Organelle dynamics and function in the late endocytic pathway

点击翻译按钮获取中文摘要

Cells are compartmentalized by specialized organelles (little organs within each cell), and cargo including proteins is moved between these compartments by the trafficking of vesicles (little bubbles surrounded by a thin membrane made of a fatty substance called phospholipid and studded with proteins). Some of the cargo is taken up into the cells by vesicles formed at the cell surface that deliver their cargo to organelles called endosomes, endolysosomes and lysosomes. Lysosomes act as storage organelles for enzymes that degrade cargo that is delivered from the cell surface or other parts of the cell. Degradation occurs in endolysosomes formed by the fusion of endosomes with lysosomes. Lysosomes are regenerated from endolysosomes by a process that is currently poorly understood and which we will study. These lysosomes can then be re-used. We aim to identify and study the proteins that make up the machinery necessary to achieve and regulate the regeneration of lysosomes. Our work will help us to understand much better why the organelles we are studying are so dynamic and to explain how the environment within them is regulated such that endolysosomes are such an efficient site for cargo degradation and lysosomes work so well to store the degradative enzymes. There are many diseases in which defects in the cell surface and/or in membrane traffic to lysosomes occur. These include rare genetic diseases such as the lysosomal storage disorders and more common diseases including diabetes, atherosclerosis and neurodegenerative diseases as well as infectious diseases where microbes subvert the membrane traffic system in order to infect cells. In the long term our work will contribute to developing better ways of targeting drugs to particular sites within cells for more specific drug therapies.