FSU Researcher Awarded $1.8M by NIH to Investigate Fibrotic Process

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by Steve Bryson PhD |

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Research examining the role that protein-RNA interactions play in promoting pulmonary fibrosis (PF) and other related conditions is being accelerated by a $1.8 million grant from the National Institutes of Health (NIH).

The funding, granted to Robert Silvers, PhD, a Florida State University (FSU) assistant professor of chemistry and biochemistry, will help detail how La-related proteins, called LARPs, interact with and regulate RNA function. RNA is the molecule that serves as a template for the creation of proteins.

One of these proteins, known as LARP6, is associated with the development of fibrosis, or tissue scarring. But how these proteins bind to RNA at the atomic level — and how this relates to the onset of the disease — is unknown.

“The gap of knowledge in understanding the protein-RNA interactions on an atomic level is a big roadblock for the development of therapeutic strategies to combat diseases such as fibrosis,” Silvers said in a university press release.

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Fibrosis occurs when scar tissue replaces healthy tissue due to the excessive production of a connective tissue protein called collagen.

In PF, scarring causes lung tissues to stiffen and harden, leading to respiratory symptoms such as shortness of breath and a dry, hacking cough. Fatigue, weight loss, and muscle and joint pain are other common symptoms of pulmonary fibrosis. Scarring also can occur in other organs, particularly the liver.

The LARP6 protein helps regulate collagen production by binding to its messenger RNA, which carries instructions for making the protein. Compounds that block LARP6 activity have been shown to have antifibrotic effects.

Revealing the molecular details of LARP-RNA interactions can help with the design of potent therapeutics that suppress collagen production and can ultimately slow or halt scar tissue formation.

“The binding of LARP6 to this RNA is a critical step in the development of fibrosis (excessive scarring) of various organs, such as liver, lungs, kidneys, heart, skin, etc.,” said Branko Stefanovic, PhD, professor of biomedical sciences at the FSU College of Medicine, who is collaborating with Silvers and has extensive experience investigating fibrosis.

“Fibrosis has no cure and knowing the structure will enable the design of inhibitors as specific antifibrotic drugs,” Stefanovic added.

Silvers will use a research technique similar to MRI, known as nuclear magnetic resonance (NMR) spectroscopy, which is available at the National High Magnetic Field Laboratory and the department of chemistry and biochemistry, with headquarters at FSU.

NMR spectroscopy takes advantage of the magnetic properties of the atomic nucleus to sense the environment that surrounds each atom. This can reveal the atom-by-atom molecular structure of the LARP-RNA interaction.

“We’ll be looking at protein-RNA interactions using NMR spectroscopy, a method related to Magnetic Resonance Imaging (MRI) that generates detailed three-dimensional images of tissues and organs,” Silvers said.

“In a similar fashion, NMR spectroscopy will allow us to visualize the molecular map of the entire protein-RNA complex with atomic-level precision. We can visualize where every single atom will be,” he added.

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