Delineating the Multifunctional Role of the Mouse Submandibular Gland Protein (mSMGP)

描述小鼠颌下腺蛋白 (mSMGP) 的多功能作用

• 批准号: RGPIN-2021-03348
• 负责人: Myal, Yvonne
• 金额: $ 2.04万
• 依托单位: University of Manitoba
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2021
• 资助国家: 加拿大
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=742508
• 关键词: Delineating; Multifunctional; Role; Mouse; Submandibular

The submandibular gland is a major salivary gland in mammals. Located beneath the floor of the mouth, this gland produces close to two-thirds of normal (unstimulated) saliva secretions. While the digestive and humidifying functions of saliva are more familiar to most of us, saliva contains an abundance of proteins that carry out a huge range of biological functions. These functions are similar, but not identical, across mammalian species from mice to humans. Our lab has used scanning techniques (proteomics) to identify a large number of the proteins secreted by the submandibular gland in mice. We are particularly interested in the function of one protein in particular, called mSMGP, and how it might interact with some of the other proteins we have identified. These protein interactions are fundamental to many biological processes, but our current interest in mSMGP centres around our recent discovery that it can interfere with bacteria in the mouth, thus contributing to a perhaps lesser-known function of saliva: defence against microbial invasion. We are looking to understand these defensive properties of mSMGP more completely. Does it kill bacteria or simply inhibit their growth? What it is about this protein's structure that makes it dangerous to bacteria? Are other proteins in saliva required to help mSMGP carry out these defensive duties? The methods we will employ to answer these questions involve gene editing methods that can remove mSMGP from mice altogether. We will see what happens when mSMGP is absent, or when its structure is altered, by exposing bacteria to saliva from our engineered mice or to solutions of modified mSMGP. We will also use enhanced proteomic techniques to look for proteins that potentially interact with mSMGP. These techniques will involve attaching a "tag" to mSMGP so that its interactions with other proteins can be tracked. The knowledge we will gain from these studies will be compared to what we know about the version of this protein found in humans. Comparing the protein in these two species will be useful in many different fields, both in Canada and on the international stage. First, it will help us understand the importance of saliva and salivary proteins in defending our bodies against microbial attacks. Secondly, it will help us understand how the function of this protein has (or has not) been conserved over our evolutionary history. And finally, it will support health research because it will clarify both the usefulness and the limitations of using animal systems as models of human disease.

颌下腺是哺乳动物的主要唾液腺。这个腺体位于口底下方，产生接近三分之二的正常(未受刺激的)唾液分泌物。虽然我们大多数人对唾液的消化和增湿功能比较熟悉，但唾液中含有丰富的蛋白质，这些蛋白质具有广泛的生物功能。这些功能在从老鼠到人类的哺乳动物物种中是相似的，但并不完全相同。我们的实验室使用扫描技术(蛋白质组学)识别了小鼠下颌下腺分泌的大量蛋白质。我们特别感兴趣的是一种名为mSMGP的蛋白质的功能，以及它可能如何与我们已经识别的其他一些蛋白质相互作用。这些蛋白质相互作用是许多生物过程的基础，但我们目前对mSMGP的兴趣集中在我们最近的发现，即它可以干扰口腔中的细菌，从而有助于唾液的一种可能鲜为人知的功能：防御微生物入侵。我们希望更全面地了解mSMGP的这些防御属性。它是杀死细菌还是简单地抑制它们的生长？这种蛋白质的结构是什么让它对细菌构成危险？唾液中的其他蛋白质是否需要帮助mSMGP执行这些防御职责？我们将用来回答这些问题的方法包括基因编辑方法，这种方法可以完全从小鼠身上移除mSMGP。我们将通过将细菌暴露于我们改造的小鼠的唾液或改良的mSMGP溶液，来观察当mSMGP缺失时或其结构改变时会发生什么。我们还将使用增强的蛋白质组学技术来寻找可能与mSMGP相互作用的蛋白质。这些技术将包括在mSMGP上附加一个“标签”，以便可以跟踪它与其他蛋白质的相互作用。我们将从这些研究中获得的知识将与我们在人类中发现的这种蛋白质的版本进行比较。比较这两个物种中的蛋白质将在许多不同的领域有用，无论是在加拿大还是在国际舞台上。首先，它将帮助我们了解唾液和唾液蛋白质在保护我们的身体免受微生物攻击方面的重要性。其次，它将帮助我们理解这种蛋白质的功能在我们的进化史中是如何被(或没有)保守的。最后，它将支持健康研究，因为它将阐明使用动物系统作为人类疾病模型的有用性和局限性。