Scott Bolton

Current Research Interests:

Targeted Drug Delivery for Bladder Cancer Project

The goal of this project is to deliver ligands by intravesical therapy to bladder cancer cells by targeting the fibronectin/integrin receptor internalization pathway. Fibronectin Attachment Protein peptide fragments are synthesized and conjugated to polyethylene glycol (PEG) structures that facilitate binding and internalization of the ligand. A cytotoxic or immunotherapeutic molecule is attached as cargo and is released from the structure during endocytosis. Both in-vitro (mouse cell line) and in-vivo (mouse) efficacy will be measured. The benefits of this strategy include: direct synthesis of the ligand using biocompatible components, smaller size, and less off-target interactions than existing methods.

Single Particle Reconstruction Project

The goal of this project is to determine the structure of proteins by affinity grid capture and electron microscopy (EM). The protein of interest is co-expressed along with N-myristoyltransferase in E. Coli resulting in a protein functionalized with 12-azidododecanoic acid at the N terminus. A lipid monolayer containing phospholipids conjugated with PEG and "click chemistry" tail are assembled on a Langmuir trough and transferred to an electron microscopy grid. Proteins are then depisited on the grid and click to the monolayer in random orientations. EM images of these covalently attached proteins are acquired and software reconstruction methods will generate the 3-D shape of the protein. The benefits of this method include covalent attachment of the protein of interest, a potential reduction of preferred orientations, and an improved retention of wild type functionality.

Selected Publications:

 TBA.