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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 Nature Medicine), host nutritional status (unpublished), and an antagonistic relationship between the two parasite stages themselves (Portugal et al., 2011.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 Team

Ana Parreira
Lab Technician
anaparreira@medicina.ulisboa.pt

Aparajita Lahree
PhD Student
aparajitalahree@medicina.ulisboa.pt

Camila Mariano
MSc Student
camilamariano@medicina.uilisboa.pt

Catarina Pedro
MSc Student
catarina.pedro@medicina.ulisboa.pt

Cristina Arias
Senior Post-Doctoral Researcher
cristina.arias@medicina.ulisboa.pt

Debanjan Mukherjee
PhD Student
debanjan.mukherjee@medicina.ulisboa.pt

Inês Bento
Senior Post-Doctoral Researcher
ibento@medicina.ulisboa.pt

Inês Marreiros
PhD Student
maria.marreiros@medicina.ulisboa.pt

Joana Gonçalves
PhD Student
joanagoncalves@medicina.ulisboa.pt

João Vieira
PhD Student
joaotvieira@medicina.ulisboa.pt

Margarida Vigário
Senior Post-Doctoral Researcher
avigario@medicina.ulisboa.pt

Sara Baptista
PhD Student
ssbaptista@medicina.ulisboa.pt

Sofia Guia Marques
Lab Manager
smarques@medicina.ulisboa.pt

Sonali Setua
Post-Doctoral Researcher
sonali.setua@medicina.ulisboa.pt

Soraia Marques Caetano
Post-Doctoral Researcher
soraia.caetano@medicina.ulisboa.pt

Sónia Pereira
PhD Student
s.pereira@medicina.ulisboa.pt

Vanessa Zuzarte Luis
Senior Post-Doctoral Researcher
vluis@medicina.ulisboa.pt

Viriato M`Bana
PhD Student
viriatombana@medicina.ulisboa.pt

Yash Pandya
Post-Doctoral Researcher
yash.pandya@medicina.ulisboa.pt

Ângelo Ferreira Chora
Senior Post-Doctoral Researcher
angelochora@medicina.ulisboa.pt

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

Ongoing Research Projects

2018-2021 Plasmodium Exploitation of Liver-specific Methionine Metabolism. Funding Agency: "la Caixa" Foundation. Coordinator: Maria M. Mota.

2018-2021 Hepatic metabolism driving Plasmodium replication. Funding Agency: Fundação para a Ciência e a Tecnologia. Coordinator: Maria M. Mota.

2018-2021 Plasmodium cross-stage interplay modulates Severe Malaria pathology. Funding Agency: Fundação para a Ciência e a Tecnologia. Coordinator: Ângelo Ferreira-Chora.

2018-2021 Plasmodium Iron regulatory Network: the need to sense, acquire and detoxify. Funding Agency: Fundação para a Ciência e a Tecnologia. Coordinator: Vanessa Zuzarte-Luís.

2016-2019 Evasion of host-mediated autophagy: mechanisms of Plasmodium survival in the liver-stage infection. Funding Agency: Fundação para a Ciência e a Tecnologia. Coordinator: Maria M. Mota.

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

• 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).

group leader :
Maria Mota