Dr. Luiz Bermudez has been awarded an NIH RO1 funded grant for his proposal “Genes associated with M. avium pathogenesis.”
This award is for $2,100,000 over five years, March 2010-February 2015.
- The grant is to study the mechanisms used by Mycobacterium avium to survive and replicate within host macrophages. Mycobacterium avium is a human and animal pathogen, that causes lung and disseminated disease. Mycobacteria live within cytoplasm vacuoles in macrophages, blocking vacuole maturation, by inhibiting acidification and fusion with lysosomes. The group is working in the understanding of mechanisms such as the bacterial-driven modification of the mycobacterial vacuole inside macrophages, making it a suitable environment for replication. The group has found genes/proteins which modify the vacuole membrane content upon cell uptake, as well as suppress the host innate immune response triggered by macrophage’s surveillance sensors. They are also working with a M. avium protein that selectively inhibits endosomic proteins involved in the maturation of the phagosome. They have also discovered bacterial genes associated with the M. avium’s ability to resist the killing mechanism in macrophages. For instance, genes/proteins linked with the bacterial resistance to nitric oxide, antimicrobial peptides and even unknown macrophage killing mechanisms. They are also working in the understanding of how bacteria escapes macrophages once they undergo apoptosis, as a strategy to kill the intracellular aggressor. A combination of cell and molecular biology, biochemistry and genomics to understand pathogenesis.
Dr. Dan Rockey has been awarded an NIH R21 funded grant for his proposal “Analysis of chlamydial recombination in vivo.”
The award is for $402,050 over two years, April 2010-March 2012.
- Although chlamydiae are challenging to work with in the laboratory, one thing they do very well is recombine their chromosomes. What this means is that two strains of chlamydiae can be mixed together in the laboratory, and they will basically mix and match their genomes. We have identified clinical strains that appear to have recombined in patients, and we are exploring whether or not we can model this “in vivo recombination” in an animal system. These studies will help us to evaluate the role of individual chlamydial genes in disease, and provide important information about possible vaccine or therapeutic drug targets.