The Diamond Blackfan Anemia Foundation (DBAF), in partnership with DBA Canada (DBAC), is proud to provide a $25,000 grant to Dr. David Bodine for his project, Assay Development and Preliminary Screening of Small Molecules to Increase Ribosomal Protein Levels.
David Bodine, PhD, Senior Investigator and Chief, Genetics and Molecular Biology Branch Head, Hematopoiesis Section of the National Human Genome Research Institute explained, “The vast majority of DBA patients are heterozygous for mutations in a ribosomal protein gene. That means that they have one mutated gene that usually does not make any protein, and one normal gene that makes perfectly good ribosomal protein mRNA that is translated into ribosomal protein. We asked: ‘Why can’t the healthy ribosomal protein gene make up for the loss of the mutated gene’s output?’ After all, in many other diseases, like sickle cell disease and cystic fibrosis, heterozygous people are quite normal and healthy.
The answer is that the beginning of ribosomal protein RNAs have a special sequence that controls their translation. We have designed a cell line that uses the beginning of a ribosomal protein mRNA attached to an easy-to-use reporter gene. We are collaborating with the National Center for Accelerating Therapeutics (NCATS) to use our reporter cell line to test hundreds of thousands of potential drugs to see which ones can increase the translation of ribosomal protein mRNA.
So far, we have shown that we can get good signals from a few hundred cells growing in individual wells on a plate that has over 1500 wells. These 1500 well plates are about the size of a dollar bill and hundreds of these plates can be put through the robotic screening system in a week.”
DBAF and DBAC are grateful to our families, friends and supporters that allow us to continue to fund important DBA research projects. We appreciate Dr. Bodine’s interest in DBA and all his efforts. Dr. Bodine added,
“The money supplied by the DBA Foundation and DBA Canada will support a student who will work full time with NCATS to optimize the screening assay and to test potential therapeutic compounds that are identified in the drug screen. We are very excited about the prospects for this research and we are proud that the DBAF and DBAC are helping us to make the work go faster.”