Bacterial pathogenesis is a multi-factorial process and bacterial infection can be considered as a battle between the host's immune system and the invading microbe. Both the microbe and the host invoke a myriad of faculties in this process as the battle between the microbes and the host's immune system begins to unfold. The primary resources that are invoked by the microbes are perhaps crucial for its survival. It is here that the adhesive and the secreted proteins appear to form the first line of scrimmage for the microbe. The interactions (adhesion) that occur between the microbes and the extracellular matrix components appear to play an important role. The goal of studies in my lab is to elucidate crystal structures of these adhesive molecules and identify their respective binding-motifs. This would first satisfy the academic quest towards understanding the fundamentals of bacterial adherence, and secondly extend into the applicative realm wherein, the design of inhibitors or passive immunization directed at the binding-site could provide a viable avenue toward development of therapeutics.
We are now funded by NIH to structurally elucidate the interactions that occur between the surface protein Antigen I/II of Streptococcus mutans, a dental pathogen and a known etiological agent in dental caries.
We are also interested in studying, the fimbriael proteins of Porphyromonas gingivalis, another dental pathogen. Towards this we have now cloned and expressed two fimbriael proteins fimA and Mfa1.
In addition to these projects, we have embarked upon utilizing the Streptococcus agalactiae bacteriophage's hyaluronan lyase, HylP in cancer cells, which has now been shown to inhibit both breast cancer cell proliferation and invasion. Structural studies are being carried out in a effort to identify its active site.
My mission as a structural biologist is to elucidate structures of important biological molecules and to decipher their mechanisms in protein-protein interactions. Particularly, I am interested in two areas, 1. Hyaluronan (HA) biology as related to cancerous tumors and identification of enzymes that would reduce the levels of HA, which could result in reduction of cancer cell growth, migration and invasion, and 2. Surface microbial components that play a crucial role in the etiology of disease progression. As the Co-director of the Comprehensive Cancer Center’s X-ray Core facility, I am well positioned to execute the requirement of fair allotment of time between the users of the facility, particularly to exercise discretion in allocating priority to projects that are currently funded by NIH. In addition to maintaining the facility, I also play an active role in strategic planning initiatives that would result in improved user access, acquisition of state-of-the-art instrumentation, as well as serve on the SER-CAT board. In this proposal we seek NIH funds towards upkeep and maintenance of the X-ray core facility, which has been a part of UAB’s Comprehensive Cancer Center since 1987.