Associate Professor Emeritus of Biological Sciences
PhD, 1974 University of California - Berkeley
|Office:||407 Tucker Hall|
Evolution and pathogenesis of bacteria
Research descriptionResearch description
My laboratory studies the evolution and pathogenesis of Haemophilus influenzae, a gram-negative bacterium which causes diseases ranging from otitis media to meningitis. Nonencapsulated H. influenzae (NTHI) is an important cause of many respiratory illnesses, including those which complicate cystic fibrosis and chronic obstructive pulmonary disease. In collaboration with Dr. Tom Phillips’ laboratory. I am currently investigating early events in NTHi colonization of respiratory cells, including function of the Lav protein of nonencapsulated H. influenzae, an outer membrane protein that belongs to a family of virulence-related autotransporters. A nearly identical lav gene (89% DNA identity) is found in Neisseria meningitidis, the agent of epidemic meningitis, which acquired it by lateral transfer from H. influenzae. Using tissue culture, we are looking at the role of Lav in the association of H. influenzae to cells of the human lower respiratory epithelium. The lav gene is phase-variable, mutating to the ON or OFF phase by gain or loss of tetranucleotide repeats within the 5’ end of the gene. Unlike most autotransporters, Lav is not proteolytically cleaved at the cell surface and remains full-length.
We have constructed phase-locked ON and fluorescently tagged mutants of several strains to investigate the role of Lav in cell adherence, cell invasion, autoaggregation, and biofilm formation. Other projects include genomic investigations of other horizontally transferred virulence genes, including a chromosomal NTHi gene related to a multi-drug efflux pump component that has been transferred extremely recently (>98% DNA similarity) from the animal pathogen Pasteurella multocida, and a collaborative study with Dr. Phillips’ laboratory of transcytosis of NTHI by M cells in the conjunctiva.
Smith, G.P., Golomb, M., Billstein, S.K., Smith, S.M. The Luria-Delbrück fluctuation test as a classroom investigation in Darwinian evolution. (2015) American Biology Teacher, 77 (8):614-619.
In preparation: Thomas, I., Berger, A. Casey, M., Phillips, T., Smith, A.L., and Golomb, M. (2013) The Lav autotransporter of nontypeable Haemophilus influenzae inhibits bacterial autoaggregation and mediates dispersal
Thomas, W., Golomb, M., and Smith, G.P. (submitted) Corruption of phage-display libraries with target-unrelated clones: Diagnosis and countermeasures
Honors & Awards
Selected honors and awards
Win Horner Award for Innovative Writing Intensive Teaching 2015
MU Faculty Achievement Award in Diversity 2012
MU Alumni Anniversary Award for Contribution to the Education of Women 2011
Campus Writing Program 20/20 Award 2009
Science Teachers of Missouri Distinguished Service Award 2008