Is Lyn tyrosine kinase a predictor of severe, persistent multi-trait asthma and allergy?

哮喘是澳大利亚的一个主要健康问题，在任何时候影响超过10%的人口，超过25%的人口在他们生命的一个阶段。虽然公众认为哮喘治疗改善了疾病的管理，但每年有700多人死于严重哮喘，并且因急性发作（突然恶化）而住院是澳大利亚和大多数发达国家医疗保健负担中最昂贵的组成部分之一。目前还没有分子标记物可以预测谁会患上严重的哮喘，也没有特异性的治疗方法来逆转严重的哮喘恶化。该项目将使用先进的分子生物学方法来研究一种名为林恩的分子是否可能很重要。林恩酪氨酸激酶是参与跨细胞膜传递信息的基因家族的成员。这种酶在血细胞中表达，并参与有关感染，免疫和过敏反应的机制。为了进一步理解这种酶在整个动物中的作用，我们已经产生了不能产生林恩蛋白的小鼠（林恩缺陷小鼠）。在哮喘的动物模型中，我们知道如果林恩不起作用，就会发生严重和持续的哮喘。我们还进行了初步研究，表明林恩不能正常工作的人谁已被收入急诊病房与生命威胁哮喘。在这项研究中，我们将详细研究林恩在哮喘和过敏中的作用，我们打算确定导致林恩缺陷小鼠哮喘的途径。我们还将研究我们的假设，即林恩活动可能减少或失调的哮喘和过敏患者。这项研究应该会导致更好的预测严重哮喘的标志物，并改善和具体的治疗。

Asthma is a major health problem in Australia affecting over 10% of the population at any time, and more than 25% of the population at one stage in their lives. Although the public perception is that asthma treatments have improved management of the disease, more than 700 people die from severe asthma each year and hospitalisation from exacerbation (sudden worsening) is one of the most costly components of the health care burden in Australia and most developed countries. Currently there are no molecular markers that can predict who will get severe asthma and there are no specific treatments to reverse severe exacerbations. This project will use advanced molecular biology methods to examine whether a molecule called Lyn may be important. The Lyn tyrosine kinase is a member of a family of genes that participate in transmitting information across the cell membrane. This enzyme is expressed in blood cells, and is involved in mechanisms pertaining to infection, immunity and allergic responses. To further our understanding of the role of this enzyme in the context of the whole animal, we have generated mice that are unable to make Lyn protein (Lyn-deficient mice). In animal models of asthma we know that if Lyn is not functioning, severe and persistent asthma develops. We have also made preliminary studies that suggest that Lyn does not work properly in people who have been admitted to the emergency ward with life threatenting asthma. In this study we will examine in detail the role that Lyn plays in asthma and allergy, and we intend to identify the pathways that give rise to asthma in Lyn-deficient mice. We will also investigate our hypothesis that Lyn activity may be reduced or disregulated in patients with asthma and allergy. This research should lead to better predictive markers for severe asthma and also to improved and specific treatments.