBD4 and ACBD5 present in the peroxisomal membrane (Costello 2017, JCB 216:331; Kors 2022, JCB 221:e202003143). Despite their importance in cellular lipid metabolism and human health, the physiological functions of many ACBD proteins remain unclear (Islinger BBA 1867:118675). This project aims to address the fundamental question: How do ACBD4 and ACBD5 regulate cellular lipid metabolism, organelle contacts, and developmental processes? To investigate this, we will integrate molecular cell biology techniques with advanced imaging, omics approaches, and genetics, using multiple model systems, including mammalian cells, zebrafish, and fly. Our approach will provide critical insights into how ACBD4 and ACBD5 orchestrate lipid metabolism and organelle communication at molecular, cellular and physiological levels. Ultimately, this research could reveal novel therapeutic strategies targeting age-related disorders and metabolic diseases associated with dysregulated organelle communication.