Research
Translation—the final step of the central dogma—is one of the most fundamental processes underlying all life. In this process, the genetic code encoded in mRNA is converted into amino acids, forming the basis of protein synthesis. Although translation has long been regarded as a classical and well-understood biochemical reaction, recent technological advances have begun to reveal a wealth of phenomena that cannot be explained by traditional textbook models.
By leveraging cutting-edge analytical approaches, we aim to uncover the dynamic processes through which nascent polypeptide chains, produced by translation, mature into fully functional proteins.
“Deciphering the Precision Design of Macromolecular Complexes”
The intracellular environment is a “chaotic” world, densely packed with countless molecules that are constantly colliding with one another. Yet within this apparent disorder, macromolecular complexes are assembled with remarkable precision and order.
Representative molecular machines such as ribosomes and proteasomes are often depicted in textbooks as fully assembled structures. However, many aspects of their biogenesis remain unresolved. In particular, increasing attention has recently been directed toward the “individuality” of these complexes. While it has long been suggested that subtle variations in their components may lead to functional differences, the true nature of this diversity has remained elusive. We aim to explore this uncharted territory and uncover the fundamental design principles governing the assembly and function of macromolecular complexes.
“Uncovering the Origins of Aging: Molecular Mechanisms of Translational Stalling and Breakdown of Quality Control”
The maintenance of protein homeostasis (proteostasis) is a fundamental survival strategy that underpins all biological activity. Recent studies have revealed that, with aging, there is a significant increase in ribosome stalling during translation, leading to the accumulation of aberrant proteins. Errors at the level of translation, followed by the formation of protein aggregates, are increasingly recognized as critical risk factors in the pathogenesis of age-related neurodegenerative diseases such as Alzheimer’s disease. Despite these advances, the molecular mechanisms underlying the age-dependent acceleration of translational stalling and the accumulation of defective protein products remain largely unknown. Cells are equipped with sophisticated quality control systems that detect and resolve translational abnormalities; however, how these surveillance mechanisms become impaired or altered during aging remains a black box.
We focus on the dynamics of quality control factors we have uniquely identified, aiming to elucidate the entire process—from the origin of translational stalling to the accumulation and aggregation of its aberrant products—within the context of aging.
“From Multi-omics to Single-Molecule Analysis: Integrating Technologies to Probe the Depths of Life”
To dissect complex biological phenomena, we employ a multifaceted approach that transcends any single scale of analysis. We integrate multi-omics strategies—including RNA-seq, Ribo-seq, and proteomics—to capture a comprehensive view of cellular processes. At the same time, we establish advanced in vitro reconstitution systems to rigorously examine the behavior of individual molecular components. Prepared samples are further analyzed using high-speed atomic force microscopy (HS-AFM) and cryo-electron microscopy (cryo-EM), enabling us to visualize the dynamics and structures of macromolecular complexes at single-molecule resolution. The fusion of “macroscopic overview” and “microscopic validation” defines the core strength of our research.