Ep. 97: “Viral Structures” Featuring Dr. Erica Saphire
Jan 28, 2025
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Dr. Erica Saphire, President and CEO of the La Jolla Institute, specializes in viral immunity and pathogenesis. She shares insights on the groundbreaking capabilities of cryo-electron microscopy, revealing how it can illuminate viral fusion processes like those of the measles virus. Saphire also discusses her leadership role and highlights the importance of research in combating viral diseases. The conversation spotlights the evolution of antibody responses and the innovative use of AI in structural biology to tackle complex viral challenges.
Dr. Erica Saphire emphasizes the significance of cryo-electron microscopy in visualizing viral proteins, which enhances understanding for vaccine development.
The concept of T-cell exhaustion reveals the need for new strategies in cancer therapies by targeting early precursors of ineffective T-cells.
Collaboration among researchers is essential in immunology, facilitating breakthroughs in understanding infectious diseases and advancing therapeutic solutions.
Deep dives
Research on Viral Glycoproteins
Dr. Erica Sapphire's research primarily focuses on viral glycoproteins and their structural biology. This area is crucial because understanding the structure of viral proteins allows researchers to gain insights into how viruses interact with the immune system. Sapphire's early work included one of the first crystal structures of a human IgG antibody bound to an HIV receptor, highlighting the importance of structural biology in immunology. By employing advanced techniques such as cryo-electron microscopy, her team is able to visualize the complex interactions between viral proteins and antibodies, which is essential for developing effective vaccines and therapies.
The Significance of Cryo-Electron Microscopy
Cryo-electron microscopy (cryo-EM) has revolutionized structural biology by allowing scientists to visualize proteins in their native conformations. Unlike traditional x-ray crystallography, which requires proteins to form crystals that may not represent their functional states, cryo-EM captures proteins in a more physiological environment. This leads to a deeper understanding of the dynamic nature of proteins and their interactions, particularly in the context of viral infections. The ability to see proteins as they exist in real-world conditions enhances the development of vaccines and therapeutic strategies against various pathogens.
T-Cell Exhaustion and Immune Response
The concept of T-cell exhaustion is crucial in immunology, particularly in chronic infections and cancer. Research has shown that T-cells can lose their efficacy over time, limiting their ability to respond to infections or tumor cells. Recent studies indicate that exhausted T-cells have precursors formed early in the immune response, which was previously misunderstood. This new understanding underscores the importance of targeting T-cell exhaustion in cancer therapies and vaccine development to revitalize immune responses and improve patient outcomes.
ILC2s in Glucose Homeostasis
Innate lymphoid cells type 2 (ILC2s) have been identified as critical players in maintaining glucose homeostasis through their effects on glucagon secretion in the pancreas. During fasting, ILC2s migrate from the gut to the pancreas, where they help regulate blood glucose levels by producing necessary cytokines. This discovery highlights the intricate connections between the immune system and metabolic processes in the body. By understanding these relationships, targeted therapies could potentially be developed for metabolic disorders, such as diabetes.
Collaborative Research in Immunology
Collaboration among researchers is highlighted as a vital component of advancing immunology and related fields. Joint efforts can lead to significant findings, particularly in understanding and treating infectious diseases and cancer. For instance, large-scale studies that bring together previously competing labs have led to breakthroughs in antibody research and therapeutic interventions. Such collaborative endeavors not only enhance the data pool but also inspire innovative solutions to complex problems in immunological research.
Dr. Erica Saphire is President and CEO of La Jolla Institute. Her research explains, at the molecular level, how and viruses are pathogenic and provides the roadmap for medical defense. She talks about the capabilities of cryo-electron microscopy and how it can help illuminate the mechanisms of measles viral fusion. She also discusses her role leading La Jolla Institute. (36:45)
ILC2s in Pancreatic Cancer – IL-33 induced tertiary lymphoid structures in a mouse model of pancreatic ductal adenocarcinoma. (4:35)
Precursors of Exhausted T Cells – Precursor T cells with at least two distinct phenotypes are preemptively generated regardless of infection outcome. (9:10)
T Cells in Chronic Infections – A population of stem-like CD8+ T cells can adapt their differentiation trajectory to either an acute or chronic viral infection. (10:45)
ILC2 Migration in the Gut – Researchers identified a role for immune cells in regulating blood glucose levels in mice. (29:13)
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