Antibiotic resistance often arises not from single mutations, but from specific combinations of mutations that together change how proteins and genes function. This project will study how such mutation combinations shape the evolution of essential bacterial proteins and gene regulatory DNA. Using existing experimental data and new analyses, the student will examine how mutations interact to enable or block resistance, focusing on enzymes involved in drug response and bacterial promoter regions that control gene expression. The long-term goal is to identify rules that explain why some evolutionary paths to resistance are accessible while others are not, with direct relevance to antibiotic resistance prediction, protein engineering, and synthetic biology.