Biology of Parasitism
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Parasitism relies on the ability of an organism to exploit its host. Trypanosoma brucei is a unicellular parasite responsible for a fatal disease in humans (sleeping sickness), and for a chronic disease in cattle (nagana) in Sub-Saharan Africa. We are interested in understanding the cellular and molecular mechanisms employed by T. brucei to be an effective parasite. Our group has three main interests:
TISSUE TROPISM - We recently demonstrated that the adipose tissue is a major parasite reservoir during a mouse infection and that parasites functionally adapt to the tissue (1). These unexpected observations raised many questions: how do parasites move between tissues? What is the selective advantage to accumulate in this tissue? Are parasites equally susceptible to drug treatment? How do parasites enter/exit the tissues? What is the extravascular contribution to the dynamics of parasite transmission?
CIRCADIAN RHYTHM – We showed that Trypanosomes have a circadian clock that control their metabolism (2). What are the molecular components and mechanisms of this circadian clock? How does it control metabolism? What is the impact in parasite virulence and disease outcome? We also showed that Trypanosomes alter the circadian rhythm of the host (3). How is this interaction mediated? Who benefits most from these changes? The host or the parasite?
ANTIGENIC VARIATION – A long standing interest of our group is to understand the mechanisms that govern antigenic variation, a process that allows trypanosomes to escape the host immune response (4). We are currently interested in understanding the importance that non-coding RNAs and epigenetic modifications in the regulation of genes underlying antigenic variation.
Our lab has been awarded an ERC consolidator grant in 2017. Previous grants were from HHMI, EMBO, FCT and Gulbenkian.
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1) Trindade, S. et al. (2016). Trypanosoma brucei Parasites Occupy and Functionally Adapt to the Adipose Tissue in Mice. Cell Host Microbe 19, 837-848. (2) Rijo-Ferreira, F. et al. (2017). Trypanosoma brucei metabolism is under circadian control. Nat Microbiol 2, 17032. (3) Rijo-Ferreira, F. et al. (2018). Sleeping sickness is a circadian disorder. Nat Commun 9, 62. (4) Aresta-Branco, F. et al. (2016). A transcription-independent epigenetic mechanism is associated with antigenic switching in Trypanosoma brucei. Nucleic Acids Res 44, 3131-3146.
Ana Raquel Pereira
Senior Postdoctoral Researcherfguegan@medicina.ulisboa.pt
Lara López Escobar
Mariana de Niz
Senior Postdoctoral Researcherstrindade@medicina.ulisboa.pt
Sara Silva Pereira
- Molecular mecanisms of gene expression
- Biology of extra-vascular parasites
- Circadian rhythm of parasites and host
Ongoing Research Projects
2019/2023 Cell2Cell: What makes a successful pathogen? Understanding the impact of cell-to-cell heterogeneity in chromatin structure on infection and adaptation. Coordinator Luísa Figueiredo. Funding Agency: European Commission.
2019/2021 TRYPTISSUE: Characterising Trypanosoma tissue tropism: new perspectives for variant surface glycoproteins. Coordinator: Luísa Figueiredo. Funding Agency: European Commission.
2019/2021 HFSP fellowship - Human Frontier Science Program. Coordinator: Mariana De Niz. Funding Agency: Human Frontier Science Program.
2018/2022 FatTryp: Exploring the hidden life of African trypanosomes: parasite fat tropism and implications for disease. Coordinator: Luísa Figueiredo. Funding Agency: European Commission.
2018/2021 FatReservoir: Importância dos Reservatórios de Parasitas Extravasculares em Gado e Modelos Laboratoriais de Ratinhos. Coordinator: Sandra Trindade. Funding Agency: Fundação para a Ciência e a Tecnologia.
2018/2021 Quando a célula hospedeira já não é tão acolhedora...uma quebra de energia ou um aumento da toxicidade? Coordinator: João Rodrigues. Funding Agency: Fundação para a Ciência e a Tecnologia.
