Lysosomes in the mammary gland : their role in mediating cell death

溶酶体是一种膜结合的小囊泡，称为细胞器，除了线粒体等其他细胞器外，还含有许多酶，这些酶可以分解DNA和蛋白质等大分子，线粒体是所谓的细胞动力源。溶酶体还有助于摧毁入侵细胞的细菌和病毒，在它们被运送到溶酶体后进行消化。溶酶体本质上是回收中心，因为它们分解陈旧和受损的成分，并将小分子回收到细胞质中，在那里它们被用来重建DNA、蛋白质和细胞器。有许多衰弱的遗传病是由溶酶体功能缺陷引起的，最近，溶酶体与阿尔茨海默氏症等神经退行性疾病有关，也与癌症有关。我们已经证明，在乳房哺乳后退化期间，溶酶体泄漏其内容物，从而导致乳房细胞的死亡。这一新发现对乳腺癌和其他溶酶体功能很重要的疾病具有重要意义。这个项目的目的是调查溶酶体是如何泄漏的，以及如何控制这一点。我们将使用一系列技术，包括创新的方法来识别新的蛋白质，并使用荧光和延时显微镜测量它们在细胞中的定位。我们还将调查这些蛋白质在破坏溶酶体并导致其有毒内容泄漏到细胞中可能起到的任何作用。我们希望这项工作将为杀死通常对其他类型的细胞死亡具有抵抗力的乳腺癌细胞提供新的想法。

Lysosomes are small membrane-bound vesicles, called organelles, that contain a number of enzymes that breakdown large molecules such as DNA and proteins in addition to other organelles such as mitochondria, the so-called powerhouse of the cell. Lysosomes also help to destroy bacteria and viruses that invade cells by digesting them after they have been delivered to the lysosome. Lysosomes are essentially recycling centres as they breakdown old and damaged components and recycle small molecules back to the cell cytoplasm where they are used to rebuild DNA, proteins and organelles. There are a number of debilitating inherited diseases that arise from defects in lysosome function and more recently, lysosomes have been associated with neurodegenerative diseases such as Alzheimer's and also with cancer. We have shown that lysosomes leak their contents during post-lactational regression of the breast and that this causes the death of the breast cells. This new discovery has important implications for breast cancer and other diseases where lysosome function is important. The aim of this project is to investigate how lysosomes become leaky and how this is controlled. We will use a range of techniques including innovative ways to identify novel proteins and measure their localisation in the cell using fluorescence and time-lapse microscopy. We will also investigate any role that these proteins may have in damaging lysosomes and causing them to leak their toxic contents into the cell. We hope that this work will provide new ideas for killing breast cancer cells, that are often resistant to other types of cell death.