What is Membrane Biology?
Membranes surround the outside of cells, as well as the individual organelles in eukaryotic cells, such as the ER, Golgi, nucleus, mitochondria and endosomes/lysosomes. These bilayers are composed of phospholipids, cholesterol and proteins. They form a selectivity barrier to prevent unregulated movement of molecules in and out of these compartments, and protect the cell from outside perturbations. Movement of macromolecules between the different intracellular organelles is facilitated by small membrane-bound vesicles. Movement of smaller molecules, such as sugars or ions, is facilitated by transporters and channels in the membrane. Numerous proteins and sugar molecules present in the lipid bilayer, or that are associated with the bilayer, are responsible for transport of specific molecules, cellular recognition, signaling, and immune responses. Inappropriate functioning of these pathways can lead to devastating human diseases.
Our research in the area of Membrane Biology
Studies of membrane biology in the Biochemistry and Molecular Pharmacology (BMP) department reflect the complicated nature of studying these intriguing macromolecular structures. Our research is very interdisciplinary, taking advantage of a wide range of techniques and ideas. The Carruthers’ lab uses biochemical and biophysical approaches to study how glucose transporters function. In the Munson lab, they use a variety of biochemical/structural and genetic/cell biological studies to elucidate the mechanisms of vesicular transport into and out of cells.
Similar combinations of approaches guide research in the Gilmore lab on post-translational modification of proteins by glycosylation. The Kobertz lab uses chemical biology to investigate the regulation and function of ion channels in the plasma membrane, while the Munson lab studies export of mRNAs across the nuclear membranes.
Our breakthrough discoveries
Together, the research in BMP has gained remarkable insights into the mechanisms underlying membrane transport, vesicular trafficking, and nuclear export. The Carruthers’ lab used homology scanning mutagenesis across the family of facilitative glucose transporters to identify critical sequence determinants of transporter oligomeric structure and catalytic function. In the
Gilmore lab, they elucidated how asparagine linked glycosylation of proteins in mammalian cells is catalyzed by two different oligosaccharyltransferases (STT3A and STT3B complexes) that respectively mediate cotranslational glycosylation of the nascent polypeptide as it passes through the protein translocation channel, or posttranslocational glycosylation of acceptor sites that have been skipped by the STT3A complex. The Kobertz lab is using the membrane (glycocaylx) to visualize cellular efflux from ion channels and membrane transporters. The Munson lab determined the molecular architecture, protein-protein interactions and functions of several highly conserved eukaryotic proteins that regulate membrane targeting and vesicle fusion.