The Barber lab seeks to understand how evolutionary processes shape host immune responses and the virulence of infectious microbes. We focus primarily on molecular interactions between vertebrates and pathogenic bacteria, integrating approaches from genetics, biochemistry, microbiology, and cell biology. Below are some examples of current project areas in our lab.
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.
Recently we have been studying 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. We are now expanding our investigation of evolutionary conflicts between bacteria and primate hosts in relation to other antibacterial immune defenses.
IMMUNE PROTEIN EVOLUTION
Long-term co-evolution 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? We are exploring the origins of immune protein functions as well as how these activities diversify in response to selection by pathogens. We are also interested in applying these insights to engineer to activities of existing immunity proteins.
MECHANISMS OF BACTERIAL ADAPTATION
Many bacteria are restricted to life in a single host species, but the mechanisms underlying this specificity are often unclear. In addition, bacteria capable of causing disease in humans often colonize a large proportion of the populations asymptomatically. These two observations can be explained in part by genetic variation in bacterial and host populations. One of our emerging goals is to determine how bacteria adapt to the host environment and identify new genetic factors that impact 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.