$2M NIH Grant Supports Work Into Cell Structures Linked to ALS Protein Clumps
A $2 million grant from the National Institutes of Health (NIH) is funding work to better understand how molecular structures called protein-RNA condensates form and are regulated within cells.
Findings from the five-year project could help in understanding and treating diseases where these molecular structures play a role, including amyotrophic lateral sclerosis (ALS).
Given by the NIH’s National Institute of General Medical Sciences, the grant was awarded to Priya Banerjee, PhD, a biophysicist and professor at the University of Buffalo, in the form of a Maximizing Investigators’ Research Award, a university news story reported.
Protein-RNA condensates, as the name suggests, are droplet-like structures composed of proteins and RNA molecules, or the intermediate molecules generated from DNA that work as a templates for protein production.
Within cells, these condensates can act as membrane-less organelles (MLOs). Essentially, they act as a hub for biochemical activity within cells, recruiting molecules needed to carry out cellular functions (e.g., gene regulation), and they help organize the internal content of cells.
While MLOs have important roles in healthy cell activities, they are also involved in disease. For example, in healthy brain cells, droplets containing the protein fused in sarcoma (FUS) are present in a liquid state. However, in the brains of some ALS patients, this protein forms aggregates of solid material that may contribute to disease progression.
The exact biochemical processes that govern the normal behavior of protein-RNA condensates are unclear — and so are the factors that cause these condensates to behave in ways that drive disease.
Banerjee, through the grant award, aims to better understand these processes.
“MLOs play key roles in intracellular storage and signaling processes, and are associated with many human diseases,” he said. “Currently, there is a clear gap in our understanding of the molecular driving forces that are responsible for physiologic regulation of their composition, and the forces that facilitate their pathologic transformations.”
Partly, this is “due to the lack of suitable tools that can simultaneously probe structure, dynamics and rheological [deformation and flowing] properties of the biomolecular condensates across different length- and time-scales,” Banerjee added.
His team is developing a “toolbox” to aid in studying MLOs, combining specialized microscopes with technology that allows the researchers to manipulate the molecules with great precision, namely dual-trap optical tweezers and microfluidics. Then, this toolbox will be used to learn more about the behavior of protein-RNA condensates, both in healthy cells and in the context of disease.
Ultimately, this research may unveil new approaches to targeting the abnormal protein-RNA droplets associated with ALS and possibly other diseases.
“The NIH award will enable us to address some critical gaps in knowledge over the next five years,” Banerjee said.