Université de Strasbourg

João Marques


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 and 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 - Fabien Aubry

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

Fabien Aubry

Fabien Aubry received his PhD in human pathology and infectious diseases in 2014 from Aix-Marseille University (France), under the supervision of Professor Xavier de Lamballerie. During his thesis, he became interested in viruses that are pathogenic to humans and transmitted by arthropods (arboviruses). Throughout these years, he studied the impact of a new mechanism of virus attenuation based on random codon re-encoding on the phenotype and genetic stability of different arboviruses. He also developed a new reverse genetics system to simply and quickly generate wild-type and attenuated infectious viruses.

In 2017, he joined the team of Dr. Louis Lambrechts at the Institut Pasteur in Paris to study the factors promoting the emergence of arboviruses in the human population by focusing more specifically on the interactions between the Aedes aegypti mosquito and the Zika virus. His research enabled the identification of one such factor by showing that Aedes aegypti’s preference for biting humans and it’s range expansion out of Africa have been accompanied by an increase in its intrinsic ability to acquire and transmit the Zika virus, which may have promoted its emergence in the Pacific and the Americas.

In November 2020, he joined the research unit Innate Immune Response in Insect Models (M3I) at the University of Strasbourg to work with Dr. João Trindade Marques on his USIAS project dealing with the molecular mechanisms of Aedes aegypti's natural antiviral resistance to dengue and Zika viruses.

Investissements d'Avenir