Robert Kirchdoerfer

EDUCATION

PhD – The Scripps Research Institute, United States

RESEARCH SUMMARY

We examine molecular events in viral lifecycles particularly those of coronaviruses. We use biochemistry and structural biology to study virus entry and RNA replication.

RESEARCH DETAIL

Coronaviruses use a large spike glycoprotein to recognize host receptors and fuse the virion membrane with the host cell membrane to initiate infection. These spike proteins are also the target of neutralizing antibody responses and form the key component of many human coronavirus vaccines. We use binding-studies, in vitro evolution and cryo-electron microscopy to examine the consequences of receptor binding or antibody binding to the viral spike. We are particularly interested in the evolution of spike stability to undergo large conformational changes in response to receptor binding.

Upon entering host cells, the viral genome is translated to produce a polyprotein that is cleaved into 16 non-structural proteins (nsp). These non-structural proteins are responsible for replicating and transcribing the viral genome through the modification of ER membranes and the formation of a multi-subunit RNA replication complex. We use biochemistry, biophysics, virology and structural biology to explore the interactions among these nsp to understand how many viral enzymes and co-factors work together to carry out viral RNA synthesis. Our goal is to identify new targets for antiviral drugs.