Carolyn E. Machamer, Ph.D.

Research

We are interested in the structure and function of the Golgi complex, a ubiquitous eukaryotic organelle that plays a central role in post-translational processing and sorting of newly synthesized proteins and lipids in the secretory pathway. Towards this goal, we are studying the targeting and function of resident Golgi proteins. We are interested in the contribution of the lipid bilayer to targeting of transmembrane Golgi proteins, and in the function of a group of peripheral Golgi membrane proteins called golgins. The golgins are thought to play an important role in Golgi structure and in vesicle trafficking. We recently found that golgin-160 is a substrate for caspase cleavage during programmed cell death (apoptosis). We believe that specific apoptotic signals are transduced at Golgi membranes, and that cleavage of golgin-160 may be critical for downstream signaling events. In non-apoptotic cells, golgin-160 is involved in trafficking of specific cargo molecules, including the beta-1-adrenergic receptor, and the insulin-regulated glucose transporter, GLUT4.The other research interest in the lab is the assembly mechanism of coronaviruses, enveloped viruses that bud into Golgi compartments. Coronaviruses are vertebrate pathogens that usually cause mild respiratory or gastrointestinal disease. However, the recent emergence of severe acute respiratory syndrome (SARS), which is caused by a novel coronavirus, has sparked much interest in this group of viruses. We are addressing how coronaviruses target their envelope proteins to Golgi membranes, and how they interact with each other at the virus assembly site. We are also exploring how coronaviruses are exocytosed after they bud into the Golgi lumen. Our long-term goal is to understand the advantages of intracellular assembly for coronaviruses. A better understanding of intracellular assembly and the mechanism of exocytosis should lead to novel strategies for antiviral therapeutics.