Shwachman-Bodian-Diamond syndrome (SDS) is a rare autosomal recessive disease that affects ribosomal biogenesis resulting in bone marrow failure. Patients with SDS have an increased likelihood of developing several severe health complications, including acute myeloid leukemia. It has a poor prognosis and the only curative treatment available is hematopoietic stem cell transplant. SDS is caused by inherited mutations in the SBDS gene. SBDS regulates the 60S ribosomal machinery that is critical for synthesizing proteins in cells. SBDS modulates 60S function by aiding in the release of eukaryotic translation initiation factor- eIF6 from the ribosome. Recent studies have identified somatic heterozygous mutations in the eIF6 gene that are predicted to compensate for SBDS loss and yield a better prognosis for SDS progression. In order to better understand the mechanism of this disease development, it is necessary to study the role of disease-implicated eIF6 mutations and how they contribute to SDS progression. Through site-directed mutagenesis, we introduced two key mutations in yeast eIF6. These recombinant mutant proteins will be purified to assess eIF6 function and activity through biochemical studies. These findings will advance our knowledge to understand the mechanism of SDS progression, and development of future therapeutic interventions.

Zephyr would like to thank her faculty sponsor, Dr. Sofia Origanti, for their support of this project and Dr. Robert Pampel for the nomination to present her work.