My name is Murial Ross, and I am a rising senior at Santa Clara University majoring in Bioengineering with a Biomolecular focus. At my university, I am working in Dr. Prashanth Asuri’s laboratory to explore the impact of hydrogel stiffness on human stem cells. There are many different types of hydrogels, each made up of a polymer that forms a gel that can retain water, similar to a sponge. Hydrogels are commonly used for wearable devices, like contact lenses, or provide 3D scaffolds for cells to grow. Researchers are exploring how altering properties of hydrogels, like stiffness, can impact toxicity of compounds to stem cells. By replicating stiffnesses of tissues, one could accurately gauge toxicity of a compound to that tissue type. Due to the online academic format in spring 2020, I have been remotely researching journal articles and writing segments for a review in the scientific journal Polymers on the use of nanoparticle-reinforced hydrogels in biomedical applications. The incorporation of nanoparticles, like clay or metal, can greatly improve and add new properties to hydrogels, enabling their use in applications like wound healing or drug delivery. This summer, I have been working in Dr. Evan Snyder’s laboratory at the Sanford Consortium for Regenerative Medicine through the SRF Summer Scholars Program. Dr. Snyder is the current Director of the Center of Stem Cells and Regenerative Medicine at Sanford Burnham Prebys Medical Discovery Institute. The laboratory focuses on stem cell research in the brain and lungs to provide insights on developmental biology, maintenance of optimal internal conditions in a healthy adult and recovery from injury. In response to the COVID-19 pandemic, the laboratory has created and infected organoids to explore the virus’s impact on the body in addition to testing drugs against COVID-19.
My internship project focused on the impact of COVID-19 infection on the secretion of surfactant protein B (SP-B) in the brain. Surfactant is a mixture of lipids and proteins, used by the lungs to reduce surface tension to prevent lung collapse and to provide anti-inflammatory properties. Surfactant in the brain was recently discovered in 2013 by Stefan Schob and collaborators at the University Hospital Leipzig in Germany although its role in disease is still unknown. Based on Schob et al. ‘s research, SP-B is secreted in the choroid plexus of the brain, where cerebrospinal fluid (CSF) is produced, potentially explaining its presence in the CSF. CSF serves as a shock absorber to protect the brain, in addition to circulating nutrients and removing cellular waste products from the brain. Schob et al. believes SP-B has similar anti-inflammatory properties in the brain as it does in the lungs. In a clinical study, they demonstrated that the concentration of SP-B changes in response to neural inflammation due to infections or cerebral infarction, defined by an area of necrotic tissue due to a blockage or narrowing of the arteries that supplies blood and oxygen to the brain. In addition, they know surfactant decreases surface tension of bodily fluids, indicating a disturbance in SP-B could disrupt CSF flow and could cause neurological diseases.
As more patients contract COVID-19, doctors have noticed some patients develop neurological symptoms ranging in severity from loss of smell and taste to encephalitis or acute cerebrovascular disease in the form of ischemic stroke or cerebral hemorrhage, both a type of brain bleeds. Many of the severe neurological symptoms are caused by neural inflammation or disrupt CSF flow. I hypothesize SP-B is upregulated in response to COVID-19 infection to counterbalance the detrimental effects of the immune system. A clinical study in Wuhan, China determined that 36% of patients presented with neurologic symptoms. Those that had severe COVID-19 infections were significantly older and were more likely to have more severe neurological symptoms. SP-B could play a role in the severity of COVID-19 related neurological symptoms. May et al. demonstrated that elderly patients produced significantly less CSF than younger patients. Since CSF production is decreased in elderly patients, I hypothesize that the SP-B secretion is also decreased in older patients, but further study would be needed. The severity of COVID-19 neurological symptoms in older patients could be linked with the decrease in SP-B, limiting the body’s natural anti-inflammatory response and regulation of CSF flow, therefore increasing the severity of symptoms.
For my project, I generated two types of brain organoids and infected them with a COVID-19 pseudovirus to analyze COVID-19’s impact on SP-B secretion. The pseudovirus has the same spike protein as the SARS-CoV-2, allowing the pseudovirus to imitate SARS-CoV-2 infection without the dangers of handling the live SARS-CoV-2 virus. I hypothesize there will be an increase in SP-B secretion from infected organoids compared to non-infected organoids, emphasizing that SP-B plays an immunological role in the brain and could impact the severity of neurological symptoms in older patients with SP-B deficiencies.