Internal Seminar: Kamila Mustafina, Engineering Synthetic Riboswitches for Biomedical Applications

Internal Seminar

Speaker: Kamila Mustafina, PhD Student, Nucleic Acid and Chemistry Engineering Unit (Yohei Yokobayashi Unit)

Title: Engineering Synthetic Riboswitches for Biomedical Applications

Abstract:

Riboswitches are natural and artificial noncoding RNA elements capable of controlling gene expression in response to chemical signals without direct involvement of protein factors. One strategy for engineering synthetic riboswitches is to combine an aptamer –a short RNA sequence that specifically binds to a ligand– and a self-cleaving ribozyme to create an aptazyme whose self-cleavage activity is regulated by the aptamer ligand. These aptazymes can be embedded in the 3’UTR of mRNAs to chemically control gene expression in mammalian cells. This property of riboswitches opens a wide area of applications in biology and medicine. However, engineering riboswitches that function efficiently in mammalian cells remains challenging, partly due to the difficulties associated with generating and screening aptamers and aptazymes that function in the cellular environment rather than in test tubes.
The overall goal of my thesis research is to advance the riboswitch technology toward more practical applications. First, I plan to develop and improve aptazyme architectures as well as screening technologies that exploit deep sequencing to generate aptazymes that function efficiently in mammalian cells. In addition to working with the existing aptamers, I will also develop new aptamers against endogenous proteins and nontoxic small molecules with potential practical applications. Finally, I will use these aptamers, aptazymes, and screening methods to engineer riboswitches that function in mammalian cells to demonstrate potential applications in gene therapy and biological investigations.

Following the seminar, please join us for free pizza, soft drinks, and scientific discussion from 5-5:30pm.