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Mucin engineering for biomedical applications

Reference number
FFL15-0072
Start and end dates
170101-221230
Amount granted
11 640 000 SEK
Administrative organization
KTH - Royal Institute of Technology
Research area
Life Science Technology

Summary

Mucins are a family of glycoproteins that assemble to form the mucus layer that protects our wet epithelium, including our eyes, respiratory tract, gastrointestinal tract, and female reproductive tract. Mucins are central to high-impact and high value medical and technological issues. First, in health and medicine, mucins are key components in contraception, ageing, dry mouth and dry eye, and life threatening medical conditions such as gastric ulcers, cystic fibrosis, and Crohn's disease. Second, in addition to being an important part of our physiology, mucins is a multifunctional material that can be extracted, purified, and assembled into biomaterials. However because of the lack of tools, basic knowledge about its properties, and multidisciplinary approach, there has been barely any efforts to engineer solutions to repair failing mucus layer or to exploit the rich functionalities of mucins assembled in biomaterials. This project contains two work packages. First, we will conceive strategies to repair defective mucus layers by delivering exogenous mucins or by binding naturally occurring peptides to defective mucins. Second, we will develop mucin-based biomaterials that will set mucins as a new class of biopolymers to help solve vexing challenges faced by medical devices. This project will lead to fundamental discoveries around mucins, while establishing mucins as a reference biopolymeric tool to solve challenges faced by the biomedical, food, and cosmetic industries.

Popular science description

For thousands of years humans have been exploiting natural materials for their benefit. For example, wood-extracted cellulose fibers are used to make paper, seaweed-extracted alginates are used in yogurt and the animal-extracted hyaluronic acid is used in anti wrinkle creams. In this proposal we will study, use and manipulate mucins, i.e. molecules extracted from mucus, for medical applications. Mucins are the main components of mucus, the gel that covers our eyes, nose, mouth, lungs, stomach, gut and female reproductive tract. Mucin molecules give mucus its viscous texture. But mucins are also responsible for protecting us by acting like a sticky spider web, trapping pathogens such as viruses and bacteria. But sometimes, the mucus layer fails us. It is too thin or modified in some way, and cannot protect us anymore. This directly affects one health and leads to conditions such as inflammatory bowel disease, dry eye, dry mouth and vaginal dryness. In this project, we will develop new ways to provide relied for the millions suffering from deficiencies in their mucus layers. One way will be to delivery mucins extracted from animals to the mucosal surface. This will be done by first condensing the mucins into small particles that will then stick to the musoca and release the mucins. Another strategy will be to use small proteins naturally presenting the the mucus that seem to play an important role for the natural protective properties of mucus: trefoil factors. The second aspect of this proposal will be to use mucins to build new materials that can have interesting biomedical applications. Scientists recently discovered that mucus provides calming signals to our immune system. We will use that property to help the body accept the foreign material and decrease the risks of rejection. If successful, such mucin films could be use to prolong the lifetime of implantable medical devices such as the electrodes used in the brain to reduce tremor in Parkinson's disease. We will also develop mucins as carriers for probiotic bacteria. Probiotics can help balance the population of bacteria we have in our intestines and could potentially help treat many diseases even in infants. But getting the bacteria to he intestines is challenging since they are digested when passing through the stomach. We think that wrapping the bacteria in mucin gels could protect them enough so that they reach the intestines without any harm, improving the efficacy of probiotic treatments.