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David Bartel (Birmingham, 1958) is a leading researcher in molecular and cell biology who has made significant contributions to the field of microRNAs. His work has been instrumental in understanding the biology of miRNAs and their importance in gene regulation. Bartel is known for his work in identifying miRNAs and elucidating their role in inhibiting gene expression, initially studying the ability of RNA to catalyse reactions and more recently focusing on microRNAs and other regulatory RNAs. Since 2000, his laboratory has made fundamental discoveries about the genomics, biogenesis and regulatory targets of these RNAs, as well as the molecular and biological consequences of their actions in animals, plants and fungi.
Bartel graduated from Goshen College with a degree in Biology. Shortly after completing his PhD at Harvard University in 1993, he joined the Whitehead Institute as a fellow. Bartel is currently a Professor of Biology at the Massachusetts Institute of Technology, a Whitehead Institute Fellow and a Howard Hughes Medical Institute Investigator.
Bartel’s many contributions to our understanding of RNA function have been recognised with numerous awards, including the NAS Molecular Biology Award and his election as a member of the National Academy of Sciences.
microRNAs and practical applications
MicroRNAs (miRNAs) are small non-coding RNA molecules that play a crucial role in the regulation of gene expression in organisms. Their main function is to control the amount of proteins produced from genes by binding to specific messenger RNAs and suppressing their translation or promoting their degradation.
This ability to regulate genes makes them promising targets for disease therapy. Therapies based on miRNAs can be developed to modulate the expression of genes involved in diseases such as cancer, cardiovascular diseases, neurodegenerative diseases and metabolic disorders. These therapies may include the administration of artificial miRNAs to increase or decrease the expression of specific genes to restore homeostasis and treat disease at the molecular level, or the use of anti-miRNAs that control miRNAs already produced by the body itself.
Our partner Arthex Biotech is developing such oligonucleotides within the OLIGOFASTX project aimed at treating Fuchs’ Corneal Endothelial Dystrophy and Cachexia Cancer.
Discovery of miRNAs and the role of David Bartel
miRNAs were discovered in the 1990s independently by two groups of researchers. Victor Ambros and his team initially identified the miRNA lin-4 in the nematode C. elegans, while David Bartel and his lab discovered miRNAs in the plant Arabidopsis thaliana and demonstrated their ability to regulate genes. These pioneering findings laid the foundation for understanding miRNAs as small RNA molecules that play an essential role in regulating gene expression, which has led to extensive research into their function and their potential in the diagnosis and treatment of disease.
The Bartel lab’s discoveries were a crucial breakthrough in understanding the diversity and importance of miRNAs in gene regulation in eukaryotic organisms. Bartel and his team then conducted further research to determine how miRNAs bind to specific mRNAs and how they inhibit protein translation or promote mRNA degradation, providing valuable insights into the underlying mechanisms of action of miRNAs.
David Bartel has been widely recognised for his contribution to the understanding of miRNAs and has received several awards and honours for his work, including the Breakthrough Prize in Life Sciences in 2012. His research continues to be fundamental to the field of molecular biology and gene regulation.
Photos: Gretchen Ertl/Whitehead Institute (left) and Ryan Jeffs/Wikipedia (right)
Use of new technologies for the study of miRNAs
David Bartel’s lab runs a miRNA database called TargetScan, available to all scientists from the Massachusetts Institute of Technology (MIT) in the US.
This tool provides a better understanding of how miRNAs can influence gene regulation and how this may be related to biological processes and diseases. It is therefore of particular interest for identifying potential miRNA targets in functional genomics studies and may help in the investigation of miRNA-based therapeutics and in understanding gene regulatory networks.
TargetScan uses algorithms and databases to identify miRNA binding sites in the 3′ untranslated regions (UTR) of gene-specific messenger RNAs (mRNAs). These binding sites are areas where miRNAs can interact with mRNAs and potentially regulate their expression. The tool considers factors such as sequence complementarity and RNA secondary structure to make accurate predictions about which genes may be regulated by a given miRNA.
In summary, some of the key findings on David Bartel’s role in miRNAs include:
- Discovery and characterisation: Bartel and his team conducted pioneering research that led to the identification and characterisation of miRNAs in different organisms, such as Arabidopsis thaliana and others. His work was instrumental in establishing the existence and importance of these small RNA molecules in gene regulation.
- Mechanisms of action: Bartel contributed significantly to the understanding of how miRNAs work. Their research helped reveal the mechanisms by which miRNAs bind to specific messenger RNAs and regulate gene expression, either by inhibiting protein translation or promoting mRNA degradation.
- Broad influence: Bartel’s work served as the basis for subsequent research on miRNAs in a variety of species, including humans, and sparked a great deal of interest in the identification of miRNAs and their function in biological processes and disease.
- Tools and resources: His work also resulted in the development of bioinformatics tools such as TargetScan, which are widely used to predict potential targets of miRNAs in genomes, which has facilitated research in this field.
All these contributions have paved the way for further research and highlighted the importance of miRNAs in cell biology and the development of potential therapies for various diseases.
Sources
Header image: https://wi.mit.edu/news/david-bartel-honored-french-academy
Lewis, B. P., Shih, I. H., Jones-Rhoades, M. W., Bartel, D. P., & Burge, C. B. (2003). Prediction of mammalian microRNA targets. Cell, 115(7), 787-798.
Bartel, D. P. (2004). MicroRNAs: genomics, biogenesis, mechanism, and function. cell, 116(2), 281-297.
Lewis, B. P., Burge, C. B., & Bartel, D. P. (2005). Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. cell, 120(1), 15-20.
Agarwal V, Bell GW, Nam J, Bartel DP. Predicting effective microRNA target sites in mammalian mRNAs. eLife, 4:e05005, (2015). eLife Lens view.
Garc\EDa DM, Baek D, Shin C, Bell GW, Grimson A, Bartel DP. Weak Seed-Pairing Stability and High Target-Site Abundance Decrease the Proficiency of lsy-6 and Other miRNAs. Nat Struct Mol Biol., 18:1139-1146 (2011).
Friedman RC, Farh KK, Burge CB, Bartel DP. Most Mammalian mRNAs Are Conserved Targets of MicroRNAs. Genome Research, 19:92-105 (2009).
Grimson A, Farh KK, Johnston WK, Garrett-Engele P, Lim LP, Bartel DP. MicroRNA Targeting Specificity in Mammals: Determinants beyond Seed Pairing. Molecular Cell, 27:91-105 (2007).
Lewis BP, Burge CB, Bartel DP. Conserved Seed Pairing, Often Flanked by Adenosines, Indicates that Thousands of Human Genes are MicroRNA Targets. Cell, 120:15-20 (2005).