Viruses are ubiquitous throughout nature, are incredibly diverse and are major players in the global ecosystem. Understanding host-pathogen interactions is critical for treating infectious disease and developing new tactics to combat emerging threats. This PhD work has sought to dissect the molecular mechanisms governing 1) the assembly, acquisition, and transmission of plant viruses by insect vectors and 2) the bi-stable switch and exclusion activity of bacteriophage lambda. Toward those ends, my work in this lab first addresses luteovirids which are icosahedral, positive sense RNA viruses that cause economically important diseases in staple food crops. Viruses in these genera are transmitted between plants by phloem-feeding aphids in a circulative manner that involves the movement of viruses across and within insect tissues. I have determined the crystal structure of a truncated version of the potato leafroll virus coat protein to 1.8 Å, providing new insights into polerovirus assembly and maturation. I also helped solve the 1.53 Å crystal structure of the N-terminal readthrough domain from turnip yellow virus, which we found to be a potent inhibitor of viral transmission and from which we could rationalize the sub-stoichiometric incorporation of the readthrough protein into the infectious viral particle.The second avenue of my research has focused on characterizing the RexA protein from lambda phage, which binds DNA non-specifically and functions in both anti-phage defense and modulation of the lysogenic to lytic transition. Through X-ray crystallography, mutagenesis, and a battery of biochemical assays, I uncovered a conformational change is required for RexA DNA binding. I have further demonstrated that RexA homologs from temperate phages Sbash, CarolAnn, and Toast share similar DNA binding properties in vitro, which has important evolutionary implications for how the life cycles of these viruses may be regulated. Taken together, these studies advance our fundamental understanding of prokaryotic biology and plant pathology, respectively, and have important translational impacts for treating antibiotic-resistant bacterial infections and mitigating crop loss in agricultural settings.