Maria Mota Lab
Biology & Physiology of Malaria
Maria Mota Lab
Biology & Physiology of Malaria
Understanding Malaria at Its Core
Malaria continues to kill a child every minute. At the heart of this disease is Plasmodium, a complex parasite that has co-evolved with humans for millennia. Our lab investigates the biological intricacies that allow Plasmodium to thrive—particularly its remarkable ability to replicate within the liver and the pathways that lead to severe disease. Despite over a century of research, malaria eradication remains elusive. By asking bold, fundamental questions—Why do people die of malaria? What makes the liver uniquely permissive to infection?—our team aims to generate breakthrough discoveries that shift paradigms and accelerate the fight against this devastating disease.
Funders
Decoding the Host–Plasmodium Dialogue
Our lab focuses on unraveling the core mechanisms of malaria pathogenesis by studying how Plasmodium interacts with its host at the cellular, tissue, and systemic levels.
Key discoveries from our group have shown that:
• The liver stage of Plasmodium infection triggers a type I interferon response, challenging the view that it is immunologically silent (Liehl et al., 2014, Nat Med).
• Parasite survival depends on host-pathogen interplay, with parasite proteins such as UIS3 and UIS4 hijacking host autophagy and cytoskeletal defenses (Real et al., 2018, Nat Microbiol; M’Bana et al., 2022, iScience).
• Host nutritional status and iron metabolism profoundly influence infection outcomes, linking dietary habits to malaria progression (Mancio-Silva et al., 2017, Nature).
• The liver’s unique metabolic landscape enables exceptional parasite replication, raising questions about how this impacts disease severity and genetic diversity (Afriat et al., 2022, Nature).
• Host microbiota is an unexpected third player influencing malaria pathology (Mukherjee et al., 2022, Nat Commun).
With a blend of molecular biology, immunology, and systems-level approaches, we are building a holistic picture of malaria – one that connects parasite strategies, host responses, and environmental influences to infection and disease outcome.
2023/2028: Plasmodium Liver Stage Schizogony: High Replication and Genetic Diversity. Coordinator: Maria Mota. Funding Agency: European Commission.
2023/2026: Genetic Variability in Plasmodium Liver Stage Schizogony. Coordinator: Maria Mota. Funding Agency: “la Caixa” Foundation.
Bento I, Parrington BA, Pascual R, Goldberg AS, Wang E, Liu H, Borrmann H, Zelle M, Coburn N, Takahashi JS, Elias JE, Mota MM, Rijo-Ferreira F (2025). Parasite and vector circadian clocks mediate efficient malaria transmission. Nat Microbiol. Mar 31. Epub ahead of print.
Marreiros IM, Marques S, Parreira A, Mastrodomenico V, Mounce BC, Harris CT, Kafsack BF, Billker O, Zuzarte-Luís V, Mota MM (2023). A non-canonical sensing pathway mediates Plasmodium adaptation to amino acid deficiency. Comm Biology. 6(1):205.
Chora ÂF, Marques S, Gonçalves JL, Lima P, Gomes da Costa D, Fernandez-Ruiz D, Marreiros MI, Ruivo P, Carvalho T, Ribeiro RM, Serre K, Heath WR, Silva-Santos B, Tate AT, Mota MM (2023). Interplay between liver and blood stages of Plasmodium infection dictates malaria severity via γδ T cells and IL-17-promoted stress erythropoiesis. Immunity. 56(3):592-605.e8.
Afriat A, Zuzarte-Luís V, Bahar Halpern K, Buchauer L, Marques S, Chora ÂF, Lahree A, Amit I, Mota MM, Itzkovitz S (2022). A spatiotemporally resolved single-cell atlas of the Plasmodium liver stage. Nature. 611(7936):563-569.
Mukherjee D, Chora ÂF, Lone JC, Ramiro RS, Blankenhaus B, Serre K, Ramirez M, Gordo I, Veldhoen M, Varga-Weisz P, Mota MM (2022). Host lung microbiota promotes malaria-associated acute respiratory distress syndrome. Nat Comm. 13(1):3747.
M’Bana V, Lahree A, Marques S, Slavic K, Mota MM (2022). Plasmodium parasitophorous vacuole membrane-resident protein UIS4 manipulates host cell actin to avoid parasite elimination. iScience. 25(5):104281.
Real E, Rodrigues L, Cabal GG, Enguita FJ, Mancio-Silva L, Mello-Vieira J, Beatty W, Vera IM, Zuzarte-Luís V, Figueira TN, Mair GR, Mota MM (2018). Plasmodium UIS3 sequesters host LC3 to avoid elimination by autophagy in hepatocytes. Nat Microbiol. 3(1):17-25.
Zuzarte-Luis V, Mello-Vieira J, Marreiros IM, Liehl P, Chora AF, Carret C, Carvalho T and Mota MM (2017). Dietary alterations modulate susceptibility to Plasmodium infection. Nat Microbiol. 2(12):1600-1607.
Mancio-Silva L, Slavic K, Grilo Ruivo MT, Grosso AR, Modrzynska KK, Vera IM, Baena-Gonzalez E, Tewari R, Llinás M, Billker O, Mota MM (2017). Nutrient sensing modulates malaria parasite virulence. Nature. 547(7662):213-216.
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. Nat Med. 20(1):47-53.
International Recognitions:
2018: Sanofi Institut Pasteur Prize – Maria Mota
2016: EMBO Member – Maria Mota
2005: HHMI International Research Scholar – Maria Mota
2004: European Young Investigator Award – Maria Mota
2003: EMBO Young Investigator Award – Maria Mota
National Distinctions:
2017: Pfizer Award for Basic Research – SCML & Pfizer Labs
2017: L’Oréal Portugal Medal for Women in Science – Inês Bento
2013: Prémio Pessoa – Maria Mota
2005: Commander, Grã-Cruz Ordem do Infante D. Henrique – Portuguese Presidency – Maria Mota
Team
On the Verge of Discovery