Université de Strasbourg

João Marques

Biography

Department of Biochemistry and Immunology, Federal University of Minas Gerais, Brazil & USIAS Fellow in the research unit for Innate Immune Response in Insect Models (M3I), University of Strasbourg & CNRS

João Marques, USIAS Fellow 2019

Dr. João Trindade Marques received his PhD in 2002 from the Brazilian Federal University of Minas Gerais, during which his work focused on the interaction between viruses and host immune responses. Dr. Marques was subsequently a post-doctoral fellow at Cleveland Clinic (USA) in the laboratory of Professor Bryan R. G. Williams, who is known for his discovery of the protein kinase R (PKR), a double stranded (dsRNA)-activated kinase. During this period, he worked on dsRNA recognition and signaling pathways activated by viruses during infection in mammals. The use of RNA interference in research and therapeutics was a growing field and Dr. Marques worked extensively in ways to minimise non-specific effects of synthetic double-stranded RNAs on mammalian cells. In 2006, his interest in the area of RNA interference led him to join the laboratory of Professor Richard Carthew at Northwestern University (USA). There, he utilised the Drosophila melanogaster model to characterise the mechanism of RNA interference, especially in response to viral infection.

In 2010, João Marques joined the Department of Biochemistry and Immunology at the Federal University of Minas Gerais, and started a research group focused on insect antiviral immunity. His main area of interest is on antiviral immune responses in insect vectors such as Aedes aegypti mosquitoes that transmit human viruses such as Dengue and Zika. During his career, DR. Marques has published in important journals such as Nature Biotechnology, Nature Structural and Molecular Biology, Nature Microbiology and Nucleic Acids Research, among others. For his work, he received two prizes from the International Society of Interferon and Cytokine Research: the Milstein Young Investigator award in 2005 and the Boltzmann award in 2008. He was also elected affiliate member of the Brazilian Academy of Sciences in 2010 and the World Academy of Sciences (TWAS) in 2013.

Project - The molecular basis of natural antiviral resistance against Dengue and Zika viruses in Aedes aegypti mosquitoes

01/12/2019 - 31/01/2022

Arthropod-borne viruses (arboviruses) transmitted by mosquitoes, such as Dengue and Zika, pose a great threat to human health worldwide. Incidence of Dengue alone has increased ~30 times over the last 50 years and is currently at 400 million new infections every year. We lack effective vaccines and treatment for mosquito borne viruses and most public health measures are based on vector population control. Although mosquitoes are central to the transmission of these viruses, the effectiveness and impact of vector control is unclear. In this scenario, mosquitoes have natural antiviral resistance that could be explored to prevent transmission of arboviruses.

The major goal of this project is to characterise mechanisms required for resistance to Dengue and Zika viruses in mosquitoes. Although there have been major breakthroughs in understanding resistance against the malaria parasite in Anopheles mosquitoes and several major discoveries on the mechanisms of antiviral defence in the fruit fly Drosophila melanogaster, studies in Aedes mosquitoes have lagged behind. Studies describing the mechanisms involved in the control of arbovirus infection in Aedes mosquitoes have been mostly based on three strategies: (i) mechanisms previously described in other organisms such as the fruit fly Drosophila melanogaster; (ii) pathways that are transcriptionally regulated by infection; and (iii) unbiased screens using cell lines. These have led to important discoveries but were limited by analyses that were either biased (conserved mechanisms and pathways that require regulation at the transcriptional level) or lacked the in vivo context (studies in cell lines). Thus, we still lack basic understanding about molecular mechanisms of mosquito resistance to viral infection.

Within this project, Dr Marques proposes a unique and robust approach that goes beyond these limitations by analysing mechanisms that mediate natural antiviral resistance in adult mosquitoes independent on conservation or transcriptional regulation. Preliminary results suggest that complex I of the respiratory chain regulates resistance to the Dengue virus, which is uncharted territory in terms of antiviral mechanisms. Thus, the team's unique approach has great potential to lead to truly novel discoveries that may help provide solutions to the growing problem of mosquito borne viruses. In the long term, clear understanding of antiviral resistance is a big step towards strategies that can modulate the transmission of arboviruses.

During his Fellowship, João Marques will be hosted by Professor Jean-Luc Imler in the Innate Immune Response in Insect Models (M3I) research unit at the University of Strasbourg.

Post-doc biography - Flávia Viana Ferreira

Innate Immune Response in Insect Models (M3I), University of Strasbourg & CNRS

Flávia Viana Ferreira

Flávia Viana Ferreira  received her master’s degree in 2011 from the Brazilian Federal University of Minas Gerais, under Dr Erna Kroon’s supervision. Her work was mainly on Dengue virus detection in mosquito Aedes sp. caught in Belo Horizonte city, Brazil. Subsequently, her main area of interest focused on antiviral immune responses in invertebrate vectors. In 2015, she received her PhD from the Federal University of Minas Gerais under Dr João Marques’ supervision, and with the collaboration of Professor Jean-Luc Imler from the University of Strasbourg. In her work, she identified and also characterised the RNA interference pathway in the sandfly Lutzomyia longilpalpis - the vector insect of Leishmania - after it had been infected with Vesicular stomatitis virus (VSV), a rhabdovirus naturally transmitted by this insect.

Flávia Viana Ferreira was subsequently a post-doctoral fellow at the University of São Paulo (USP) in the laboratory of Professor Sirlei Daffre who is known for her works with tick vectors and Rickettsia rickettsii infection - a bacteria that causes Rocky Mountain spotted fever. In this period, she identified and characterised some immune targets that are directly related to the resistance or susceptibility of tick vectors to rickettsia infection. In 2018, her interest in the mosquito Aedes aegypti with human viruses such as Dengue and Zika led her to join the laboratory of Professor João Marques at the Federal University of Minas Gerais. At the University of Strasbourg, she will also work with him on his USIAS project.

During her career, she received three important Brazilian fellowship awards, two bioinformatics projects collaboration awards, and has had articles published in important journals.

Investissements d'Avenir