Organelle dynamics and function in the late endocytic pathway

细胞由专门的细胞器(每个细胞内的小器官)隔开，包括蛋白质在内的货物通过小泡(小气泡被由一种名为磷脂的脂肪物质制成的薄膜包围，并点缀着蛋白质)在这些隔间之间移动。一些货物被细胞表面形成的小泡吸收到细胞内，这些小泡将货物运送到称为内小体、内溶体和溶酶体的细胞器中。溶酶体充当酶的存储细胞器，这些酶降解从细胞表面或细胞其他部分输送的货物。降解发生在由内酶体和溶酶体融合形成的内溶酶体中。溶酶体是通过一种目前知之甚少的过程从内溶酶体内再生出来的，我们将对此进行研究。然后，这些溶酶体可以被重复使用。我们的目标是鉴定和研究构成实现和调节溶酶体再生所必需的机制的蛋白质。我们的工作将帮助我们更好地理解为什么我们正在研究的细胞器如此动态，并解释它们内部的环境是如何被调节的，以至于内溶酶体是货物降解的如此有效的场所，而溶酶体如此好地储存降解酶。在许多疾病中，细胞表面和/或膜向溶酶体的运输出现缺陷。这些疾病包括罕见的遗传性疾病，如溶酶体储存障碍，以及更常见的疾病，如糖尿病、动脉粥样硬化和神经退行性疾病，以及微生物破坏膜运输系统以感染细胞的传染病。从长远来看，我们的工作将有助于开发更好的方法，将药物靶向细胞内的特定部位，以进行更具体的药物治疗。

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.