Mytochondria

Below are several annotated bibliographies I wrote for the Brown Precollege course Characterizing C. Elegans Using Reverse Genetics.

Myriam Lai

June 27, 2025

Fire, A., Xu, S., Montgomery, M. K., Kostas, S. A., Driver, S. E., & Mello, C. C. (1998). Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature, 391(6669), 806–811. https://doi.org/10.1038/35888

This study introduced the phenomenon of RNA interference (RNAi) in C. elegans, demonstrating that double stranded RNA (dsRNA) could specifically and potently silence gene expression. The researchers showed that injecting dsRNA corresponding to targeted genes resulted in phenotypes that mimicked loss of function mutations. Notably, the interference was far more effective than injecting either strand alone, suggesting a mechanism beyond simple antisense hybridization. The effects were gene specific, dose dependent, and heritable in the progeny. The findings laid the foundation for RNAi as a powerful genetic tool across multiple organisms and revolutionized functional genomics by enabling targeted gene silencing with high specificity and efficiency. This article is a foundational and credible scientific contribution to molecular biology, especially in the field of gene regulation. It was published in Nature, a leading peer reviewed journal, and the research was conducted by respected scientists in the field, including Nobel Prize recipients Fire and Mello. The experimental design is rigorous, the results are replicable, and the paper has been cited extensively. Its objectivity and clarity make it a reliable source. Compared to later studies, it is more exploratory but remains the essential starting point for understanding RNAi. This source is essential to my research on gene silencing technologies and their applications. It helps establish the biological basis for RNA interference, a method now used widely in genetic research, therapeutics, and biotechnology. By understanding the original mechanisms uncovered by Fire et al., I can better explain how RNAi evolved as a research and clinical tool. It also shapes my argument by showing how a simple discovery in a model organism can have profound, broad reaching implications. This article has deepened my understanding of how dsRNA functions in gene regulation and reinforced the importance of model organisms in biomedical breakthroughs.

Kern, Andreas, Natalie Spang, Heike Huesmann, and Christian Behl. “Novel Modulators of Proteostasis: RNAi Screen of Chromosome I in a Heat Stress Paradigm in C. elegans.” Cells, vol. 7, no. 6, 2018, p. 49. https://doi.org/10.3390/cells7060049.

This study investigates the cellular mechanisms of proteostasis using a large scale RNAi screen targeting chromosome I genes in Caenorhabditis elegans. The authors used a heat stress model to identify genes whose knockdown resulted in increased misfolding of a LUC::GFP reporter protein in muscle cells. Out of 2,875 genes tested, 185 were found to be genetic modifiers of proteostasis. Many of these genes were further validated in a C. elegans model expressing PolyQ35::YFP, an aggregation prone protein associated with Huntington’s disease. The authors also identified human orthologs of these genes and linked several to neurodegenerative diseases such as Alzheimer’s. The results emphasize the complexity of the proteostasis network and highlight novel candidates that may play crucial roles in maintaining protein homeostasis under stress conditions. This peer reviewed article offers a comprehensive and well executed investigation into genetic contributors to proteostasis. Published in Cells, a reputable open access scientific journal, and authored by experts in molecular biology and neurodegeneration, the study demonstrates high reliability. The methods—especially the use of RNAi, heat stress models, and protein aggregation assays—are rigorous and reproducible. Compared to earlier foundational work like Fire and Mello’s 1998 RNAi paper, this study applies RNAi to a functional screen for disease relevant pathways, showing the maturity and applicability of the method. Its integration of bioinformatics tools (WormBase, DAVID, Ensembl) adds depth to the analysis, especially regarding human disease relevance. The article maintains an objective tone and contributes useful data for both basic biology and translational research. This article is highly relevant to my research on the genetic regulation of protein folding and its implications for neurodegenerative disease. It provides a rich list of candidate genes that influence proteostasis, many of which are conserved in humans. This is particularly helpful in forming hypotheses about human disease pathways, especially those related to aging and Alzheimer’s. The methodology offers a template for how I might structure my own screen or validate hits from similar studies. Moreover, the study’s connection between basic C. elegans biology and human health issues illustrates how model organisms can be effectively used in translational research. It has expanded my understanding of the interplay between heat stress, chaperones, and degradation pathways in proteostasis maintenance.

López-Otín, Carlos, Maria A. Blasco, Linda Partridge, Manuel Serrano, and Guido Kroemer. “The Hallmarks of Aging.” Cell, vol. 153, no. 6, 2013, pp. 1194–1217. https://doi.org/10.1016/j.cell.2013.05.039.

This influential review article outlines nine “hallmarks” that define the biological aging process: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. Each hallmark represents a set of molecular and cellular events that contribute to the progressive functional decline observed in aging organisms. The authors argue that these features are not isolated but interconnected, forming a complex network that governs the aging phenotype. Importantly, the review emphasizes that amelioration of these hallmarks can potentially extend healthspan and lifespan, and it establishes criteria for identifying a hallmark of aging, such as being experimentally reversible and observable during natural aging. The article integrates findings across model organisms and human biology, offering a unified conceptual framework for aging research. This article is one of the most cited and comprehensive resources in the field of aging biology. Authored by leading experts and published in Cell, a top tier peer reviewed journal, it is a highly reliable and objective synthesis of current knowledge. The review not only summarizes existing research but also proposes a new organizational model that has since become foundational in the field. Compared to individual studies that focus on specific aspects of aging, this article stands out for its breadth and integrative perspective. It has influenced both basic research and therapeutic development, including efforts to target specific hallmarks pharmacologically. The information is well supported by evidence and broadly applicable, making it a useful and credible source. This article is pivotal to my understanding of aging as a multifactorial and interconnected process. It provides a valuable framework that helps categorize and relate various molecular mechanisms involved in aging. For my research, the hallmarks offer a roadmap to explore how interventions might delay aging or mitigate age related diseases. I plan to use this source as a theoretical foundation, both to define aging biologically and to justify the selection of experimental targets. It has significantly shaped how I think about the aging process—not as a single event, but as a systemic decline rooted in specific, targetable mechanisms.