Harnessing Wolbachia-induced conditional infertility for control of the malaria mosquito

Wolbachia endosymbionts hold strong potential for the control of vector-borne infections. Indeed, these bacteria are currently used to control dengue virus transmission by Aedes aegypti, where they combine the ability to spread through populations via Cytoplasmic Incompatibility (CI) with efficient blocking of arboviral infections. For decades, however, scientists have been puzzled by the apparent lack of both natural and artificial Wolbachia infections in Anopheles, the vectors of human malaria, with only a handful of examples reported. Wolbachia are genetically intractable, making functional study of both their reproductive manipulations and this host tropism difficult. However, previous work suggests that a Wolbachia-derived CI-inducing factor, CifB, causes severe abnormalities in females (rescued by a different gene, cifA), that may in part prevent Wolbachia from establishing natural infections in Anopheles mosquitoes. Using a combination of genetics, cell biology, molecular, genomic and bioinformatics approaches to address key questions related to Wolbachia toxicity and rescue across different insects, these studies will push the field of insect-endosymbiont interactions into new areas of inquiry and will also generate tools for the generation of Wolbachia-based strategies for the control of malaria-transmitting Anopheles populations. Kelsey Leanne Adams will conduct the K99 phase of this award as a post-doctoral researcher in Dr. Flaminia Catteruccia’s group at the Harvard T.H. Chan School of Public Health. The laboratory is exceptionally well-equipped to establish transgenic insects and is one of the only vector biology labs with a robotic micro-injector and a COPAS Biosorter in addition to a world-class Plasmodium infection facility. Dr. Catteruccia is supported by the Howard Hughes Medical Institute, which allows flexibility of research funds which can be drawn upon for this project, and facilitates access to state-of-the-art equipment, facilitating expansive research in vector biology. In addition to Dr. Catteruccia’s expertise in mosquito reproduction, mosquito transgenesis, and host-parasite interactions, Adams will be supported by Dr. Zhiyong Xi, an expert at the forefront of Wolbachia-based vector control implementation in Aedes mosquitoes, and in establishing Wolbachia infections in Anopheles. Further, Adams will collaborate with Dr. John Beckmann, a molecular biologist and biochemist with expertise working with Wolbachia’s CI-inducing factors, and Dr. Lauren Childs, a mathematical modeling specialist. Additional mentors will include local researchers Dr. Daniel Neafsey, who has vast experience with functional genomics in Wolbachia, Anopheles, and Plasmodium, and Dr. Paul Garrity whose group excels at genetic engineering of various Dipterans.

NIH Project details

Vector Control

Jun 2024 — May 2026

$125,250

United States