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Mota, Maria
Lab

Biology & Physiology of Malaria

Despite renewed eradication efforts from the international community, malaria still exerts an enormous disease burden, with nearly half the planet's population at risk of infection. Within the human host, the disease-causing Plasmodium parasites pass through two distinct lifecycle stages, each in a different cellular environment.

During the liver stage, a single Plasmodium sporozoite will invade a hepatocyte, and while sheltered there gives rise to thousands of new parasites, which will go on to initiate the subsequent blood stage of infection. While only 10-20 new parasites will be generated inside an erythrocyte, consecutive cycles of cell lysis and reinfection causing a potent host response, as well as the symptoms of malaria. It is becoming consensual that malaria control or elimination will never be feasible until we gain a better understanding of the complex interactions occurring between its main players: Plasmodium, the causative agent of disease, and its hosts.

Our ongoing work indicates that the web of host-Plasmodium interactions is densely woven, with liver stage-mediated innate immune system activation (Liehl et al., 2014. Nature Medicine), host nutritional status (unpublished), and an antagonistic relationship between the two parasite stages themselves (Portugal et al., 2011. Nature Medicine) all working to modulate the balance between parasite replication and human health. Altering this balance will be required if we aim to efficiently control this deadly parasite.

  • Research Areas

    • Host-Plasmodium interactions, superinfection and co-infections
    • Plasmodium requirements and the role of host factors in the establishment and course of malaria infections
    • The role of host innate immunity in sensing Plasmodium and the mechanisms used by the parasite to evade host´s immune response
    • The role of Plasmodium sensing pathways in the establishment and course of infection
    • The development of a novel paradigm for an anti-malaria vaccine and the search for novel anti-Plasmodium liver stage agents
  • Research Team

    • Ongoing Research Projects

      • 2012/2017 Nutrient sensing by Parasites - European Research Council Starting Grant. Coordinator: Maria M. Mota. 1.500.000 €
      • 2010/2015 Towards the establishment of a permanent European Virtual Institute dedicated to Malaria Research (EVIMalaR) – EU FP7 European Network of Excellence. IMM coordinator: Maria M. Mota, 12.000.000 € (for the entire consortium)
      • 2013/2015 Host-Plasmodium interactions: a tale of sensing and being sensed – FCT (EXCL/IMI-MIC/0056/2012), Coordinator: Maria M. Mota. 331.643 €
      • 2012/2015 Mechanisms of nutrient-sensing by the malaria parasite - FCT (PTDC/SAU-MET/118199/2010), Coordinator: Liliana Mâncio-Silva. 123.410 €
      • 2013/2015 Regulation of host cell metabolism during malaria liver stage – FCT (PTDC/IMI-MIC/1568/2012), Coordinator: Ghislain Cabal. 168.637 €
      • 2013/2015 Liver stage antimalarials that drive sterile immunity - Bill & Melinda Gates Foundation (Grand Challenges in Global Health – Round 10). Coordinator: Kirsten Hanson. 76.260 €
      • 2014/2015 The role of Iron in Plasmodium life cycle and disease – FCT (EXPL/BIM-MET/0753/2013), Coordinator: Daniel Carapau. 50.000 €
      • 2014/2015 Differentially chemically attenuated liver stage parasites to elucidate the determinants of unnatural acquired immunity to Plasmodium – FCT (EXPL/IMI-MIC/0866/2013), Coordinator: Kirsten Hanson. 50.000 €
      • 2014/2015 A chemical proteomics approach to identify the P. falciparum target of the Torins – FCT (EXPL/BBB-BEP/0746/2013), Coordinator: Ana Filipa Cruz. 50.000 €
    • Prizes

