Defining the functional roles of MUC5AC and MUC5B in mucus in respiratory airways

粘液是肺部产生的果冻状物质，用来保护身体免受污染、细菌、病毒和其他环境因素的侵害。黏液的作用是捕获环境因子，通过所谓的？黏膜纤毛的自动扶梯吗?排列在大气道表面的细胞有细小的毛发，称为纤毛，它与黏液相互作用，捕获并清除肺部的碎片。纤毛的跳动使粘液向上移动到喉咙，在那里它被吞下。患有哮喘、囊性纤维化和慢性支气管炎等气道疾病的人不仅要不断地制造过多的粘液，而且产生的粘液比正常情况下更粘稠。这种粘稠的粘液不能被纤毛移动，导致气道阻塞。粘液是一种复杂的粘性混合物，由电解质、水和一种叫做粘蛋白的巨大的绳子状分子组成。大气道粘液中有MUC5AC和MUC5B两种粘蛋白。我们知道，在疾病中，两种粘蛋白的产生量要大得多，这有助于阻塞气道。此外，最近的研究表明，粘液凝胶中MUC5AC和MUC5B的比例可以改变纤毛移动粘液的方式，但目前尚不清楚这是如何发生的。鉴于此，我们的主要研究问题是：MUC5AC和MUC5B这两种粘蛋白是否产生了可以被纤毛以同样的效率移动的粘液凝胶，以及粘液凝胶的其他成分是否与粘蛋白相互作用以改变粘液的移动方式？为了回答这个问题，我们汇集了生物学和物理学的研究团队，以了解MUC5AC和MUC5B对黏液凝胶粘性的不同贡献。我们还将发现其他分子对于制造可从气道中清除的可移动粘液凝胶至关重要。了解黏液凝胶在健康和疾病中的组织将使人们能够设计出新的治疗方法来治疗气道阻塞。

Mucus is the jelly-like substance produced by the lungs to defend the body against pollution, bacteria, viruses and other environmental agents. Mucus acts to trap environmental agents and their removal from the lung is made possible by what is known as the ?mucociliary escalator?: Cells lining the surface of the large airways have tiny hairs called cilia which interact with mucus to trap and remove debris from the lungs. The beating action of the cilia moves the mucus up to the throat, where it is swallowed. Individuals suffering from airway diseases such as asthma, cystic fibrosis and chronic bronchitis face the constant struggle of not only making too much mucus, but that the mucus produced is stickier than normal. Such sticky mucus cannot be moved by the cilia, resulting in the airways becoming blocked.Mucus is a complex viscous mixture made up of electrolytes, water and extremely large, rope-like molecules called mucins. There are two types of mucins in the mucus of the large airways, MUC5AC and MUC5B. In disease we know that there is a much larger amount of both mucins produced, which contributes to blocking the airways. In addition, recent research suggests that the ratio of MUC5AC and MUC5B in the mucus gel can alter how the mucus is moved by cilia, but exactly how this happens is not currently understood.In light of this, our principal research question is: Do the two mucins, MUC5AC and MUC5B, make mucus gels which can be moved by cilia with equal efficiency, and do other components of the mucus gel interact with the mucins to alter how mucus is moved?To answer this question, we are bringing together research teams in Biology and Physics in order to understand the distinct contributions of MUC5AC and MUC5B to the stickiness of the mucus gel. We will also find out what other molecules are critical for creating a moveable mucus gel which can be cleared from the airways. Understanding the organisation of mucus gels in health and disease will enable the design of new treatments for people suffering with airway obstruction.