Illuminating Galectin-3 Interactions to Disrupt Hepatic Fibrosis

项目摘要 人肝纤维化受Galectin-3与未知细胞之间的非共价相互作用的密切控制 肝星状细胞表面糖蛋白。在这里，我们寻求开发方法来识别这些 功能性糖蛋白然而，糖基化是一种翻译后修饰，其导致糖基化。 构建高度复杂和异质的聚糖分子，其结构难以预测 仅仅基于遗传密码。尽管在糖科学方面取得了重大进展，但实现对糖的选择性控制， 由聚糖和GBP介导的生物学事件仍然是一个重要的障碍。这个问题的核心是 分析蛋白质-聚糖相互作用的有限分辨率。聚糖主要表现为 蛋白质-糖蛋白相互作用为随后的生物学过程提供了背景。 过程在本申请中，我们提出了鉴定半乳糖凝集素-3和 肝星状细胞中的糖蛋白，并对这些结合导致的功能后果进行分类 人类生理学、发育和疾病背景下的事件。这些方法集成了技术 定量质谱遗传学和糖组学这项工作为一个关键问题提供了新的解决方案 在糖科学中，将为探索聚糖在药物发现中的应用开辟新的机会 和生物医学。

PROJECT SUMMARY Human liver fibrosis is intimately controlled by noncovalent interactions between Galectin-3 and unknown cell surface glycoproteins on hepatic stellate cells. Here, we seek to develop methodologies to identify these functional glycoproteins. However, glycosylation is a post-translational modification that results in the construction of highly complex and heterogeneous glycan molecules whose structures are challenging to predict based on the genetic code alone. Despite significant advances in glycoscience, achieving selective control over biological events mediated by glycans and GBPs remains a significant obstacle. At the heart of this problem is the limited resolution with which protein-glycan interactions are analyzed. Glycans are largely displayed as conjugates with proteins, and such protein-glycoprotein interactions provide context for the ensuing biological process. In this application, we propose approaches to identify the interactions between Galectin-3 and glycoproteins in liver stellate cells, and to catalogue the functional consequences resulting from these binding events in the context of human physiology, development, and disease. These approaches integrate techniques in quantitative mass spectrometry, genetics, and glycomics. This work provides novel solutions to a key problem in glycoscience and will open new opportunities for the exploration of glycans for applications in drug discovery and biomedicine.