2024 Seed Grant
Rebecca M. Voorhees, Ph.D.
California Institute of Technology
The function of the brain relies on an intricate network of connections that mediate the transfer of information throughout the central nervous system. At the molecular level, communication relies on proteins that are embedded into the thin waxy envelope that encapsulates and protects individual cells, known as the plasma membrane. These ‘membrane proteins’ regulate many fundamental functions of the central nervous system including sensing stimuli such as odors and pain, as well as responding to neurotransmitter levels to modulate our emotions. Given their diverse and important roles, dysregulation of membrane protein levels and activity is associated with many diseases of the central nervous system including neurodegeneration, depression, and addiction. Further, over 50% of drugs currently in clinical use bind and target a membrane protein.
To function correctly, membrane proteins must be correctly embedded within the membrane during their synthesis. Because the brain relies on many specialized membrane proteins that are only made in highly specific cell types, the machinery for their synthesis is not yet well defined. Here we propose to identify and characterize the factors required for the synthesis, folding, and assembly of membrane proteins in the human brain. Understanding the molecular basis for this process will provide the tools and knowledge needed to manipulate membrane protein function to treat disease.
