Kim Orth wants to understand how pathogenic bacteria invade and manipulate host cells. Orth and her team use a multifaceted approach including biochemistry, biophysics, cell biology, genetics, and cellular microbiology. The team has uncovered virulence strategies that pathogens – such as Yersinia, which causes plague, and Vibrio parahaemolyticus, a cause of food poisoning – use to manipulate host cells. From these pathogenic strategies, they have gained insight into new chemistry used by molecular signaling systems in cells; for example, the evolutionarily conserved Fic protein that uses AMPylation to critically assess proteostasis within the endoplasmic reticulum, preventing the system from overloading and cells dying. Such chemical mechanisms can be exploited to treat disease.