Researchers previously developed a structurally aligned ribosomal RNA (rRNA) database referred to as the Full-Length Organismal rRNA Alignment (FLORA) database. Building on that database the research team plans to further investigate a computational approach for analysis of the FLORA database to contain full length rRNA sequences from each domain of life. This analysis identifies conserved nucleotide elements (CNEs) in rRNA from each domain of life. Also, this analysis identifies the CNEs that are universally conserved in all domains and those that are domain specific (highly conserved in one domain but degenerate in the other two domains of life).
Analysis of the database may assist with identifying new sites in rRNA as targets for the development of new antibiotics for use in humans, animals and plants. The computational approach presented here to identify rRNA targets for new antibiotics is a creative new way to approach antibiotic design and has the potential to be transformative to the field of drug development.
The NSF Innovative Corps (I-corps) provided us with a training program on how to commercialize research funded by previous NSF support. Our I-corps team consisted of Susan Gerbi (Principal Investigator), Raphyel Rosby (Entrepreneurial Lead) and Patrick McHugh (Business Mentor). The focus of our team was to explore commercialization of our NSF-funded research on ribosomal RNA (rRNA). In that project, we developed the Full-Length Organismal rRNA Alignment (FLORA) of rRNA sequences aligned according to their secondary structure. The FLORA database drew rRNA sequences from the three domains of life (eukaryotes, bacteria, archaea). Using bioinformatic analyses, we identified the Conserved Nucleotide Elements (CNEs) in each domain of life. Then we compared the CNEs between the three domains. Some CNEs were universally conserved in all three domains, and included some universal sequences previously known, thus validating our approach. Some of the universal CNEs had not been identified before and provide regions of crucial importance to the ribosome for future study. In addition to the universal CNEs, we also discovered CNEs that are fully conserved in one domain of life but degenerate in sequence in the other two domains. Of special interest for this grant application were two CNEs that are fully conserved in all bacteria but degenerate in eukaryotes (and in archaea), thus providing excellent new targets for the design of new antibiotics. It was this finding that we wanted to commercialize. The I-corps program was very work-intensive, but well worth the effort as we learned so much about how to commercialize our findings. Through customer interviews that we conducted as part of the I corps program, we learned that it is premature at this point to form a start-up company. However, the steps necessary to do so were outlined and we are pursuing that path for future commercialization of our NSF-funded research. Moreover, we have filed a patent application on our work to protect the intellectual property. The NSF I-corps program definitely met its stated goals.
