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

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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.