Christine M. Dunham, Ph.D.

Research

Our laboratory is interested in the structural basis of regulation of the ribosome, a large RNA-protein macromolecular machine. Translation dysregulation leads to a variety of disease states, and because the ribosome is also an important antibiotic target, understanding the basic molecular mechanisms that govern ribosome function is both fundamentally important and biomedically relevant. Our interests include the controlled regulation of protein synthesis when exposed to stressors including antibiotic exposure and the roles of toxin-antitoxin pairs in inhibiting protein synthesis to alter bacterial physiology. Our approach is to obtain 3D “snapshots” of the process using structural biology approaches in combination with biochemical, cellular, and microbiological techniques to understand the molecular basis of ribosome regulation.

As an Innovation Fund investigator, Christine Dunham, Ph.D., is teaming up with Maria Barna, Ph.D., to identify and understand how small molecules increase global protein synthesis. Such increases can ameliorate the effects of various human diseases, but the underlying mechanisms are unknown, and there are no pharmacological approaches to increasing protein synthesis. The pair plans to investigate a vast library of compounds to identify those that enhance protein synthesis, unravel their mechanisms of action, and evaluate their effects in disease models such as amyotrophic lateral sclerosis, also known as ALS, and Diamond Blackfan Anemia (DBA). The project combines the strengths of both labs: Barna’s expertise in omics technologies for translational control and in animal models, and Dunham’s extensive experience in the mechanistic dissection of ribosomal molecular activity. These comprehensive studies could shed light on the mechanisms by which small molecules upregulate global protein synthesis and point the way toward novel approaches to combat human disease by reprogramming the ribosome.