Evaluating the importance of autophagy/xenophagy in protecting the intestinal epithelium in Crohn s Disease

炎症性肠病(IBD)是西方世界常见的终生疾病。这两种疾病的常见症状包括腹痛、体重减轻和腹泻。炎症性肠病主要有两种类型：克罗恩-S病(CD)和溃疡性结肠炎(UC)。这些疾病的原因尚不确定，但现在很明显，每种情况都受到一些遗传风险因素和环境因素的影响。这些因素包括肠道细菌的存在和吸烟习惯。近年来，在识别与克罗恩-S病有关的几个新的遗传危险因素方面取得了很大进展。最近发现的两个基因参与了一种称为自噬的过程，细胞通过这种机制保存或回收特定的蛋白质，以保持自己在饥饿条件下或特定环境压力下的生存。有一些证据表明，自噬也可能与维持健康的肠道有关，移除或杀死？不好？细菌和放任？好吗？细菌在那里生活。改变自噬途径的调节可能会打破这种微妙的平衡，或者允许？好的？细菌从肠道细胞产生不必要的反应，导致炎症。在一系列的实验室实验中，我们的目标是研究这一途径，并阐明CD患者的功能是如何改变的，以及不同环境应激源和基因改变的影响。结果将表明这一途径是否与CD的发生或发展有关，也可能表明所涉及的分子途径，可能导致新的药物治疗的发展。

The inflammatory bowel diseases (IBD) are disabling life-long illnesses which are common in the Western world. Typical symptoms common to both illnesses include abdominal pain, weight loss, and diarrhoea. There are two main types of inflammatory bowel disease: Crohn?s disease (CD) and ulcerative colitis (UC). The cause of these illnesses is not certain, but it is now very clear that each condition is influenced by a number of genetic risk factors as well as environmental factors. These include the presence of bacteria in the bowel and smoking habit. Recently, great progress has been made in identifying several new genetic risk factors involved in Crohn?s disease. Two of the most recently identified genes are involved in a process called autophagy, a mechanism by which cells conserve or recycle specific proteins to keep themselves alive in conditions of starvation, or under specific environmental ?stressors?. There is some evidence that autophagy might also be involved in the maintenance of a healthy gut, removing or killing ?bad? bacteria and allowing ?good? bacteria to live there. Changes in the regulation of the autophagy pathway might upset this delicate balance or allow ?good? bacteria to produce unwanted responses from the gut cells, leading to inflammation. In a series of laboratory experiments, we aim to investigate this pathway and to clarify how function is changed in CD patients and the effect of different environmental ?stressors?, and of genetic alterations. Results will indicate whether this pathway is involved in the cause or development of CD and may also indicate the molecular pathways involved which could potentially lead to the development of new drug therapy.