Horowitz Lab Awarded $1.8M Grant for Biophysics Research in Aging-Related Diseases

Funded in part through a new NIH Maximizing Investigator’s Research Award (MIRA) grant, the Horowitz Lab project is investigating how nucleic acids are involved in protein aggregation and folding. Protein misfolding and aggregation lead to many debilitating illnesses, including Alzheimer’s disease. The Horowitz lab recently found that nucleic acids can have strong chaperone activity to prevent protein aggregation and aid protein folding. Given their preponderance in the cell and strong effects on protein folding and aggregation, it is highly likely that nucleic acids are important players in protein homeostasis.

The work described in this proposal lays out studies to provide our first understanding of the basic principles by which nucleic acids modulate protein folding and aggregation, and thus protein homeostasis. The Horowitz’s Lab’s current investigations are directed at addressing two critical aspects:

1. Understanding the roles of chaperone nucleic acids in the cell.
2. Understanding the molecular mechanism of chaperone nucleic acids.

These studies utilize an interdisciplinary approach combining molecular biology, biochemistry, biophysics, and bacterial genetics. The preliminary data indicates that both the activities of nucleic acids to prevent and promote oligomerization are highly sequence dependent and are especially encoded for by quadruplex structures. These results help explain the biophysical causes of several neurodegenerative diseases. This insight also gives us the opportunity to control and study protein aggregation using specific nucleic acid sequences and structures.

The goal of the MIRA funding option is to increase the efficiency of National Institute of General Medical Sciences (NIGMS) funding by providing investigators with greater stability and flexibility, thereby enhancing scientific productivity and the chances for important breakthroughs. A recently introduced mechanism that distributes funding among the nation’s highly talented and promising investigators, NIGMS intends to largely replace single PI R01 grants with MIRA awards moving forward. The award Dr. Scott Horowitz received is for his research project, Nucleic Acids Roles in Protein Folding and Aggregation, totaling $1,841,445 in funding for 5 years, and is the first MIRA award received by a University of Denver researcher.