Frontiers Of Biology

The Role of Synthetic Biology in Discovering the Signaling Pathway of Circadian Rhythms

Synthetic biology has an increasingly important role in today’s molecular biology research due to the tools it provides scientists. Through the use of DNA manipulation and formation of various genetic circuits, details about various biomolecular mechanisms have been discovered. With these genetic circuits and assays, Dr. Luo and Dr. Sehgal were able to investigate the role miRNAs play in the mechanism controlling the output component of the Drosophila circadian rhythms. Prior research has shown that miRNAs–small, noncoding pieces of single-stranded RNA–have major roles in controlling regulation after transcription or translation has occurred. They accomplish this by binding to specific sites on a gene and silencing the expression of that gene. Because the entire clock mechanism within flies relies on various regulatory feedback loops, research has shown that miRNAs also play a role in regulating the circadian cycle by blocking gene expression at different points to correspond with the natural 24-hour cycle of most biological processes or to respond to certain stimuli, such as light.

Using Synthetic Biology to Understand Circadian Rhythms

Luo and Sehgal were able to study how miRNAs interacted with the pathways associated with the circadian pathways by using different vectors that controlled the expression of a certain gene. With these genetic circuits, the researchers were able to determine the various effects upon the output mechanism of the pathway. They were able to identify miR-279 as one of the miRNAs that affected the flies’ ability to control locomotor activity on a temporal basis. Through overexpression of silencing of the gene that produce miR-279, it was determined that this miRNA directly affected the output mechanism in which biological processes were controlled by specific genes within that mechanism. Furthermore, this specific miRNA was not controlled by the central clock component that many other miRNA behaviors are controlled by. MiR-279 was proven to affect the Upd gene, which in turn affects the JAK/STAT pathway. As this pathway affects protein synthesis and regulation, miR-279 was proven to affect the rhythms of biological processes within the flies. Though the report only describes a recent development in the study of circadian rhythms, it represents one of the many discoveries in this field, and in the future, may help treat conditions that affect the circadian pathway of an organism.

To get a scientist’s perspective on the experiment presented in the report by Luo and Sehgal, I interviewed Dr. Christine Marshall-Walker. Dr. Marshall-Walker is a biology teacher at Phillips Academy and has a past in neurobiological research. She also oversees a group of students at Phillips Academy conducted their own research studies in molecular biology and guided me during my senior year through my own research project. Dr. Marshall-Walker has discussed how research has always been the most interesting part of science. Through the accumulation of data and validating results, working as a scientist has never felt like an occupation. In regards to the paper, Dr. Marshall-Walker reinforced the importance of synthetic biology as a useful way to manipulate gene expression and view the effects these changes make. She believes that Luo and Sehgal were able to efficiently approach each experiment in the report with the use of synthetic biology and logically proceed through the experiment, linking each part of the pathway to miR-279. She concludes by discussing how closely related the human circadian pathway is to that of the flies being studied due to shared orthologs of genes. Because of this relationship, the experiments conducted on the Drosophila circadian pathway could possibly tell what roles molecules have in our own rhythmic pathways.

The importance of maintaining circadian rhythms has been shown in many studies. Because many cyclical biological processes rely on proper circadian rhythms, understanding the mechanism behind how an organism controls this process has become growing field in biomolecular research. As miRNAs have shown the ability to regulate these temporal cycles, research has also increased with regard to their role in the process as well as the manipulation of their effect. As Luo and Sehgal have shown, the path through which an miRNA can affect the circadian output mechanism proves their importance to this process as well as how many benefits could come from further research in this field.