Our lab seeks to understand how evolutionary processes shape host-pathogen interactions and resistance to infectious diseases. We focus primarily on molecular interfaces between vertebrates and pathogenic bacteria, integrating approaches from genetics, biochemistry, microbiology, and cell biology. Below are a few examples of current project areas.
HOST-MICROBE EVOLUTIONARY CONFLICTS
Infectious diseases are a potent force of natural selection. Repeated episodes of adaptation at host-microbe interfaces can lead to molecular ‘arms races,’ providing some of the most dramatic examples of rapid evolution observed in nature. Our group is working to identify biological pathways subject to host-pathogen conflicts and the factors that govern their outcomes.
Previously we have explored evolutionary conflicts between bacteria and primates relating to the essential micronutrient iron. In addition to dedicated immune defenses, the sequestration of iron by host proteins provides an important barrier to infection termed nutritional immunity. Microbes in turn deploy dedicated iron acquisition factors, including secreted siderophores and cell surface receptors, in order to scavenge this nutrient from the host. Our research indicates that this ‘battle for iron’ has been a hotspot of evolutionary conflict during millions of years of primate divergence, driving rapid diversification of proteins contributing to nutritional immunity (Barber et al., 2014, Barber et al., 2015, Choby et al. 2018). Our ongoing work indicates that evolutionary conflicts with bacteria have been pervasive during animal evolution, involving host factors involved in microbial colonization, barrier defense, and pattern recognition receptors. We are currently applying a combination of computational and empirical approaches to determine the consequences of these conflicts for defense against human bacterial pathogens.
EVOLUTION OF IMMUNE DEFENSE
Long-term coevolution of microbes and hosts has produced an array of remarkable biological innovations including adaptive immunity in vertebrates as well as CRISPR-Cas defense systems in bacteria and archaea. How has the amazing complexity of the immune system evolved, and what unique activities remain to be discovered? Work by our group and others recently demonstrated how rapid diversification of immune defense proteins in primates has enhanced recognition of intracellular bacterial pathogens (Kohler et al., 2020). These findings illustrate how exploring diversity in immunity genes can reveal functions that are hidden through studies of humans alone. We are continuing to investigate how host immune protein evolution shapes microbial recognition to identify new pathways to target human pathogens.
Many microbes are restricted to life in a single host species, but the mechanisms underlying this specificity are often unclear. In addition, pathogens capable of causing disease in humans often colonize a large proportion of the population asymptomatically as harmless commensals. These observations can be explained in part by genetic variation within microbial and host populations which underlies disease progression and species tropism. One of our emerging goals is to determine how bacteria adapt to the host environment and identify new factors that impact bacterial pathogenicity. In addition to advancing our fundamental understanding of the evolutionary process, identifying determinants of host specificity in human pathogens could reveal new avenues for infectious disease treatment and prevention.