One large group of soil bacteria known as 'rhizobia' have the ability to engage with plants in a permissive bacterial infection process on compatible host plants, leading to specialized plant root organs known as root nodules. In these root nodules, the bacteria multiple, actively invade plants cells, and differentiate into nitrogen fixing cells called bacteroids. This arrangement between the plant and bacteria will supply the plant with enough fixed nitrogen to maintain plant health in environments where nitrogen supplies are limited in the soil. In exchange for fixed nitrogen, the plant supplies rhizobia with carbon resources derived from photosynthesis. This cooperative interaction occurs in biomes worldwide and is a major driving force in terrestrial nitrogen cycling. This process is also central to the concept of crop rotation in many agriculture settings. In addition to its economic and ecological implications, this symbiotic interaction provides a wonderful mechanism to study the complex interactions that are essential in inter-kingdom signaling and communication, which have been evolving for millions of years. Our goals as a laboratory are to discover and closely examine which genes allow the bacteria to communicate with its plant host and which genes that plant uses to respond to the bacteria, creating a permission infection of its roots. We primarily focus on the bacterium Sinorhizobium meliloti and its nodulating plant hosts of the genus Medicago including alfalfa. We use many molecular approaches, including transposon mutagenesis, bacterial conjugation, molecular cloning, protein biochemistry, and protein expression technology to help us better understand the pathways that drive this host-microbe interaction.