The transcriptome of human sleeping sickness

人类锥虫病在非洲很普遍。几乎没有可用的化学疗法，也缺乏现代诊断方法。该项目的结果将为人类锥虫相互作用提供新的见解，并为新的诊断工具提供基础。几乎所有关于锥虫代谢和基因表达的实验都是用培养的寄生虫进行的，结果被用来确定化疗的靶点。我们在这里的目的是寻找人类血液中的锥虫，脑脊液中的锥虫和培养的锥虫之间的差异。使用高通量测序，我们将直接从昏睡病患者身上提取锥虫的转录组。使用相同的人类样本，我们将比较昏睡病患者和对照组的白细胞转录组。结果将与炎症介质和细胞类型的测量结果相关。我们还将使用免疫沉淀和质谱法来识别患者抗体特异性识别的锥虫抗原：这些抗原可以形成简单诊断的基础。该项目将在乌干达建立尖端的生物信息学和样品制备方法，可用于许多传染病的研究。

Human trypanosomiasis is widespread in Africa. Few chemotherapies are available and modern diagnostic methods are lacking. The results of this project will provide new insights into the humantrypanosome interaction, and should provide a basis for new diagnostic tools. Nearly all experiments on trypanosome metabolism and gene expression have been done with cultured parasites, and the results are used to identify targets for chemotherapy. We here aim to look for differences between trypanosomes in human blood, trypanosomes in cerebrospinal fluid, and cultured trypanosomes. Using high throughput sequencing, we will characterise the transcriptomes of trypanosomes taken directly from sleeping sickness patients. Using the same human samples, we will compare the transcriptomes of leukocytes from sleeping sickness patients and controls. Results will be correlated with measurements of inflammatory mediators and cell types. We will also use immunoprecipitation and mass spectrometry to identify trypanosome antigens that are specifically recognised by patient antibodies: such antigens could form the basis of a simple diagnostic. The project will establish, in Uganda, cutting-edge bioinformatic and sample-preparation methods which can be used in the study of many infectious diseases.