This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Project #1 - The protozoan parasite Toxoplasma gondii is a serious global pathogen that infects nearly one third of the adult human population. Despite its importance, very little is known about how this parasite initially engages a host cell in order to establish infection.
The aim of this proposal is to characterize the molecular interactions that enable T. gondii to attach to, and ultimately invade virtually every nucleated cell. More specifically, we will characterize the structural basis of how key members of a superfamily of developmentally expressed surface proteins on T. gondii (known as the SRS adhesins/antigens) mediate parasite attachment to host cells. Based on this work, we will be strategically poised to develop therapeutic interventions, either prophylactic or vaccine-based, to limit infectivity of this widespread zoonotic pathogen. Project #2 - Xenobiotic aromatic compounds represent one of the most significant classes of environmental pollutants. There is an ever growing need for inexpensive, biologically based solutions to deal with these types of aromatic molecules such as those found in crude oil, PCBs or industrial effluents. Remediation of these contaminated sites is both technically challenging and expensive. A promising strategy to stimulate the removal of these contaminants from the environment is to manipulate the metabolic pathways of bacteria. As a prerequisite step to the rational engineering of these biological systems, detailed descriptions of the enzymes involved are essential. Towards this end, my research program is focused on characterizing the structural properties of novel aromatic catabolic enzymes from a potent PCB-degrading bacterium. The long-term objectives of this research program are to design more efficient strategies for the bioremediation of environmental pollutants.
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