Defective ribosomes activate ribosome-associated quality control pathway

Maintaining cellular proteome integrity is crucial for normal cell functioning and survival as dysfunction to proteostasis gives rise to aging-related diseases. Cells have evolved a multitude of protein surveillance machineries to monitor the cytosol for aberrant proteins, including the ribosome-associated quality control (RQC) pathway which targets aberrant nascent chains at their birthplace. Characterisation of stalling-inducing aberrant transcripts has been the focus of most research in the last decade. In this FYP, however, I demonstrated that defects in ribosome itself can also trigger the RQC pathway. First, I analysed toxic effects of stall-inducing aberrant mRNAs. The observed toxicity prompted me to examine if genetic mutations for ribosomal proteins also display toxicity, reflecting increased ribosomal stalling. 19 ribosomal mutants were examined in this study to investigate relationship between ribosomal defects and the RQC pathway. I discovered that two yeast strains, deleted for ribosomal protein genes RPS1B and RPL24, display greater incidence of ribosomal stalling. Eukaryotic ribosomes consist of ~80 proteins and this study shows that mutations in those ribosomal proteins can lead to increased ribosomal stalling. Although molecular mechanisms underlying defective ribosome stalling remain to be elucidated, this study will expand our understanding of when and how the RQC pathway protects cells.Bachelor of Science in Biological Science

Extracellular vesicles and lipoproteins – Smart messengers of blood cells in the circulation

Abstract Blood cell‐derived extracellular vesicles (BCEVs) and lipoproteins are the major circulating nanoparticles in blood that play an important role in intercellular communication. They have attracted significant interest for clinical applications, given their endogenous characteristics which make them stable, biocompatible, well tolerated, and capable of permeating biological barriers efficiently. In this review, we describe the basic characteristics of BCEVs and lipoproteins and summarize their implications in both physiological and pathological processes. We also outline well accepted workflows for the isolation and characterization of these circulating nanoparticles. Importantly, we highlight the latest progress and challenges associated with the use of circulating nanoparticles as diagnostic biomarkers and therapeutic interventions in multiple diseases. We spotlight novel engineering approaches and designs to facilitate the development of these nanoparticles by enhancing their stability, targeting capability, and delivery efficiency. Therefore, the present work provides a comprehensive overview of composition, biogenesis, functions, and clinical translation of circulating nanoparticles from the bench to the bedside