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Study to explore molecular mysteries of protein-RNA droplets

Human cells consist of spherical droplets that play vital roles in cellular processes. These spherical droplets, called protein-RNA condensates- forms after proteins and RNA can cluster together.

However, how these droplets come together remains unclear. It remains obscure what molecular forces govern their composition, and what drives them to take on a liquid state, or a harder, more gelatinous form?

UB biophysicist Priya Banerjee will explore these questions through a Maximizing Investigators’ Research Award (MIRA) for outstanding investigators from the National Institute of General Medical Sciences, part of the National Institutes of Health.

This study is expected to improve the comprehension of cellular processes that impact human health.

Protein-RNA condensates are involved in a variety of biological functions. In cells, they can take the form of membrane-less organelles (MLOs) to help organize the internal contents of cells and serve as hubs of biochemical activity, recruiting molecules needed to carry out essential cellular functions, including gene regulation.

Banerjee explains, “Additionally, MLOs can be involved in human disease. For example, liquid droplets holding a protein called “fused in sarcoma” are found in healthy brain cells. But in some patients with the neurodegenerative disease amyotrophic lateral sclerosis (ALS), the protein forms aggregates of solid material.”

Banerjee, along with his team, is developing a toolbox to study the behavior of protein-RNA condensates. The toolbox combines correlative multicolor single-molecule fluorescence microscopy, dual-trap optical tweezers, and microfluidics.

Scientists will also evaluate how these condensates may change under conditions associated with the disease, such as the presence of a genetic mutation that creates an altered protein sequence. If successful, they would ultimately apply its novel approach to target abnormal protein-RNA droplets associated with human diseases pharmacologically.

Banerjee says, “MLOs play key roles in intracellular storage and signaling processes, and are associated with many human diseases. There is a clear gap in our understanding of the molecular driving forces responsible for the physiologic regulation of their composition and the forces that facilitate their pathologic transformations. This is partly due to the lack of suitable tools that can simultaneously probe the structure, dynamics, and rheological properties of the biomolecular​ condensates across different length- and time-scales.”

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