Research

Understanding how cellular proteins maintain their correct conformation is a current problem in cell biology. How is the one-dimensional genetic information transformed into three-dimensional protein structures with biological activity? Many proteins can exist in more than one conformation and many proteins must change conformation (and activity) regularly. The precision and efficiency with which protein conformational states are regulated are essential to the life of the cell.

In neurons, there are significant demands on cellular folding events. Complex interactions between multiple cellular components underlie synaptic transmission, a process that occurs with speed, precision, high fidelity and plasticity. Cellular accumulation of incorrectly folded proteins is the molecular basis of several diseases. Huntington’s, Alzheimer’s, Parkinson’s and Creutzfeld Jacob’s/mad cow diseases are caused by defects in protein folding in neurons, underlining the biological importance of this problem.  A network of proteins molecular chaperones regulates cellular protein folding. We study the specialized network of molecular chaperones that regulate conformation of synaptic proteins and how this network goes wrong in neurodegeneration.  Recently our efforts are centered on molecular chaperones that facilitate cargo loading into extracellular vesicles for export to recipient cells. These extracellular vesicles are a double edge sword as they are known to transport both functional folded proteins and misfolded toxic proteins between cells. 

Research in the Braun lab is focused on the molecular and cellular basis of chaperone function with respect to synaptic transmission. Our research will provide both conceptual and detailed mechanistic information describing how molecular chaperones regulate protein conformation at the synapse and how targeting chaperone networks can provide therapeutic strategies. These research interests have led us to develop a multifaceted approach in which molecular biological, biochemical, cellular and physiological techniques have been incorporated.