Group Members

Eli McDonald

Current Graduate Student

Bachelor in Chemical Engineering, Vanderbilt University, USA
eli.f.mcdonald [ at ] vanderbilt
Vanderbilt University - MBRIII 5140 Office Suite

Research Interests:

• membrane proteins
• protein-protein interactions
• protein folding
• molecular chaperones
• mass spectrometry
• proteomics

Co-mentored by Dr. Lars Plate (Plate Lab)

Project Description:

I study Cystic Fibrosis Transmembrane conductance Regulator (CFTR) protein folding, the causative gene in the monogenic, lethal disease Cystic Fibrosis (CF). CFTR is an apical membrane anion channel that folds in the endoplasmic reticulum and is trafficked to the plasma membrane. Patient mutations destabilized CFTR structure by perturbing efficiently tertiary and quaternary intramolecular assembly. Compared to wild type, the mutant protein has a higher affinity for molecular chaperones and other proteostasis factors that evaluate CFTR folding status and conjugate misfolded proteins for degradation. Hence, the mutant protein is degraded and not present in CF patients. My project explores the CFTR interactions with molecular chaperones using site directed incorporation of photochemical crosslinking unnatural amino acids. The goal is to determine which regions of the protein are destabilized by a mutation using computational structural biology methods, and then probe those regions by site specific crosslinking LC-MS/MS proteomics.