Wednesday Nite at the Lab
press release: For the fall semester, WN@TL goes hybrid both with Zoom and with in-person presentations. The zoom registration link is still go.wisc.edu/240r59. You can also watch a live web stream at biotech.wisc.edu/webcams
On March 30 Robert Kirchdoerfer of Biochemistry will be here to share his insights into the virus that causes covid, and ways to exploit those insights to impede infection and reduce disease. His talk is entitled "Molecular Biology of Coronaviruses."
Description: Coronaviruses are pathogens of both animals and humans. This family of viruses circulates with diverse reservoirs of viruses in animal populations. Periodic transmission of a coronavirus from an animal host to a human host with subsequent human-to-human transmission resulting in outbreaks of novel coronaviruses in the humans. The 21st century has seen three of these crossover events. SARS-CoV emerged in 2002 and was quickly contained using public health measures. MERS-CoV emerged in 2012 and continued animal-to-human transmission events have continued to the present day. Finally, SARS-CoV-2 emerged in 2019 to spur the global COVID-19 pandemic. Over the decades, we have learned a lot about how coronaviruses enter cells and replicate their RNA genomes. These studies were key preparations for the rapid development of SARS-CoV-2 vaccines and antiviral therapies.
Coronaviruses enter host cells using large viral spike proteins. As part of their entry process, these spikes undergo large conformational changes to recognize host cells and fuse viral membranes with host cell membranes. Atomic models derived from cryo-electron microscopy studies were key to understanding these conformational changes and lead to the design of spike-like proteins to elicit better antibody responses. These designed spike-like proteins have been incorporated into several popular COVID-19 vaccines including those offered by Pfizer, Moderna and Johnson & Johnson.
After entering host cells, a coronavirus must replicate and transcribe its viral genome to produce new viral proteins and viral genomes. Coronaviruses carry their genomes as single pieces of RNA. As host cells do not have a polymerase capable of copying an RNA template, the virus supplies its own polymerase. In coronaviruses, these polymerases form large protein-protein complexes to combine several enzyme activities and co-factors. High-resolution imaging using electron microscopes has shown us how the polymerase accepts substrates for genome transcription and replication. These studies are also starting points for understanding how antiviral drugs like remdesivir and molnupiravir, approved for the treatment of COVID-19, interact with viral proteins and inhibit viral replication.
Bio: Dr. Robert Kirchdoerfer, Ph.D., grew up in Oregon, Wisconsin before attending college at the University of Wisconsin-Madison where he studied Genetics and Biochemistry. He received his Ph.D. working with Ian Wilson at the Scripps Research Institute in La Jolla, California studying the replication of influenza virus. Dr. Kirchdoerfer’s postdoctoral work, also at the Scripps Research Institute focused on the replication of Ebola virus and the cellular entry and replication of coronaviruses. He joined the faculty of University of Wisconsin-Madison in 2019 as a member of the Biochemistry Department, the Institute for Molecular Virology and the Center for Quantitative Cell Imaging where he continues to carry out high-resolution imaging of coronavirus proteins.
Explore More:
Kirchdoerfer Lab website: https://kirchdoerferlab.wisc.
SARS-CoV-2 Life cycle animation: https://coronavirus-
US Center for Disease Control: https://www.cdc.gov/
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