Bridging the Glycome and Proteome with Chemical Biology

用化学生物学连接糖组和蛋白质组

• 批准号: 10798880
• 负责人: Mia L Huang
• 金额: $ 8.65万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10798880
• 关键词: Binding; Binding Proteins; Biochemical; Biology; Cell Communication; Cell Surface Proteins; Cell fusion; Cell surface; Cells; Chemicals; Development; Drug Targeting; Environment; Fetal Development; Fetus; Galectin 3; Genetic; Health; Label; Maintenance; Maps; Mediation; Methods; Modeling; Molecular; Mothers; Organ; Placenta; Polysaccharides; Pregnancy; Process; Proteins; Proteome; Signal Pathway; Structure; Techniques; cell behavior; experimental study; interest; sugar

PROJECT SUMMARY During pregnancy, the proper development of the placenta is essential to maintain the health of the fetus and mother; however, we still do not have a clear understanding of how certain components of the placenta normally form. We are interested in how the synctitiotrophoblast barrier is formed through cellular fusion, and to understand this process, we will focus on the proteins presented on the outside of the barrier called cell surface proteins (CSPs). CSPs are regulators of cell-cell interactions and help cells respond to their environment, making them biologically important and relevant drug targets. However, CSPs are challenging to study, because they are in low abundance and are covered with sugar molecules called glycans. These glycans are highly variable structures that cannot be predicted, requiring experimental evidence to ascertain their composition. One of the most important functions of these glycans is to interact with glycan-binding proteins (GBPs). GBPs bind to glycans on the cell surface, resulting in downstream changes to cell behavior. GBPs, like galectin-3, have been shown to be necessary for normal fetal development and placental cell fusion, but discovering their mechanism of action is challenging, as the weak and dynamic interactions between glycans and GBPs are not easy to capture. To overcome these limitations, we have developed two new techniques that allow us to label and identify CSPs and galectin-3 interactors in live cells. We will apply these methods to a model of placental cell fusion to understand the factors that lead to successful barrier formation. Once critical CSPs and galectin-3 interactors are uncovered, we will perform genetic and biochemical experiments to determine their functions in detail. We will map the signaling pathways within the cell that allow for fusion, as well as the composition of glycans that allow for GBP interactions.

项目摘要 怀孕期间，胎盘的适当发育对于维持胎儿的健康至关重要 母亲;但是，我们仍然对胎盘的某些成分通常没有清楚地了解 形式。我们对如何通过细胞融合形成突触性肌细胞屏障以及对 了解这一过程，我们将重点放在称为细胞表面的屏障外部的蛋白质上 蛋白质（CSP）。 CSP是细胞相互作用的调节剂，并帮助细胞对其环境做出反应，使得 它们在生物学上重要且相关的药物靶标。但是，CSP具有挑战性，因为他们 丰度低，并被称为聚糖的糖分子覆盖。这些聚糖很高 无法预测的可变结构，需要实验证据来确定其组成。一 这些聚糖最重要的功能是与聚糖结合蛋白（GBP）相互作用。 Gbps结合到 在细胞表面上的聚糖，导致下游会改变细胞行为。像Galectin-3一样，Gbps已经 证明是正常胎儿发育和胎盘细胞融合所必需的，但发现其机制 动作是具有挑战性的，因为聚糖和Gbps之间的弱和动态互动并不容易 捕获。为了克服这些局限性，我们开发了两种新技术，使我们能够标记和识别 CSP和Galectin-3在活细胞中相互作用。我们将将这些方法应用于胎盘细胞融合模型 了解导致成功形成障碍的因素。一旦关键的CSP和Galectin-3相互作用者是 未发现，我们将执行遗传和生化实验，以详细确定其功能。我们将 绘制允许融合的电池内的信号通路，以及允许的聚糖的组成 用于GBP相互作用。

项目成果

Proximity labeling technologies to illuminate glycan-protein interactions.

邻近标记技术阐明聚糖-蛋白质相互作用。

• DOI: 10.1016/j.cbpa.2022.102233
• 发表时间: 2023
• 期刊: Current opinion in chemical biology
• 影响因子: 7.8
• 作者: Reeves,AbigailE;Huang,MiaL
• 通讯作者: Huang,MiaL

Surfaceome Profiling Identifies Basigin-Chaperoned Protein Clients.

表面组分析可识别 Basigin 陪伴的蛋白质客户。

• DOI: 10.1002/cbic.202300073
• 发表时间: 2023
• 期刊: Chembiochem : a European journal of chemical biology
• 作者: Vilen,Zak;Joeh,Eugene;Lee,Elizabeth;Huang,MiaL
• 通讯作者: Huang,MiaL

Mapping glycan-mediated galectin-3 interactions by live cell proximity labeling.

• DOI: 10.1073/pnas.2009206117
• 发表时间: 2020-11-03
• 期刊: Proceedings of the National Academy of Sciences of the United States of America
• 影响因子: 11.1
• 作者: Joeh E;O'Leary T;Li W;Hawkins R;Hung JR;Parker CG;Huang ML
• 通讯作者: Huang ML

Chemoproteomic mapping of human milk oligosaccharide (HMO) interactions in cells.

• DOI: 10.1039/d2cb00176d
• 发表时间: 2022-11-30
• 期刊: RSC CHEMICAL BIOLOGY
• 影响因子: 4.1
• 作者: Hassan, Abdullah A.;Wozniak, Jacob M.;Vilen, Zak;Li, Weichao;Jadhav, Appaso;Parker, Christopher G.;Huang, Mia L.
• 通讯作者: Huang, Mia L.

Chemical editing of proteoglycan architecture.

• DOI: 10.1038/s41589-022-01023-5
• 发表时间: 2022-06
• 期刊: NATURE CHEMICAL BIOLOGY
• 影响因子: 14.8
• 作者: O'Leary, Timothy R.;Critcher, Meg;Stephenson, Tesia N.;Yang, Xueyi;Hassan, Abdullah A.;Bartfield, Noah M.;Hawkins, Richard;Huang, Mia L.
• 通讯作者: Huang, Mia L.