Forest Laboratory Research Focus
With the advent of antibiotics in the 1940's, society assumed the threats and fears of bacterial disease were overcome. In the current decade, the explosion of our knowledge about microbes not only as disease causing organisms but also as beneficial, desirable symbionts present in staggering diversity within us and in our environment has completely changed how we think of these tiny organisms. While on one hand antibiotic resistance and newly emerging microbial diseases are among the greatest threats to human health, on the other hand we are beginning to understand some of the broad unexpected implications of our increasingly sterile lifestyle.
The Forest lab studies the structural aspects of microbial interactions with humans, using x-ray crystallography and complementary techniques. Our focus is the structure and assembly of Type IV pili, surface organelles that mediate attachment of bacteria to eukaryotic cells, to each other, and to non-living surfaces. Pili are also required for twitching motility, which allows bacteria to slither over and colonize eukaryotic host cells. Our crystal structures of the pilus retraction protein PilT, a conserved nucleotide-binding protein essential for twitching motility, suggests that domain motions in an asymmetric motor drive pilus retraction. Eventually, our understanding of the structure, assembly and antigenicity of pili and the mechanism of their assembly and retraction may lead to vaccines against pathogenic bacteria with Type IV pili.