We study how animals have evolved to defend against pathogenic microbes, and how microbes evolve to survive within animal hosts.
EVOLUTION OF HOST IMMUNE DEFENSES
Infectious diseases are a potent force of natural selection. Repeated 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 lab investigates how humans and other animals have evolved to recognize and respond to pathogenic bacteria. We apply genetic and genomic approaches to identify patterns of rapid evolution in immune defense genes combined with laboratory experiments to test the functional consequences of host genetic variation.
Through our research we have identified evidence of repeated adaptation among primate immune receptors which can enhance the ability of these proteins to detect bacterial pathogens (Kohler et al., 2020; Paterson et al., 2021). We have also discovered that rapid divergence of host factors required for bacterial colonization and growth can lead to changes in host specificity (Barber et al., 2014; Baker et al., 2022). These studies have collectively revealed key barriers to cross-species pathogen transmission, and how these barriers are overcome during zoonotic disease outbreaks.
Bacteria and fungi are faced with a variety of challenges when colonizing the host environment including predatory viruses, competing resident microbes, nutrient limitation, and the host immune system. One of our major goals is to determine how microbes adapt to overcome these obstacles. We perform experimental evolution to track the process of microbial adaptation in real time, as well as develop molecular and genetic tools to assess the impact bacterial diversity on disease-associated functions. In addition to advancing our fundamental understanding of the evolutionary process, identifying determinants of adaptation in human pathogens could also reveal avenues for infectious disease treatment and prevention.
A growing area of interest in our lab are the microbes that inhabit our skin, including the pathogen Staphylococcus aureus. This bacterium colonizes a large proportion of the human population without harm, but is also a leading cause of skin infections, pneumonia, sepsis, and other deadly conditions. S. aureus is notorious for its resistance to antibiotics, particularly methicillin resistant S. aureus (MRSA) isolates. We are currently applying a range of approaches to understand how S. aureus and other bacteria evolve to colonize the skin, as well as how these microbes adapt in response to one another. Through this work we aim to leverage the skin as a tractable system to study microbial evolution and ecology as well as discover new avenues to combat deadly bacterial infections.