A high throughput model of Cryptococcus Infection and Cell Biology In Vivo for identifying host and pathogen disease determinants and new therapeutics

我感兴趣的是我们的免疫系统是如何和不能去除可能导致疾病的微生物的。当一个人感染了艾滋病毒（导致艾滋病的病毒）时，免疫系统就不能正常工作了。其他例子包括癌症、器官移植期间和之后以及类风湿关节炎治疗期间。当免疫系统不能正常工作时，我们可能会因为一种通常不会引起重大问题的微生物而生病。其中一种微生物是真菌隐球菌。隐球菌感染在免疫系统正常的人群中是非常罕见的，但在患有严重艾滋病毒感染的个体中，隐球菌感染更为常见，而且非常严重。艾滋病的流行导致一大群人对隐球菌易感，据估计，每年有多达100万例病例和60万人死于隐球菌。引起人类疾病的真菌并不常见，而引起严重疾病的真菌则非常罕见。导致人类严重疾病的真菌很难治疗，因为我们现有的药物通常对我们也非常有害。除了在免疫系统不正常的人身上引起严重疾病的隐球菌外，还发现了第二种隐球菌，它可以在免疫系统明显正常的人身上引起疾病。第二种类型主要在赤道附近发现，但在该地区以外的数量也在增加。我的研究是试图了解为什么隐球菌会导致疾病的不同领域，这样我们就可以找到更好的治疗方法。我在研究中提出的问题是：免疫系统发生了什么变化，这意味着我们严重感染了隐球菌？是什么使某些隐球菌感染更严重（毒性）？有没有什么新药可以用来改善我们治疗隐球菌的方法？我将使用我在斑马鱼身上开发的隐球菌感染模型来探索这些问题。斑马鱼的免疫系统与人类相似，我可以观察活体动物的免疫细胞，看看感染过程中会发生什么。我还打算用这个模型来测试可能的新药。我的希望是，通过这项研究，我们将对隐球菌如何以及为什么引起疾病有更深入的了解，这将导致新的治疗方法。

I am interested in how our immune system is and is not able to remove micro-organisms that can cause disease. An example of where the immune system is not able to work properly is when a person is infected with HIV (the virus that causes AIDS). Other examples include cancer, during and after organ transplantation and during treatment for rheumatoid arthritis. When the immune system is not working properly we may become ill with a micro-organism that normally would not cause a significant problem. One such micro-organism is the fungus Cryptococcus.Infections with Cryptococcus are very unusual in those with a normal immune system but in individuals with, for example, severe HIV infection, Cryptococcus is much more common and very serious. The AIDS epidemic has resulted in a large group of people who are susceptible to Cryptococcus and it has been estimated that there are as many as 1 million cases and 600, 000 deaths due to Cryptococcus each year. Fungi that cause disease in humans are uncommon and those that cause serious disease are very rare. Fungi that cause serious disease in humans are difficult to treat because the drugs we have are often quite harmful to us as well.As well as the Cryptococcus that causes serious disease in those with immune systems that are not working, there is a second type that has been found to cause disease in people who have apparently normal immune systems. This second type is mainly found around the equator but there have been increasing numbers outside this area.My research is trying to understand these different areas of why Cryptococcus causes disease so that we can find better treatments. The questions I am asking in my research are: What happens to the immune system that means we are seriously infected with Cryptococcus? What makes infection with some types of Cryptococcus more severe (virulent)? Are there any new drugs that we can use to improve the way we treat Cryptococcus?I will explore these questions using a model of Cryptococcus infection I have developed in the zebrafish. The zebrafish has a similar immune system to our own and I can observe the immune cells of living animals and see what happens during the infection. I am also going to use this model to test possible new drugs. My hope is that through this research we will have a greater understanding of how and why Cryptococcus causes disease and that this will lead to new treatments.