Abstract: Treponema denticola is an oral spirochete associated with periodontal disease. As with other motile pathogens, chemotaxis has been implicated as a virulence factor for T. denticola. The chemotaxis signaling pathway serves as the navigation system which enables directed cell motility by regulating flagellar motor function through a series of conserved protein-protein interactions in response to environmental cues. Chemotaxis genes present in the T. denticola genome include the cheAWXY operon and the cheRB operon, in addition to a cheW homolog (cheW-2) and twenty genes for putative methyl-accepting chemotaxis proteins (MCPs). Through genetic and functional genomic studies, this dissertation investigates these proteins and their unusual features to gain a better understanding of the T. denticola chemotaxis pathway. Gene replacement mutants were constructed for two chemotaxis genes, cheW and cheR, in T. denticola. The cheW gene encodes CheW, the coupling factor of the MCP/CheW/CheA chemosensory complex, which is fused to a C-terminal CheR-like domain in T. denticola. The cheR gene encodes the CheR methyltransferase, an adaptation protein. Mutants of cheW or cheR are defective in chemotactic swarming, indicating the role of these proteins in chemotaxis and lack of complementation by their respective paralogs. Using a functional genomics approach to study the chemotaxis pathway of T. denticola, a yeast two-hybrid genomic library was constructed and tested with chemotaxis proteins as baits. CheW was found to interact with all of the putative MCPs, indicating their potential functionality. CheW also interacted specifically with the regulatory domain of CheA. CheX, a CheY-phosphatase, was shown to interact with the CheA regulatory domain, as well. Further yeast two-hybrid genomic library studies explored previously unknown protein interactions. The CheW paralog of T. denticola, CheW-2, was discovered to interact with all twenty putative T. denticola MCPs. CheW-2 was also found to interact more strongly than CheW with some MCPs. However, CheW-2 did not interact with CheA, in contrast to CheW. These results suggest that CheW-2 functions in the T. denticola chemotaxis pathway, but likely has a distinct role from CheW. Through genetic and functional genomic studies, this dissertation provides new insight into the unique features of spirochete and T. denticola chemotaxis.