Ep. 83: “Biomolecular Sensors” Featuring Dr. Shana Kelley
Jul 16, 2024
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Dr. Shana Kelley, President of the Chan Zuckerberg Biohub Chicago and professor at Northwestern University, discusses her pioneering work on reagentless biosensors that track molecular interactions without additional reagents. She explores the innovative application of DNA-based systems in detecting binding events, enhancing immunology research. Kelley also shares insights into balancing her scientific career with family life, along with humorous anecdotes about navigating teenage adventures and the mysteries of pet behavior.
Dr. Shana Kelley highlights the development of reagentless biomolecular sensors, crucial for real-time monitoring of inflammatory disorders in living organisms.
Recent findings on Mycobacterium tuberculosis ATP synthase structure aid drug design, potentially improving treatment efficacy against multi-drug resistant TB strains.
Research into B7H4's role as an immune checkpoint molecule reveals its significance in fetal immune tolerance and implications for cancer therapy.
Deep dives
Exploring Biomolecular Sensors for Inflammatory Disorders
Dr. Shayna Kelly discusses her innovative research on biomolecular sensors that aim to address inflammatory disorders. These sensors are designed to be reagentless, allowing for their potential implantation in living organisms, including humans. This technology is crucial as it removes the need for continuous reagent addition, which can complicate measurements in vivo. The development of these sensors can pave the way for real-time monitoring of immune responses, contributing significantly to the field of immunology.
Advancements in Tuberculosis Treatment Research
Recent research has focused on tuberculosis (TB) and the role of innovative drug design in combating this persistent infection. The study revealed important structural differences between the Mycobacterium tuberculosis ATP synthase and that of humans, informing the binding mechanisms of two key drugs: bedaquiline and TBAJ587. This distinction allows for better targeting of the drugs, potentially reducing toxicity and resistance development. Discovering the drug interactions at the molecular level is essential for developing therapies that can effectively treat multi-drug resistant TB strains.
Research into Toll-like receptors (TLRs) has revealed the dynamic nature of the MyD88 adaptor protein, critical for TLR signaling. The study identified that MyD88 forms specialized complexes called mydosomes that cluster proteins necessary for effective signaling after TLR activation. These mydosomes are dynamic, coalescing upon receptor stimulation and disassembling after approximately 30 minutes. This research provides valuable insights into the spatial organization of immune signaling and how innate immune responses are regulated.
Investigating the Role of B7H4 in Immune Tolerance
The role of B7H4 as an immune checkpoint molecule has gained attention, particularly in the context of pregnancy and cancer. Research indicates that B7H4 contributes to immune tolerance, allowing for fetal development despite immunological challenges. Experiments involving B7H4 knockout mice demonstrated increased fetal reabsorption, highlighting the protein's protective role during pregnancy. This finding may have implications for cancer therapies by better understanding the mechanisms of immune tolerance in oncogenesis.
Nasal Tau Immunotherapy for Neurodegenerative Diseases
Innovative research explored the use of nasal tau immunotherapy to address intracellular tau accumulation, a major factor in neurodegenerative diseases like Alzheimer's. This approach involves a monoclonal antibody that targets misfolded, toxic tau proteins, enabling them to be cleared from neurons. By delivering the antibody intranasally, researchers effectively bypassed the blood-brain barrier, demonstrating improved cognitive functions in treated mouse models. This method not only shows promise for tau pathology but also emphasizes the importance of targeted delivery systems in neuroimmune therapies.
Dr. Shana Kelley is the President of the Chan Zuckerberg Biohub Chicago and the Neena B. Schwartz Professor of Chemistry and Biomedical Engineering at Northwestern University. The Kelley research group works in a variety of areas spanning bio analytical technology development and has pioneered new methods for tracking molecular and cellular analytes with unprecedented sensitivity. She talks about developing DNA-based reagentless biosensors and commercializing new technologies.
Onco-Fetal Immune Tolerance – Scientists cross-analyzed single-cell RNA sequencing data from human cancer types and the maternal-fetal interface to identify an onco-fetal immune tolerance checkpoint.
Tau Immunotherapy – Scientists loaded tau antibodies into micelles and administered them intranasally in mice.
