Animals often live in close association with bacteria and other microbes. The most intimate form occurs with endosymbiotic bacteria which reside inside the cells of its host. The widely accepted bacterial origin of mitochondria illustrates the key role endosymbionts have played in animal evolution. Among bacterial endosymbionts, the interaction between Wolbachia and their hosts is one of the most successful. Wolbachia are gram-negative bacteria present worldwide in over 70% of all insect species as well as numerous nematodes. Because Wolbachia replicate and concentrate in the female reproductive organs and are efficiently passed to the eggs, they have an amazing ability to rapidly spread through uninfected insect populations. Currently little is known about how Wolbachia replicate and concentrate in the female germline. Therefore the research in this project is aimed to precisely define the molecular components in the insect reproductive cells that interact with Wolbachia to facilitate their transmission. An exciting aspect of these studies is that they provide a molecular understanding of the global spread of Wolbachia throughout insect communities.

Broader Impacts

This project is built on material and concepts that are taught in genetics and cell biology classes and is therefore well suited for undergraduates and graduate students. The research relies on the Drosophila model system, which has abundant publicly available genetic tools, thus providing opportunities for relatively quick success in generating results, which is so important for those just beginning their research career. While pursuing these projects, the students will also become proficient at using many of the extensive Drosophila molecular and genetic databases available. In addition, large-scale genomic functional screens are a key part of this project and involve the use of newly developed technology, including robotics and automated microscopy. This provides excellent training for those pursuing careers in the biotech industry as well as academics. While technically demanding, a dedicated student can become very adept and able to generate publishing-quality data within a couple of months. In the laboratory, each undergraduate is paired with a senior graduate student or post-doctoral fellow. This is ideal to produce rewarding undergraduate projects with skilled daily supervision while giving the graduate students and postdoctoral fellows the chance to supervise students as a part of their training within the larger scope of their research. Wolbachia is also of tremendous interest to the agricultural community as an alternative to pesticide-based insect eradication programs. For this reason, rare virulent Wolbachia strains have generated considerable excitement. To identify additional virulent strains, we rely on undergraduates to collect and analyze Wolbachia-infected Drosophila from wild populations. These studies provide opportunities for students to understand the connection between the cell biology of Wolbachia-host interactions and their effect on insect populations. In addition to ongoing regular classes, an intensive one-week course for minority undergraduate students is taught in the summer that includes molecular biology as well as camping and insect collections at the Big Creek field research station in order to identify new Wolbachia strains.

Project Report

Wolbachia is a species of bacteria that resides in the germline of majority of insect species making it one of the most widespread bacteria on the planet. It is passed on from one generation to the next strictly through the germline of its female host. Consequently Wolbachia manipulates its host in variety of fascinating ways to favor infected female insects. This includes converting males into reproductive females, killing the males in an infected population, and inducing parthenogenesis (virgin birth). It should be noted that Wolbachia resides in filarial nematodes and is the causative agent of River-blindness and Elephantiasis diseases afflicted 160 million globally. In spite of Wolbachia’s biological importance, little is known concerning how it interacts with its host at the molecular and cellular level. In this project by taking advantage of automated microscopes, robotics and powerful image recognition software, we were able to survey the entire genome of Drosophila melanogaster for host genes that influence Wolbachia abundance in insect cells. This study reveals a number of host factors required for Wolbachia replication including factors involved in protein degradation. These studies also revealed that Wolbachia abundance depends on the host diet. A high yeast diet result in decreased titer while an high sucrose diet results in increased Wolbachia titer. Genetic analysis reveals that the influence of Wolbachia abundance on host diet relies on the conserved insulin signaling pathway. We took advantage of our high throughput cell-based screen to identify compound that kill Wolbachia. These compounds are useful for basic research into Wolbachia biology. In addition, they may also be useful in combating the devastating neglected diseases of Riverblindness and Elephantiasis. In a related set of studies, we examined the host mechanisms required for Wolbachia to migrate to the posterior pole of the mature oocyte. Our studies demonstrated that Wolbachia relies on intracellular fibers known as a microtubules. Specialized proteins called motor proteins normally move specific cellular cargos along these microtubule highways. We discovered that Wolbachia has evolved to engage these motor proteins in order to efficiently concentrate in the mature oocyte. Our studies also identified specific host protein that links Wolbachia to these molecular motors. Finally we examined whether Wolbachia relies on microtubules and motor protein for transport to the posterior pole of filarial nematode embryos. It turns out that engaging microtubules and motor proteins appears to be a conserved feature of Wolbachia host interactions. In addition, we discovered that Wolbachia is unique among symbionts in that it is required for proper establishment of the anterior-posterior embryonic axis of the developing filarial nematodes.

National Science Foundation (NSF)
Division of Molecular and Cellular Biosciences (MCB)
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Gregory W. Warr
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University of California Santa Cruz
Santa Cruz
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