      • 2013 Prémio Pessoa - Maria Manuel Mota (Expresso journal, Caixa Geral de Depósitos bank)
      • 2010 1st Poster Prize to Ghislain Cabal (Post-doctoral fellow) at the EMBO conference "At the Joint Edge of Cellular Microbiology and Cell Biology", given by Science magazine
      • 2008 Prémio Amélia da Silva de Mello para as Ciências da Saúde 4ª Edição, "SR_BI plays a dual role in the establishment of malaria liver infection" (Cristina Rodrigues, Miguel Prudêncio e Maria Mota)
      • 2008 ERA-NET PathoGenoMics PhD Award to Cristina Rodrigues - ERA-NET PathoGenoMics
      • 2008 Prémio Mulher Activa 2008 (2º prémio) to Maria M. Mota - Revista Activa
      • 2007 "Seeds of Science" Prize to Maria M. Mota - Ciência Hoje
      • 2007 CESPU International Science Award 2nd edition - Um contributo para o desenvolvimento das ciências e tecnologias da saúde, "SR_BI plays a dual role in the establishment of malaria liver infection" (Cristina Rodrigues, Miguel Prudêncio e Maria Mota).
      • 2007 1st Poster Prize to Cristina D. Rodrigues (PhD student) - Third Annual BioMalPar Conference on Biology and Pathology of the Malaria Parasite (Heidelberg, Germany)
      • 2005 AMI Health Prize to Maria M. Mota - AMI Foundation
      • 2005 Commander Grã-Cruz Ordem do Inf. D. Henrique - Portuguese Presidency
      • 2005 International Research Scholar to Maria M. Mota - Howard Hughes Medical Institute
      • 2004 European Young Investigator Award to Maria M. Mota – European Science Foundation
      • 2003 EMBO Young Investigator Award to Maria M. Mota – EMBO
    • Selected Publications

      • Itoe MA, Sampaio JL, Cabal GG, Real E, Zuzarte-Luis V, March S, Bhatia SN, Frischknecht F, Thiele C, Shevchenko A, Mota MM. (2014) Host cell phosphatidylcholine is a key mediator of malaria parasite survival during liver stage infection. Cell Host Microbe. 16(6):778-86.
      • Liehl P, Zuzarte-Luís V, Chan J, Zillinger T, Baptista F, Carapau D, Konert M, Hanson KK, Carret C, Lassnig C, Müller M, Kalinke U, Saeed M, Chora AF, Golenbock DT, Strobl B, Prudêncio M, Coelho LP, Kappe SH, Superti-Furga G, Pichlmair A, Vigário AM, Rice CM, Fitzgerald KA, Barchet W, Mota MM. (2014) Host-cell sensors for Plasmodium activate innate immunity against liver-stage infection. Nature Medicine. 20(1):47-53.
      • Hanson KK, Ressurreição AS, Buchholz K, Prudêncio M, Herman-Ornelas JD, Rebelo M, Beatty WL, Wirth DF, Hänscheid T, Moreira R, Marti M, Mota MM. (2013) Torins are potent antimalarials that block replenishment of Plasmodium liver stage parasitophorous vacuole membrane proteins. Proc Natl Acad Sci USA. 110(30):E2838-47
      • Portugal S, Carret C, Recker M, Armitage A, Sullivan D, Roy Cindy, Newbold CJ, Drakesmith H, Mota MM. (2011) Host-mediated control of Malaria Superinfection. Nature Medicine. 17(6):732. (Highlighted in Nature Reviews Microbiology; evaluated in F1000 Biology; Commented in EMBO Mol.Med.)
      • Epiphanio S, Campos MG, Pamplona A, Carapau D, Pena AC, Ataíde R, Monteiro CA, Félix N, Costa-Silva A, Marinho CR, Dias S, Mota MM. (2010) VEGF promotes malaria-associated acute lung injury in mice. PLoS Pathog. 6(5):e1000916.
      • Rodrigues CD, Hannus M, Prudêncio M, Martin C, Gonçalves LA, Portugal S, Epiphanio S, Akinc A, Hadwiger P, Jahn-Hofmann K, Röhl I, van Gemert GJ, Franetich JF, Luty AJF, Sauerwein R, Mazier D, Koteliansky V, Vornlocher HP,5 Echeverri CJ, Mota MM. (2008) Host scavenger receptor SR-BI plays a dual role in the establishment of malaria parasite liver infection. Cell Host & Microbe. 4(3):271-82. (comment in Cell Host & Microbe)
      • Epiphanio S, Mikolajczak SA, Gonçalves LA, Pamplona A, Portugal S, Albuquerque S, Goldberg M, Rebelo S, Anderson DG, Akinc A, Vornlocher HP, Kappe SH, Soares MP, Mota MM. (2008) Heme oxygenase-1 is an anti-inflammatory host factor that promotes murine plasmodium liver infection. Cell Host & Microbe. 3(5):331-8. (comment in Nature Reviews Microbiology)
      • Pamplona A, Ferreira A, Balla J, Jeney V, Balla G, Epiphanio S, Chora A, Rodrigues CD, Gregoire IP, Cunha-Rodrigues M, Portugal S, Soares MP, Mota MM. (2007) Heme oxygenase-1 and carbon monoxide suppress the pathogenesis of experimental cerebral malaria. Nature Medicine. 13:703. (comment in Nature Medicine; evaluated in F1000 Biology and F1000 Medicine)

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