Maximizing Investigators' Research Award

摘要 我的实验室有两个主要感兴趣的领域：1)尾部锚定(TA)蛋白靶向和质量控制； 2)选择性自噬。鉴于选择性自噬的目标是有毒蛋白质聚集体和 破坏细胞器用于销毁，这两个研究领域具有很强的概念联系。在……里面 在许多情况下，我们都在回答有关底物选择性的类似问题：有什么区别 新合成的TA蛋白作为TA靶向内质网蛋白的底物 以线粒体为靶点的蛋白质？TA蛋白被错误定位为 线粒体作为天然线粒体TA蛋白的质控底物？什么 将明显受损的细胞器作为选择性自噬底物与健康的区分 细胞器？为了回答这些问题，我们正在剖析不同的分子机制 选择大小完全不同的衬底，并在非常不同的时间尺度上运行。我的实验室 以其在萌芽酵母中的生化重建工作而闻名，但最近 我们已经做了基因组学，定量酵母细胞显微镜和理论建模，以及 哺乳动物细胞的全基因组筛选。

ABSTRACT My lab has two main areas of interest: 1) tail-anchored (TA) protein targeting and quality control; 2) selective autophagy. Given that selective autophagy targets toxic protein aggregates and damaged organelles for destruction, these two research areas have strong conceptual ties. In many cases we are answering similar questions about substrate selectivity: What distinguishes newly-synthesized TA proteins as substrates for endoplasmic reticulum protein targeting from TA proteins targeted to mitochondria? What distinguishes TA proteins that are mistargeted to mitochondria as quality control substrates from native mitochondrial TA proteins? What distinguishes apparently damaged organelles as selective autophagy substrates from healthy organelles? To answer these questions, we are dissecting diverse molecular mechanisms that select substrates of grossly different sizes and operate on very different time scales. My lab is known for its biochemical reconstitution work in the budding yeast S. cerevisiae but more recently we have done genomics, quantitative yeast cell microscopy with theoretical modeling, and genome-wide screens in mammalian cells.