The Genetic Architecture of Maternal Supression of Symbionts

At the turn of the 20th century, biologists asserted that babies develop within a sterile womb and acquire their initial bacteria from the environment. While this paradigm is under preliminary reconsideration today in light of new technologies and analyses, comparative studies of animals have long held that maternal provisioning of bacteria to offspring is widespread, spanning the base of the animal kingdom to vertebrates. Moreover, such bacteria are not simply innocuous passengers. They impart vital consequences to animal health and disease, and they have their own microbial interests, namely their propagation from mother to the next generation. In this context, there is a biological conundrum between host and maternally transmitted bacteria. High loads of bacteria can lead to pathogenesis in the animal offspring while low concentrations can lead to loss of the bacteria. Balancing these opposing outcomes in the middle is one possible way to reconcile the extremes. Thus, the critical biological question is how are the concentrations of maternally transmitted bacteria regulated? Using a preeminent animal-microbe model, the investigators will genetically test the hypotheses that (i) animal hosts express multiple (rather than single) genes to control the concentrations of maternally transmitted bacteria (ii) when these genes are disrupted from their normal functions, the bacterial densities transmitted to the offspring will increase and (iii) these genes control the bacteria by preventing them from entering the developing offspring and repressing their replication. This project will be the first study to deploy a unique genetic analysis that characterizes the animal genes that keep bacterial densities in check. The Principal Investigator will direct a one-week workshop for pre-service teachers (college students working towards a degree in education) based on the premise that the earlier that teachers participate in 'discovery science', the more likely they will feel comfortable using it in the classrooms. The researchers will also partner with the School for Science and Math at Vanderbilt to develop a Community Engaged Research Project in which Nashville high school students transfer experiential learning from the research lab back to their classrooms to engage in the process of cooperative and peer-to-peer learning for science- and technology-related investigations.

The majority of animal species harbor maternally-transmitted bacteria, yet little is known about the genetic and molecular mechanisms that the animal and bacteria use to achieve maternal transmission. For symbionts transmitted via the germ-line, bacterial density can critically influence transmission efficiency and penetrance of symbiotic traits induced by the symbiont. This research begins the first forward-genetic investigation of host genes that regulate densities of Wolbachia pipientis. The genus Wolbachia is a model endosymbiont because it occurs in more animal species than any other bacterium on the planet, and it can range from a beneficial symbiont in filarial nematodes, a parasitic manipulator of arthropod reproduction, to the main inflammatory agent of human filarial diseases. However, despite infection's prevalence, few host-Wolbachia interactions have been identified that control their densities. As a model host with genetic tools, the Nasonia parasitoid wasp genus is comprised of several closely related species that harbor unique strains of maternally-transmitted Wolbachia in their reproductive tissues. Transfer of these Wolbachia strains between the interfertile Nasonia species can result in dramatic changes in infection titers and tissue tropism. Specifically, the wVitA strain maintains a low infection density in its natural host, Nasonia vitripennis, but has a wider tissue tropism and stable infection density 100-fold higher in the naive host, Nasonia giraulti. Quantitative trait loci analyses specify that the regulation of the low wVitA density maps to three N. vitripennis chromosomal regions. This host regulation acts dominantly through a maternal effect - the mother determines the densities of her offspring. Thus, the central hypothesis of this research project is that multiple genes involved in host innate immunity and/or oogenesis act maternally to regulate Wolbachia densities in offspring. The goal of this project is to utilize an unprecedented interspecific difference in Wolbachia titers to identify the numbers and types of host genes that regulate Wolbachia densities, their additive and epistatic interactions, and their effects on Wolbachia localization and proliferation during oogenesis.