2020 "la Caixa" Foundation - Health Research 2020 Award
2012 HHMI International Early Career Scientist (Luísa Figueiredo)
2010 Crioestaminal Award (Luísa Figueiredo)
2002 Award from the American Society for Tropical Medicine & Hygiene, in recognition of scientific excellence in Molecular, Cellular and Immunoparasitology (Luísa Figueiredo)
Aresta-Branco F, Sanches-Vaz M, Bento F, Rodrigues JA, Figueiredo LM (2019). African trypanosomes expressing multiple VSGs are rapidly eliminated by the host immune system. Proceedings of the National Academy of Sciences 116:20725-20735.
Sanches-Vaz M, Temporão A, Luis R, Nunes-Cabaço H, Mendes AM, Goellner S, Carvalho T, Figueiredo LM, Prudêncio M (2019). Trypanosoma brucei infection protects mice against malaria. PLoS Pathogens 15(11):e1008145.
Rijo-Ferreira, F., Carvalho, T., Afonso, C., Sanches-Vaz, M., Costa, R. M., Figueiredo, L. M., and Takahashi, J. S. (2018). Sleeping sickness is a circadian disorder. Nat Commun 9, 62.
McCulloch, R., Cobbold, C. A., Figueiredo, L. M., Jackson, A., Morrison, L. J., Mugnier, M. R., Papavasiliou, N., Schnaufer, A., and Matthews, K. (2017). Emerging challenges in understanding trypanosome antigenic variation. Emerg. Top. Life Sci. 1, 585-592.
Rijo-Ferreira F, Pinto-Neves D, Barbosa-Morais NL, Takahashi J & Figueiredo LM (2017) Metabolism of Trypanosoma brucei is under circadian control. Nat Microbiol., 2:17032.
Smith, T. K., Bringaud, F., Nolan, D. P., and Figueiredo, L. M. (2017). Metabolic reprogramming during the Trypanosoma brucei life cycle. F1000 Research 6, 1-12.
Cicova Z, Dejung M, Skalicky T, Eisenhuth N, Hanselmann S, Morriswood B, Figueiredo LM, Butter F, Janzen CJ. (2016) Two flagellar BAR domain proteins in Trypanosoma brucei with stage-specific regulation. Sci Rep., 6:35826
Tanowitz HB, Scherer PE, Mota MM and Figueiredo LM. (2016) “Adipose tissue: A safe haven for parasites?” Trends Parasitol., 33:276-284.
Trindade S & Rijo-Ferreira F, Carvalho T, Pinto-Neves D, Guegan F, Aresta-Branco F, Bento F, Young SA, Pinto A, Van Den Abbeele J, Ribeiro RM, Dias S, Smith TK, Figueiredo LM. Trypanosoma brucei parasites occupy and functionally adapt to the adipose tissue in mice. Cell Host and Microbe 2016, 19 (6): 837–848
Aresta-Branco F, Pimenta S, Figueiredo LM. A transcription-independent epigenetic mechanism is associated with antigenic switching in Trypanosoma brucei. Nucleic Acids Res 2015 (7): 3131-3146
Pena AC, Pimentel MR, Manso H, Vaz-Drago R, Pinto-Neves D, Aresta-Branco F, Rijo-Ferreira F, Guegan F, Pedro Coelho L, Carmo-Fonseca M, Barbosa-Morais NL, Figueiredo LM (2014) Trypanosoma brucei histone H1 inhibits RNA polymerase I transcription and is important for parasite fitness in vivo. Molecular Microbiology; 93(4):645- 63
Figueiredo LM, Cross GAM, Janzen CJ. (2009) Epigenetics in African trypanosomes. Nat Rev Microbiol; 7: 504-513
Boothroyd CE, Dreesen O, Leonova T, Ly I, Figueiredo LM, Cross GAM, and Papavasiliou FN. (2009) Single endonuclease-generated DNA breaks induce antigenic switching in Trypanosoma brucei Nature; 459: 278-281
Yang X, Figueiredo LM, Espinal A, Okubo E and Li B. (2009) RAP1 Is Essential for Silencing Telomeric Variant Surface Glycoprotein Genes in Trypanosoma brucei. Cell; 137: 99-109
Figueiredo LM, Janzen CJ, Cross GA. (2008) A Histone Methyltransferase Modulates Antigenic Variation in African Trypanosomes. PLoS Biology; 6 (7): e161