Research in the Lazzaro Lab is focused on the evolutionary genetics of insect-pathogen interactions. We use population genetic, quantitative genetic, and genomic approaches to study how insects defend themselves against infection. We are particularly interested in understanding the genetic and environmental reasons why individuals vary in their susceptibility to infection, how interactions with pathogens shape the evolution of host immunity, and how immune defense is intertwined with other components of host physiology. We do most of our experimental research on the genetic model insect, Drosophila melanogaster, which allows us to combine functional genetic manipulation with studies of natural genetic variation. We also do population genetic and genomic work in Anopheles mosquitoes that vector malaria in sub-Saharan Africa.

Individual Variation in Defense

Experimental infection of a D. melanogaster with bacteria.

Effects of nutrition on immunity

Comparison of systemic bacterial load after infection of 170 D. melanogaster genotypes provided with either high-sugar or low-sugar diets reveals GxE for resistance to infection.

Effects of reproduction on defense
We have found that female D. melanogaster become significantly less able to resist infection upon mating, suffering higher mortality and reduced ability to regulate pathogen growth. This effect is not due simply to the act of copulation, but seems to result from a physiological change in the female that presumably reflects a shift from virgin homeostasis to active production of mature eggs. Thus, reproduction and defense against infection are antagonistically linked in a physiological tradeoff. Notably, female D. melanogsater vary genetically in the degree to which they become immunocompromised after mating (although males show no variation in their ability to immunosuppress their mates). Working in collaboration with Mariana Wolfner, we are currently working to identify the molecular mechanisms for post-mating immunosuppression in D. melanogaster females and the evolutionary consequences of this life history tradeoff.

Key papers from the lab in this area

Molecular evolution of insect immune genes

We use molecular population genetic and comparative genomic analyses establish how natural selection operates on the immune systems of Drosophila melanogaster, Anopheles mosquitoes that vector human malaria, and other insect species. We ask what are the natural selective, demographic and epidemiological pressures that drive evolution of insect immune systems, and how population-level phenomena such as population subdivision, migration, local adaptation, and changes in population size may affect the evolution of defense.

Rapid duplicaiton and deletion in the Cecropin antimicrobial peptide gene family across the genus Drosophila.

Molecular population genetics of Anopheles mosquitoes
Malaria is a devastating disease, particularly in Africa, with hundreds of millions of clinical cases and nearly a million deaths reported each year. Even within single populations, however, mosquitoes are highly genetic polymorphic for the ability to transmit disease. Together with Ken Vernick's group at Institut Pasteur, we have been studying the evolutionary genetics of A. gambiae, the epidemiologically most important vector of human malaria. A. gambiae subpopulations are extremely fragmented, with restricted interbreeding and genetic exchange among them. We have fitted models to population diversity data to determine the demographic history of two major subgroups of A. gambiae, known as the "M" and "S" molecular forms. We find these potential incipient species to be have distinct evolutionary trajectories, possibly including differential selection on the hyperpolymorphic APL1 family of anti-malaria genes. We are currently engaged in multi-locus analyses of evolutoin and diversity of the A. gambiae immune system. We hope that better understanding of the evolution of anti-malaria defense genes in Anopheles will suggest potential targets for intervention, and that appreciating demographic structure in mosquito populations will lead to more effective control, ultimately reducing malaria transmission and the human disease burden.

Key papers from the lab in this area

Infection genomics in bacteria

Comparative genomics and pathology of bacteria recovered as natural infections of D. melanogaster.

Key papers from the lab in this area