DoID Adhoc Seminar
Biography: Dr. Luo Dahai obtained his Bachelor of Science (BSc) degree in 2006 and completed his Ph.D. in 2010, both from Nanyang Technological University (NTU), Singapore. Following his doctoral studies, he pursued postdoctoral research from 2010 to 2013 at the Howard Hughes Medical Institute (HHMI) and Yale University, USA. He returned to NTU as a Nanyang Assistant Professor at LKCMedicine, where he served from 2013 to 2019. In 2019, he was promoted to Associate Professor, a position he currently holds at LKCMedicine, NTU, Singapore.
Research Interests: Our lab is dedicated to investigating the molecular interactions between RNA viruses and their human hosts. We utilize a diverse range of scientific approaches, including biochemistry, biophysics, structural biology, and cell biology, to delve into this critical field. Our research has provided significant insights into the mechanisms of viral replication and the complexities of host defense systems. These studies are not merely academic pursuits but essential steps toward a deeper understanding of viral-host dynamics.
Our long-term goal is to expand knowledge of host-pathogen interactions, a foundation crucial for developing more effective antiviral strategies and improving human health. By comprehensively analyzing these interactions, we aim to contribute to the advancement of medical science and address one of the most enduring challenges in global health, ultimately enhancing human well-being.
Presentation Statement: Positive-sense RNA viruses replicate their genomes within specialized, membrane-associated organelles that coordinate RNA synthesis, processing, and export while evading host innate immunity. Using Chikungunya virus as a primary model, this talk presents an integrated mechanistic framework for alphavirus replication complex assembly and function, with extensions to other positive-sense RNA viruses. Recent structural and biochemical studies reveal that the alphavirus replication complex is organized by a membrane-anchored nsP1 oligomer that scaffolds the viral RNA-dependent RNA polymerase nsP4 and associated factors into a confined reaction environment. Within this assembly, polymerase activity emerges through co-folding and multivalent interactions rather than as an intrinsic property of the isolated enzyme, enabling regulated transitions between distinct replication states. Structural evidence further supports defined pathways for RNA template entry, elongation, and product export, indicating that viral RNA synthesis is vectorial and spatially coordinated. These processes are modulated by membrane curvature, protein stoichiometry, and dynamic conformational changes that collectively govern the establishment, activation, and output of the replication organelle. Comparative analyses across (+)RNA viruses highlight conserved principles, including membrane remodeling, multi-component polymerase complexes, and sequestration of double-stranded RNA intermediates, alongside divergent architectural strategies that shape replication efficiency and immune evasion. These insights provide a conceptual basis for therapeutic intervention, including targeting replication complex assembly, exploiting structural constraints for nucleoside analogue incorporation, and modulating virus-induced membrane environments, while also informing the rational design of attenuated viruses and self-amplifying RNA platforms for next-generation vaccines.
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