Biology & Physiology of Malaria
Disease burden is disproportionally distributed around the globe. A direct contributor to such asymmetry is malaria – more than 200 million new infections and 400 thousand deaths still occur every year. Despite this unacceptably high health, economic and social burden, the factors that dictate the onset of severe disease and outcome of infection remain poorly understood, which significantly impairs the combat to this deadly disease.
Our overall goal has been and will continue to be towards the elucidation of the most fundamental and conceptually innovative questions of Host-Plasmodium interactions.
With previous work, we have challenged the widespread assumption that Plasmodium can infect and replicate inside hepatocytes undetected by showing: that Plasmodium activates a type I IFN response in the liver (Liehl et al., 2014. Nature Medicine) and that Plasmodium has a molecule that resides in the membrane that separates the parasite from the hepatocyte cytoplasm that interacts with the host autophagy machinery blocking it (Real et al. 2018. Nature Microbiology). We have also identified a host factor mediating the antagonistic effect of one of the parasite’s stage over the other (Portugal et al., 2011. Nature Medicine). That finding paved the way to elucidate how Plasmodium regulates iron levels in order to survive (Slavic et al., 2016. Nature Communications) and ushered the concept that nutrient availability and dietary habits strongly impact the establishment and course of a malaria infection by interfering with both host and parasite pathways during different stages of infection (Mancio-Silva et al., 2017. Nature; Zuzarte-Luis et al., 2017. Nature Microbiology).
Our ongoing work indicates that the web of host-Plasmodium interactions is indeed densely woven, with liver stage and the blood stage interacting towards pathology and disease severity. Moreover, we have identified a third party determining disease – host microbiota.
We are also continuing to pursue a lasting question – What is so special about the liver? Our data indicates that the liver special metabolism is the key to modulate the ability of Plasmodium species that infect mammals to achieve extraordinary rates of replication to generate tens of thousands of erythrocyte-infectious merozoites.
Research Team
Research Areas
- Liver Metabolism determining parasite replication.
- Host-Plasmodium-Microbiota interactions.
- Liver and blood stages of infection cross-talking.
- Parasite nutrient sensing and adaptation.
Ongoing Research Projects
2018/2021 Plasmodium Exploitation of Liver-specific Methionine Metabolism. Coordinator: Maria M. Mota. Funding Agency: "la Caixa" Foundation.
2018/2021 Hepatic metabolism driving Plasmodium replication. Coordinator: Maria M. Mota. Funding Agency: Fundação para a Ciência e a Tecnologia.
2018/2021 Plasmodium cross-stage interplay modulates Severe Malaria pathology. Coordinator: Ângelo Ferreira-Chora. Funding Agency: Fundação para a Ciência e a Tecnologia.
2018/2021 Plasmodium Iron regulatory Network: the need to sense, acquire and detoxify. Coordinator: Vanessa Zuzarte-Luís. Funding Agency: Fundação para a Ciência e a Tecnologia.
2018/2021 Sanofi - Institut Pasteur Awards 2018. Coordinator: Maria Mota. Funding Agency: Institut Pasteur.
2018/2021 Prémio Lóreal. Coordinator: Inês Bento. Funding Agency: L’oréal Paris.
Awards
- International
2018 - Maria Mota, Sanofi Institut Pasteur Prize.
2018 - Sara Baptista. Honor - Ambassador Next Einstein Forum for Cabo Verde.
2018 - Debanjan Mukherjee. Honor of scientific excellence in the field of Cellular, Molecular and Immunoparasitology. 67th Annual Meeting American Society for Tropical Medicine and Hygiene New Orleans, Louisiana, U.S.A.
2018 - Debanjan Mukherjee. Best oral communication Award. Annual Molecular Parasitology Meeting, MBL, Woods Hole, Massachusetts, U.S.A.
2016 - Maria Mota, EMBO Member, European Molecular Biology Organization.
2005 - Maria Mota, International Research Scholar, Howard Hughes Medical Institute, U.S.A.
2004 - Maria Mota, European Young Investigator Award, European Science Foundation.
2003 - Maria Mota, EMBO Young Investigator Award, European Molecular Biology Organization.
- National (a selection)
2017 - Maria Mota, Pfizer Award Basic Research, SCML & Pfizer Laboratories.
2017 - Inês Bento, “Medalhas de Honra L’Oréal Portugal para as Mulheres na Ciência”.
2013 - Maria Mota, Prémio Pessoa.
2005 - Maria Mota, Commander, Grã-Cruz Ordem do Infante D. Henrique, Portuguese Presidency.
Others:
2018 - Debanjan Mukherjee, Best oral communication Award. XII CAMLPhD Students Meeting at Faculdade de Medicina de Lisboa.
2018 - Aparajita Lahree, Best poster communication Award, Bioengineering Systems. MIT-Portugal Annual Conference, Lisbon, Portugal.
2017 - Debanjan Mukherjee, 3rd year Best Poster award, XI CAML PhD students Meeting iMM, Faculdade de Medicina de Lisboa.
2009 - Maria Mota, Prémio Rotary Investigação-Ciência, Rotary Club.
2009 - Maria Mota, Prémio Saúde, Correio da Manhã.
2008 - Maria Mota, Mello Award, Mello Foundation.
2008 - Maria Mota, Mulher Activa 2008 (2º prémio), Revista Activa.
2007 - Maria Mota, Seeds of Science, Ciência Hoje.
2007 - Maria Mota, CESPU Award, CESPU Foundation.
2005 - Maria Mota, AMI Health Prize, AMI Foundation.
2004 - Maria Mota, Prémio de Mérito e Talento, SIC.
Selected Publications
Mello-Vieira J, Enguita FJ, de Koning-Ward TF, Zuzarte-Luís V, Mota MM (2020). Plasmodium translocon component EXP2 facilitates hepatocyte invasion. Nature Communications 11(1):5654.
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. Nature Microbiology. 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. Nature Microbiology. 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. (evaluated in F1000 Biology).
Slavic K, Krishna S, Lahree A, Bouyer G, Hanson KK, Vera I, Pittman JK, Staines HM, Mota MM. 2016. A vacuolar iron-transporter homologue acts as a detoxifier in Plasmodium. Nature Communications 7:10403.
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.
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).
Useful Links
- Group Leader at iMM since 2005
- Executive Director at iMM since 2014
- Sanofi - Institut Pasteur -International Mid Career Award in 2018
- EMBO member since 2016
- Professor, FMUL, University of Lisbon since 2005
- International Research Scholar Howard Hughes Medical Institute (2005-2010)
- Principal Investigator at Instituto Gulbenkian de Ciência (2002-2005)
- European Science Foundation Young Investigator (2004-2009)
- Postdoctoral research at New York University Medical Center (1999-2001)
- PhD in Molecular Parasitology at University College London (1998)