Nobel Prize Highlights microRNA Discovery: Insights for INL Nanosafety Work
October 10, 2024
The 2024 Nobel Prize in Physiology or Medicine has been awarded to Victor Ambros and Gary Ruvkun for their groundbreaking discovery of microRNA and its role in post-transcriptional gene regulation.
This pivotal advancement in molecular biology and epigenetics was made through studies on the microscopic worm C. elegans, showing how microRNAs regulate gene expression by binding to messenger RNA (mRNA) and preventing protein production. Their discovery has far-reaching implications across biology, medicine, and toxicology—including key research initiatives at INL.
Within the Research Group focused on Nanosafety, INL researchers utilise C. elegans as a model organism to assess the potential health risks of particulate matter and nanomaterials. Just as Ambros and Ruvkun’s findings have transformed our understanding of gene regulation, our work is expanding the boundaries of toxicological research by employing functional genetics, toxicogenomics, and epigenetic biomarker evaluations to study the impacts of nanomaterials.
C. elegans: A Nobel-Winning Model for Toxicology Research
The 2024 Nobel Prize further validates the use of C. elegans in toxicology research. Its simplicity, genetic transparency, and short life cycle make it an invaluable tool for studying complex biological processes. Importantly, C. elegans shares many genetic pathways with humans, enabling researchers to draw relevant connections between nanomaterial exposure and potential human health risks. The model also aligns with the 3Rs principles (Reduction, Refinement, and Replacement), supporting ethical alternatives to mammalian testing, and has been recognised by the US FDA as a valuable New Approach Methodology (NAM) for toxicological studies.
At INL, our research involves various assays designed to observe phenotypic outcomes—such as survival, growth, reproduction, and neurobehavioural changes—following exposure to nanomaterials. These outcomes provide critical insights into the potential toxic effects of these materials. However, we also complement these phenotypic observations with molecular-level research, including the study of microRNA expression patterns, directly reflecting the relevance of the Nobel-winning discovery.
Exploring the Role of microRNA in Nanotoxicology
Building on Ambros and Ruvkun’s breakthrough on microRNA’s role in gene regulation, INL is exploring how microRNA expression is altered after C. elegans is exposed to nanomaterials and particulate matter. Supported by the EU-funded projects LEARN and iCare, INL aims to profile global microRNA changes in C. elegans to better understand the molecular mechanisms behind nanomaterial-induced toxicity. This profiling will reveal how nanomaterials may disrupt normal cellular functions by altering gene expression, potentially leading to health issues such as neurodegeneration and cancer.
Integrating microRNA expression analysis into our toxicological studies enhances our ability to pinpoint toxicity mechanisms at the molecular level. As Nivedita Chatterjee, researcher leading the Molecular Toxicology Research Line at INL, explains: “Our research at INL is strongly aligned with the discoveries recognised by the 2024 Nobel Prize. MicroRNA profiling allows us to uncover critical molecular changes in response to nanomaterial exposure, helping us understand toxicity at its root. By combining functional genetics with epigenetic biomarkers, we can bridge the gap between observed biological effects and the underlying molecular mechanisms.”
Leveraging AI for Advanced Data Analysis in Nanotoxicity Research
In addition to molecular insights, the development of new methods for analysing large volumes of data is accelerating progress. According to Ernesto Alfaro, Group Leader of the Nanosafety Group at INL, “the new methods for analysing large volumes of images—essentially vast amounts of data—will enhance our understanding of the C. elegans model and the regulation of gene expression by miRNAs. This advancement highlights the necessity of using artificial intelligence to recognise changes, modifications, and alterations. This is particularly intriguing in light of the 2024 Nobel Prize in Physics, which focuses on AI and neural networks.”
This AI-driven approach can complement our microRNA research by offering enhanced data analysis capabilities. By recognising subtle changes in gene expression patterns, we can further refine our understanding of nanomaterial-induced toxicity and its implications for human health.
Future Directions in Nanosafety and Molecular Toxicology
As the field of epigenetics continues to evolve, INL remains at the forefront of nanotoxicology research.
As we continue to explore the intersection of nanotechnology and molecular biology, our work promises to yield new discoveries that will enhance our understanding of environmental toxicology and human disease.