Warren Rouse, a Biochemistry Ph.D. student in Professor Walter Moss’ research group has been awarded a five-year Ruth L. Kirschstein Predoctoral Individual National Research Service Award (F31). This award is to enable promising predoctoral students with potential to develop into a productive, independent research scientist while conducting graduate research. When congratulating Warren, Dr. Kristen Johansen, Professor and BBMB Department Chair, said to her knowledge, “this is the first F31 awarded in the department, and a very prestigious and competitive accomplishment.”
Along with Professor Moss, Warren will be co-mentored by Professor Matthew Disney at the Scripps Research Institute. Warren’s research will focus on expanding the druggable human genome to include RNA structural motifs that can bind small-molecule drugs. RNA, a single-stranded molecule encoded within our genome, plays a key role in gene expression and is implicated in most human diseases. The vast majority of drugs, however, target human proteins, which only constitute a tiny fraction of our genome. The protein coding portion of our genome constitutes only ~3% of total sequence, with only ~15% of these proteins being druggable (a fraction of a fraction). The vast majority of the genome (over 85%) is, however, transcribed into RNA. If only part of this RNA turns out to be druggable, this represents a massive reservoir of targets for next generation therapeutics.
To unlock this currently undruggable part of the human genome, Warren will integrate two pipelines established in each of his mentors’ labs. He will apply ScanFold, a bioinformatics program developed at ISU by the Moss Lab, to discover unusual structural elements in RNAs that have a high probability of functionality. These elements will then be evaluated via Inforna, a cheminformatics program developed by the Disney lab to predict small molecules that can strongly bind to specific RNA structures. Initial focus will be on the broad application of these tools to the human genome, with iterative homing-in on genes of exceptional interest to medicine: e.g., critical genes in cancer that have few effective drugs.
Warren said “growing up in a small town in Eastern Iowa, I never imagined that I would be spearheading a research project with such potentially global impact! I am grateful for the opportunities presented here at ISU and for the support offered by the Ruth L. Kirschstein Predoctoral award. This allows me to focus 100% on my research and I’m excited to make an impact!”. Professor Moss added that, “Warren’s research has potentially transformative reach in advancing a totally new way of treating disease. Modulating RNA biology with small molecules can have big impacts in how we deal with cancer, autoimmune disease and pathogenic infection. This research aims to tackle early questions essential in this process—how we discover good targets.”
Ruth L. Kirschstein Predoctoral Individual National Research Service Award will be funded through the National Cancer Institute, part of the National Institutes of Health; and, beginning in June of this year, will cover all costs associated with Rouse’s studies.