About This Project

The recent zika outbreak highlights the importance of personal mosquito protection. The chemical DEET has been the gold standard in mosquito repellency since its civilian use began in 1957. DEET has important drawbacks and little is actually known about how it works. We wish to study how DEET manipulates the mosquito's senses to provide information that can lead to the development of more effective repellents to combat mosquito transmitted diseases.

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What is the context of this research?

DEET manipulates olfactory receptors to repel mosquitoes but how that occurs is controversial. The primary targets of DEET are the odorant receptors (ORs), but another family of olfactory receptors, the ionotropic receptors (IRs) may also be involved. DEET may work by scrambling the perception of human odor or directly activating the ORs. Recently, Ir40a has been identified as a DEET receptor in the vinegar fly, Drosophila melanogaster, opening the possibility that the gene plays a similar role in mosquitoes. Using genome editing techniques we can study the two Ir40a genes in Aedes aegypti to determine if they play a role in mosquitoes aversion to DEET. This research could provide a new molecular targets for mosquito repellent design.

What is the significance of this project?

Mosquitoes serve as carriers (vectors) for diseases such as malaria, dengue, chikungunya , and zika. Currently, Central and South America as well as the Caribbean are experiencing an outbreak of zika. Infection is spreading, with pockets popping up in other areas of the world as well. Recent evidence suggests the zika virus may cause microcephaly, a devastating birth defect. As governments continue their global efforts to combat this mosquito borne disease, the most effective strategy an individual can take is the use of mosquito repellents, preferably DEET. DEET although highly effective and safe , it is by no means foolproof and how it works is poorly understood. Determining how DEET manipulates olfactory receptors will inform the development of more effective repellents.

What are the goals of the project?

Understanding the mechanism of DEET repellency is crucial for the development of better mosquito repellents to keep mosquitoes from biting people and transmitting disease. This project will distinguish between competing theories on how DEET disrupts mosquito attraction to human hosts. We will determine whether DEET works as a repellent on its own or in combination with host odors using our custom designed mosquito traps. In addition, we will determine the role that Ir40a and Ir40b play in mosquito aversion to DEET by generating a mosquito that lacks these genes. It is possible the Ir40a and Ir40b mutant mosquitoes will not be repelled by DEET. If this is case, we will have found a new way that DEET can repel mosquitoes.

Budget

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We are asking for your support to purchase critical items to get this project started:

1. To make mutant mosquitoes, we use the CRISPR-Cas9 genome editing technique. This requires the generation of an RNA that guides a nuclease to specific site in the mosquitoes genome and causes a break in the DNA.

2. Genotyping allows for the identification and subsequent tracking of the mutations we will generate. This requires the purchase of costly molecular biology reagents.

3. Mosquito rearing involves the maintenance of a rearing room and the tools needed to raise a mosquito from egg to adulthood in an controlled environment. You will be helping the lab expand its mosquito rearing capacity to accommodate the care and feeding of the new mutant strains.

4. Custom made mosquito traps will be used to collect valuable data about how DEET works. These traps are designed by us and fabricated locally in Miami.

Previously I was covering the microinjection. With the stretch funds you can lend a hand.

Endorsed by

I am very excited about this project. It will fill an important gap of knowledge in the field. The team of investigator are highly qualified to succeed. I endorse the project without any doubts.

Fernando Gabriel Noriega

Professor

Florida International University

Dr. DeGennaro is an excellent scientist working on this problem. This is important work and should be supported

Anthony James

Distinguished Professor

Universty of California

Dr. DeGennaro's proposed research is absolutely critical in the fight against zika. With your support his team will gain crucial knowledge required to design a new and improved wave of mosquito repellents..even more effective than DEET!

Conor McMeniman

Assistant Professor

Dr. Degennaro's project is hugely important for stopping the spread of Zika and other mosquito-borne diseases. His unique expertise makes him THE man for understanding how mosquito repellants work, and how they can be made more effective.

Philip K. Stoddard

Professor (& Mayor of South Miami)

FIU

Mosquitoes transmit many diseases. Understanding the mechanism of DEET repellency will inform new chemicals or new approaches for better protection. This exciting project is trying to address this important question, and Dr. Degennaro is an excellent PI to conduct this research. I am happy to endorse this project.

Jun Li

Assistant Professor

University of Oklahoma

Meet the Team

Matthew DeGennaro

Assistant Professor

Affiliates

Florida International University

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Paola Martinez

Researcher

Affiliates

Florida International University

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Freddy Mappin

Researcher

Affiliates

Florida International University

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Team Bio

Understanding how mosquitoes sense their human and plant hosts is required for the development of new tools to control harmful mosquito behaviors. Using a molecular genetic approach, the DeGennaro lab seeks to identify the odors and olfactory receptors that are necessary for mosquito host detection. Understanding how DEET repels mosquitoes is a key question for the lab. Our DEET team is focused on determining how DEET manipulates olfactory receptors to drive repellency.

Matthew DeGennaro

I am a neurogeneticist with over 20 years of experience in biomedical research. My research program at Florida International University seeks to understand the molecular mechanism of mosquito attraction and repellency. During my post-doc at Rockefeller University, I created the first mosquito mutant using zinc-finger nucleases to initiate the molecular genetic analysis of olfactory receptor function in Aedes aegypti. This mosquito is responsible for the transmission of dengue, zika, chikungunya, and yellow fever. My work revealed new knowledge about the integration of host cues, mosquito host-preference, mosquito nectar-seeking, and the mechanism of DEET repellency. My current goal is to identify olfactory receptors that mosquitoes use to sense their human and plant hosts. Genetic analysis and expression pattern mapping of these receptors are crucial first steps to understand how the mosquito codes host odor information. My research program will provide molecular targets that can be used to screen for new chemicals to modify mosquito behavior.

A review on DEET repellency I recently published.

My lab's website.

My CV.

Paola Martinez

I am a third year Biology major, as a QBIC Scholar and an NIGMS-RISE Fellow. My research interests lie within neuroscience and neurogenetics. My focus is understanding how the compound DEET alters olfactory receptors to disrupt the mosquito's interaction with human hosts.

Freddy Mappin

I am currently a biology researcher in Dr. DeGennaro's lab at Florida International University. My graduate work will focus primarily on understanding the mechanisms of repellency in Aedes aegypti. Our research program is focused on the olfactory receptors that mediate the mosquito’s human and plant host-seeking behavior and the genes that regulate their appetitive drives. My project focuses on understanding the mechanisms of DEET repellency in the hopes of developing more efficient mosquito behavioral control chemistries.