Maximizing Investigators' Research Award

最大限度地提高研究人员的研究奖

• 批准号: 10380617
• 负责人: Vladimir Denic
• 金额: $ 56.99万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-01 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10380617
• 关键词: Area; Autophagocytosis; Award; Biochemical; Cells; Endoplasmic Reticulum; Genomics; Mammalian Cell; Microscopy; Mitochondria; Molecular; Organelles; Proteins; Quality Control; Research; Research Personnel; Saccharomyces cerevisiae; Saccharomycetales; Tail; Theoretical model; Time; Work; Yeasts; genome wide screen; interest; protein aggregation; reconstitution

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.

摘要 我的实验室主要有两个研究领域：1）尾锚定蛋白（TA）靶向和质量控制; 2)选择性自噬考虑到选择性自噬针对有毒蛋白质聚集体， 破坏细胞器，这两个研究领域有很强的概念联系。在 在许多情况下，我们都在回答关于底物选择性的类似问题： 新合成的TA蛋白作为TA的内质网蛋白靶向的底物 针对线粒体的蛋白质是什么区分TA蛋白， 线粒体作为天然线粒体TA蛋白质的质量控制底物？什么 区分明显受损的细胞器作为选择性自噬基板从健康 细胞器？为了回答这些问题，我们正在解剖不同的分子机制， 选择尺寸大不相同的衬底，并在非常不同的时间尺度上操作。我的实验室 以其在芽殖酵母S.酿酒厂，但最近 我们做了基因组学，定量酵母细胞显微镜与理论建模， 哺乳动物细胞的全基因组筛选。