The transcriptome of human sleeping sickness

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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.