Our central goal is to determine how evolutionary processes shape host immunity as well as microbial pathogen virulence. Below are some 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 protein 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 such 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 a potent 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 that contributing to nutritional immunity. We are currently expanding our investigation of evolutionary conflicts between bacteria and primate hosts in relation to additional 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 processes by which immune protein functions emerge as a consequence of host-microbe associations as well as strategies to engineer the activity of animal immunity factors.
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, numerous bacteria capable of causing disease in humans colonize a large proportion of the populations asymptomatically. One of our emerging goals is to determine the genetic and molecular basis by which bacteria adapt to the host environment and identify factors that impact host-associated bacterial behavior. In addition to advancing our understanding of the fundamental process of adaptation, pinpointing the determinants of host specificity in human pathogens could reveal new avenues for infectious disease treatment and prevention.
Current research sponsors:
Past research sponsors: