Ariel Bazzini, Ph.D., cannot recall a time when he did not play soccer during his childhood in Buenos Aires, Argentina. “I started kicking the ball as soon as I learned how to walk,” he says. “Like most kids in Argentina, I dreamed of playing for the national team.”
At the age of 15, Bazzini began having another dream -- about becoming a scientist. His interest in science was sparked by his middle school biology teacher’s lectures about the Human Genome Project. “I love genes and studying how they work, and how their functions impact life,” says Bazzini, who received a Ph.D. in molecular biology in 2007 at the University of Buenos Aires. For his doctoral dissertation, he studied plant genetics in the laboratory of Sebastian Asurmendi, Ph.D., at the Institute of Biotechnology in Argentina’s National Institute of Agricultural Technology (INTA).
Prior to joining Stowers as an assistant investigator in 2016, Bazzini was a postdoctoral fellow and subsequently an associate research scientist in the laboratory of Antonio J. Giraldez, Ph.D., in the Department of Genetics at Yale University. Bazzini’s current focus on the regulation of gene expression in vertebrates originated during his time at Yale.
Image: Courtesy of Dr. Ariel Bazzini
Bazzini’s contribution to this research field has included the first clear demonstration of the kinetics of microRNA (miRNA) molecules in the in vivo regulation of gene expression in the zebrafish model system. Bazzini and his Yale collaborators determined that during early embryogenesis in zebrafish, miRNA regulates gene expression and thereby protein production by first repressing the translation of mRNA molecules and then triggering the molecules’ decay.
These findings, reported in the journal Science in 2012, provided some of the first evidence that “at a certain point of development and cell differentiation, very strong gene regulation can occur at the level of translation without any change of the mRNA level,” Bazzini says. Thus, if the researchers had used mRNA levels during embryogenesis as the sole indicator of gene regulation, they would have incorrectly concluded that the genes were not regulated, he adds.
For several decades, most studies of gene expression were focused on the process of transcription. More recently, post-transcriptional regulation caught the attention of several groups, and in particular the regulatory elements in the 3’UTR. For example, microRNAs are master regulators of gene expression at the post-transcriptional level that mainly recognizie elements in the 3’UTR, Bazzini says.
Bazzini’s research has revealed that the translation process also plays a fundamental role in regulating gene expression in vertebrates (The EMBO Journal in 2016). “The findings have changed the way that coding regions are viewed. The coding region is the longer region of the transcript that contains regulatory information layered on top of which amino acids are encoded. This research has also opened the question of how the ribosome affects mRNA stability and gene expression,” says Bazzini.
Image: Courtesy of Dr. Ariel Bazzini
The cellular processes of transcription and translation are very complicated, Bazzini points out. There is tremendous gene-to-gene variation in not only the stability, or half-life, of mRNA molecules but also the amount of protein synthesized during translation, he says. “Why are some mRNA molecules so poorly translated and others so efficiently translated? And, why are some mRNA molecules so stable and others so unstable? I am very intrigued by these questions,” he adds.
In another study with zebrafish as the model system, Bazzini and collaborators uncovered several hundred translated small open reading frames (smORFs) in genes previously regarded as non-coding RNAs. These smORFs were detected through the use of ribosomal profiling technology, which allows direct quantification of ribosome footprints. The findings of this study significantly increased the number of known vertebrate genes that encode micropeptides, proteins that have less than 100 amino acids.
“While the function of a few of these micropeptides has been shown, most of them remain uncharacterized,” says Bazzini. The research also revealed that a gene could contain more than one ORF, he adds. In the study, he and his collaborators identified numerous coding smORFs in the 5' untranslated region (5’ UTR) of mRNAs. These findings were published in The EMBO Journal in 2014.
With the Institute’s physical resources and the expertise of the scientific staff, Bazzini says he has the flexibility to choose the most fitting model organism, from self-generating flatworms to zebrafish to mice, for his particular research questions. And he looks forward to jumping into projects he has yet to imagine.