Publicação
Longitudinal analysis of adipocytes and liver gene expression during T. brucei infection
| Resumo: | Trypanosoma brucei is an extracellular protozoan that causes Human African Trypanosomiasis (HAT) and Animal African Trypanosomiasis (AAT), also known as sleeping sickness and nagana respectively. This parasite is transmitted by tsetse flies, but it is inside a mammalian host that it completes its life cycle. Recently, the adipose tissue was found to be a significant reservoir for T. brucei, triggering a functional adaptation of the parasite to the tissue environment. Furthermore, during infection, most hosts experience weight loss and adipocytes lose their stored lipid content. With a host-oriented view, the goal of this project was to characterize transcriptome changes that occur throughout the infection process and identify key biological pathways for future genetic manipulation. To accomplish this goal, RNA sequencing was performed on adipocyte and liver tissue samples at different timepoints of infection. Both tissues are metabolically tied and would provide a view of the systemic changes that happen in the host during infection. This study followed a typical transcriptomic analysis methodological approach which resulted in sets of differentially expressed genes that were subsequently associated to their functionality. The comparison of experimental conditions revealed that, although there was a big change between non-infected and infected timepoints, few transcriptomic changes were identified among different timepoints of infection, suggesting that the first days after infection are when the host alters its gene expression in response to the disease. We observed that, while the adipose tissue suffers a decrease in its extracellular matrix organization, the liver has a decrease in fatty acid metabolism, with both tissues experiencing a strong immune response against the parasite. Overall, this work established the impact of T. brucei on gene expression of two key organs throughout infection, providing a better understanding of the disease and possible new ways to counteract it. |
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| Autores principais: | Colaço, João Francisco Parraga Ribeiro |
| Assunto: | Trypanosoma brucei Tecido adiposo Fígado RNA-Seq Transcriptoma Teses de mestrado - 2020 |
| Ano: | 2020 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório da Universidade de Lisboa |
| Resumo: | Trypanosoma brucei is an extracellular protozoan that causes Human African Trypanosomiasis (HAT) and Animal African Trypanosomiasis (AAT), also known as sleeping sickness and nagana respectively. This parasite is transmitted by tsetse flies, but it is inside a mammalian host that it completes its life cycle. Recently, the adipose tissue was found to be a significant reservoir for T. brucei, triggering a functional adaptation of the parasite to the tissue environment. Furthermore, during infection, most hosts experience weight loss and adipocytes lose their stored lipid content. With a host-oriented view, the goal of this project was to characterize transcriptome changes that occur throughout the infection process and identify key biological pathways for future genetic manipulation. To accomplish this goal, RNA sequencing was performed on adipocyte and liver tissue samples at different timepoints of infection. Both tissues are metabolically tied and would provide a view of the systemic changes that happen in the host during infection. This study followed a typical transcriptomic analysis methodological approach which resulted in sets of differentially expressed genes that were subsequently associated to their functionality. The comparison of experimental conditions revealed that, although there was a big change between non-infected and infected timepoints, few transcriptomic changes were identified among different timepoints of infection, suggesting that the first days after infection are when the host alters its gene expression in response to the disease. We observed that, while the adipose tissue suffers a decrease in its extracellular matrix organization, the liver has a decrease in fatty acid metabolism, with both tissues experiencing a strong immune response against the parasite. Overall, this work established the impact of T. brucei on gene expression of two key organs throughout infection, providing a better understanding of the disease and possible new ways to counteract it. |
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