Grant: Discovery Grants Program - Individual

My research is trying to discover how acyl carrier protein (ACP), a key central protein in bacterial fatty acid synthesis, can recognize and discriminate among its multiple protein partners. These partners include over three dozen enzymes involved in synthesis of membrane lipids, toxins (eg. endotoxin), and other essential components of bacterial growth and pathogenesis. ACP must fold to enclose attached fatty acids as it carries them through the watery environment of the cell, but must then unfold to release them upon interaction with ACP-dependent enzymes. We believe that ACP is a special flexible and dynamic protein, with specific amino acids important for enzyme binding and triggering the unfolding and release of the acyl chain. Our main approach is to engineer defined amino acid replacements in ACP using site-directed mutagenesis; this provides information either by blocking ACP function with selected enzymes, or by introducing probes (eg. fluorescence) to track the binding and structural events at the molecular level. We also use a method called proteomics, which can rapidly identify and characterize new ACP partners among the thousands of proteins in a bacterial cell. As bacteria need fatty acids to survive and cause disease, our studies will provide insight into the design of antibiotics. Our research will also help understand how ACP-like proteins function in the synthesis of many natural products.