Maria Barna, Ph.D.

Research

We are exploring a new code for gene regulation at the level of ribosomes—the cell’s protein-making machinery—in guiding development of specific cells and tissue within an embryo. For every gene that becomes active, the information contained in its DNA is converted into a molecule of RNA, which is then “read” by ribosomes to make the proper protein. Within a given organism, scientists assumed that all ribosomes were essentially the same and that they exert largely rote-like functions, but I have discovered that ribosomes in different embryonic cells and tissues include distinct components and, as a result, are specialized for producing particular proteins. Now, my laboratory will delineate the differences in ribosome composition and activity in the various tissues of the developing mouse embryo. We will also investigate how these “specialized ribosomes” select which RNAs they will translate into proteins, by defining the sequences and/or structures within RNAs that interact with ribosome components. This work will reveal the role that ribosomes play in decoding how the genome is expressed in time and space during development, and could shed light on birth defects and human disease that are associated with mutations in ribosomal components.

As an Innovation Fund investigator, Maria Barna, Ph.D., is teaming up with Christine Dunham, 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.