The laboratory is focused on genetic determinants of bacterial pathogenesis in Neisseria meningitidis and Streptococcus pneumoniae (important causes of meningitis and bacteremia) and other bacterial pathogens, on the discovery and development of bacterial vaccines and on the activation of the human innate immune system by bacterial ligands. These studies include the molecular mechanisms of attachment, colonization and invasion of human mucosal surfaces by pathogenic bacteria, conjugative transposons and role of transposons in bacterial virulence and antibiotic resistance, capsule structure and immunogenicity, and endotoxin structure and the interactions with MD-2 and TLR4. We are examining the genetic, structural and pathogenic basis of meningococcal lipopoly(oligo)saccharide, and meningococcal capsule and the role these ligands play in innate immune recognition. A better understanding of how pathogenic bacteria cause disease and engage the immune system is needed for new strategies for the design of vaccines and vaccine adjuvants that will protect against serious bacterial infections. To this end work of our group is involved in the evaluation of human responses to saccharide and conjugate vaccines, population effectiveness of these vaccines in particular transmission and herd immunity effects and vaccine introduction strategies.