My name is Gabby Klemme, and I am a senior majoring in biochemistry at Iowa State University. At Iowa State, I work in a biochemistry laboratory with Dr. Eric Underbakke, studying scaffolded signaling complexes. Specifically, my project focuses on creating a fluorescence dye that can be used to identify a Halo tag when coupled to it. A Halo tag is a protein that forms a complex when bound to a molecule, and the complex is then used to bind to another protein that is of interest. Through my Halo protein expression system, I re-engineered a gene construct to allow for ample purification, so that I may have a pure source of Halo tag for testing. This summer, I am working at the Sanford Consortium for Regenerative Medicine in Dr. Evan Snyder’s laboratory. With Dr. Snyder and my mentor, Rus Nuryyev, we are focused on studying the biology of stem cells and their roles in the tissues involved in maintaining the body’s stable internal state, developmental biology, and recovery from injury and disease. However, our current research focus has shifted to studying the relationship between stem cells and SARS-CoV-2 with my project looking at neural stem cells and their connection to the SARS-CoV-2 route of entry.
As more COVID-19 cases arise involving patients with neurological symptoms, such as headaches and disturbed consciousness, understanding the relationship between this virus and the central nervous system (CNS) has become vital. The virus responsible for COVID-19, named SARS-CoV-2, enters cells through the binding of the spike (S) protein on the virus to the angiotensin converting enzyme 2 (ACE2) receptor on the host cell. SARS-CoV-2 could cause severe neurological injury, further justifying the need for a better understanding of the virus and the different cell types and body systems it can affect. Thus, my project will look at the relationship between SARS-CoV-2 and cortical interneurons and will establish how the virus enters these neurons to cause infection. Cortical interneurons are a type of neuron found in the brain and are involved in regulating other types of neurons called excitatory neurons. Cortical interneurons regulate or inhibit the number of signals that are sent throughout the brain and nervous system. However, when they malfunction, they are not able to control the excitatory neurons causing overstimulation which is linked to neurological diseases, such as schizophrenia and epilepsy.
Since we are seeing neurological symptoms with COVID-19 infections, I proposed that neurons in the human body express the ACE2 receptor which binds to the S protein on SARS-CoV-2, allowing the virus to enter and infect the cells. To identify how SARS-CoV-2 enters neurons, I grew a cortical interneuron brain organoid, or a simplified brain grown in the laboratory, and later infected it with the virus. Finally, through the use of a confocal microscope, I visualized the neurons, virus, and ACE2 receptor to determine the appropriate SARS-CoV-2 route of entry into neurons. The most significant impact of this project is that the results will allow us to gain a better understanding of SARS-CoV-2 and how it can cause the neurological symptoms that are becoming more common. Furthermore, determining the route of entry SARS-CoV-2 takes into neurons can help develop therapeutics that target and prevent the virus from entering.