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Complementary Expertise

Specialists in mosquito olfaction and immunity launch a cooperative tropical disease network between Brazil and the United Kingdom

Aedes aegypti: from studies on the dengue mosquito’s gut microbiota to plans to create insects whose genes are silenced

CDCAedes aegypti: from studies on the dengue mosquito’s gut microbiota to plans to create insects whose genes are silencedCDC

A workshop planned for July 13-14, 2015 in Botucatu, in inland São Paulo State, will bring together researchers from universities and institutions in the state of São Paulo, a delegation from the University of Keele in the United Kingdom, and probably a representative from the Wellcome Trust, a British foundation that supports biomedical research, to discuss how to broaden scientific collaboration in the area of tropical diseases.  The meeting will take place in Botucatu because it is there that a pioneering partnership was born of this cooperation, between biologists Jayme Souza-Neto of the Institute of Biotechnology (IBTEC) at São Paulo State University (Unesp) and Julien Pelletier of the Center for Applied Entomology and Parasitology at the University of Keele, under the aegis of a cooperation agreement signed by FAPESP and the British university in 2013.  “The objective is that after two days of meetings, we’ll have generated some solid ideas for joint research projects that can be presented to funding agencies in Brazil and the United Kingdom,” says Souza-Neto.

The partnership agreement provides for annual visits by each of the researchers to his partner’s laboratory over the course of three years.  Currently, Souza-Neto is spending three months at Keele, where Pelletier is teaching him how to work with a recently created tool called the CRISPR-Cas9, which makes it possible to silence specific vector genes and has already resulted in the creation of mutant insects through embryo manipulation.  One of Pelletier’s lines of research is to understand how genes linked to the insect’s olfactory system influence their attraction to humans by analyzing the behavior of mutant insects.  He is currently developing colonies of mutant mosquitos of the type that transmit malaria in Africa (Anopheles gambiae) for his functional trials.  At the same time, Souza-Neto is sharing his expertise on the mosquito’s immune response to dengue fever with his colleague, whose experience has been shaped more by vectors like the malaria-causing mosquito.  He will help Pelletier create a system in his laboratory at Keele to infect Aedes aegypti with the virus that causes dengue.  Pelletier will soon depart for Brazil to spend some time there.  “From my personal perspective, cooperation between FAPESP and the University of Keele represents a great opportunity to develop an ambitious research program that combines the expertise found in Brazil and the United Kingdom,” says Pelletier.  “By bringing together two components of vector biology, that of olfaction and immunity, I believe we can make a real contribution to understanding how pathogens are transmitted to human beings.  The network will also benefit from the sharing of technology between my lab in Keele and that of Dr. Souza-Neto in Botucatu,” he says.

Exchange of knowledge
The call for projects under the cooperation agreement between FAPESP and the University of Keele provides for the recruiting of a Brazilian researcher who works in the area of tropical diseases to work in a joint effort with a group at Keele – the duo will serve as pioneers of a broader collaboration in the future.  “The idea was to identify two groups with solid and complimentary research interests,” says Souza-Neto.  His and Pelletier’s names arose precisely because they work in areas that offer great potential for the exchange of expertise.  Born in France, Pelletier has studied the physiology of insects since he graduated from the University of Paris 6.  He completed a PhD in molecular biology at the Institut National de la Recherche Agronomique [National Institute of Agronomy Research] (INRA) in Versailles, working on the characterization of olfactory proteins involved in the antennal reception of pheromone in the silkmoth.  In 2013, after completing a post-doctoral program at the University of California-Davis in the United States and Sveriges Lantbruks Universitet in Sweden, he was invited to work at Keele.

Jayme Souza-Neto was selected by the FAPESP program, Young Investigators in Emerging Centers, also in 2013, after having completed a 3-year post-doctoral program at the Malaria Research Institute of the Johns Hopkins Bloomberg School of Public Health (JHMRI/JHSPH), where he focused his academic work on the immune response of vector mosquitos to pathogens like dengue and Plasmodium.  As a FAPESP Investigator, he returned to Unesp, where he had completed his dissertation on genetics in 2006, to set up a laboratory dedicated to studying the Aedes aegypti mosquito, with a specific focus on the interaction between the mosquito’s gut microbiota and the dengue virus.  The Vector Functional Genomics & Microbiology Laboratory (Vectomics), headed by Souza-Neto, is equipped with instruments that have basic molecular biology applications in chambers in order to grow and infect mosquitos.  He will also be working with a next generation sequencer, Illumina NextSeq, which was recently acquired by IBTEC.  He will now be gaining a mutagenesis platform to manipulate mosquito embryos.

Souza-Neto will use this technology to knock out genes of the Aedes aegypti related to the infection process, in an attempt to render it refractory to the dengue virus.  Scientists know that some of the natural responses of Aedes aegypti are mediated to some extent by bacteria present in the mosquito’s gut.  “The intestinal microbiota influences the development of a pathogen in the mosquito’s gut.  We want to understand the relationship between the insect’s immune system, the microbiota and the dengue virus and how this affects the development of pathogens in the mosquito,” says Souza-Neto.

In addition to laying the groundwork for new collaborative relationships, the duo will also be involved in teaching undergraduates with the goal of increasing the flow of students between the two countries.

1. Characterization of the microbiota-mediated anti-dengue mechanisms in wild Aedes aegypti populations (2013/11343-6); Grant Mechanism: Young Investigator; Principal Investigator: Jayme Augusto de Souza-Neto (Unesp); Investment: R$1,042,766.71.

2. FAPESP-Unesp-Keele University Cooperative Network: fostering Brazil and UK interactions through joint reciprocal academic activities (2014/25287-3); Grant Mechanism: Scholarship abroad; Principal Investigator: Jayme Augusto de Souza-Neto (Unesp); Investment: R$45,905.38.