How sea creatures’ superpowers inspire smart biomaterials for human health

Major discoveries about the inner workings of a fragile star’s ability to reversibly control the flexibility of its tissues will help researchers solve the riddle of mutable collagenous tissue (MCT) and potentially inspire new “smart” biomaterials for applications in human health.

The work is led by Denis Jacob Machado, assistant professor of bioinformatics at the Center for Computational Intelligence for Predicting Health and Environmental Risks at the University of North Carolina at Charlotte (CIPHER), and Vladimir Mashanov, a scientist at the Wake Forest Institute for Regenerative Medicine.

In “Unveiling putative modulators of mutable collagen tissue in the brittle star Ophiomastix wendtii: an RNA-Seq analysis,” published recently in BMC genomicsresearchers describe the advanced use of transmission electron microscopy (TEM), RNA sequencing, and other bioinformatics methods to identify 16 potential MCT modulator genes. This research represents a major advance in the precise understanding of how echinoderms rapidly and radically transform their collagenous tissue. The paper’s first author, Reyhaneh Nouri, holds a Ph.D. student in the Department of Bioinformatics and Genomics at UNC Charlotte.

“We are discovering the precise instructions that DNA sends to the cell: what it says, when it says it, and in what quantities. Think of DNA as the captain of a ship, giving orders to navigate and operate in “The RNA is the crew, diligently receiving those orders and carrying them out to ensure the ship’s mission is accomplished. We look at what the crew does and learn from their hard work,” explained Jacob Machado.

This advanced research aimed at identifying relevant molecular processes in an echinoderm could potentially open new doors to regenerative therapies in humans.

Echinoderms, such as brittle stars (a cousin of starfish and sand dollars) and sea cucumbers, possess remarkable abilities to adapt their body tissues in response to stressors and rapidly changing conditions, including detaching important parts of their body to escape predation or other dangerous situations. . Certain species of brittle stars are particularly suited to providing researchers with a viable test case for isolating MCT modulatory genes, which are the specific molecular instructions determining emerging tissue changes.

The new findings aim to shape the future development of smart, dynamic collagen-based biomaterials to treat human health problems, for example by helping wounds heal faster or providing alternative materials for tissue regeneration that do not trigger no immune rejection.

Jacob Machado and his colleagues at UNC Charlotte have already filed a provisional patent on the building blocks of what would be considered a revolutionary collagen-based biomaterial, which would be developed by industry. However, several key steps remain in the research.

“It starts with daring to try something completely new without knowing if it’s going to work or not,” said Jacob Machado.

The published research examines a clear genomic relationship between juxtaligamental fragile star cells (JLC) and reversible collagen modulation, identifying 16 different genes that represent an important and exciting “question mark,” said Jacob Machado.

In future research, using techniques such as in situ hybridization (ISH) and RNA interference (RNAi) to “hunt down” these genes, Jacob Machado said the team could study “what happens to echinoderms once some of these genes are deactivated.

This process of genomic detection and elimination will allow the team to determine whether putative MCT genes “are involved in specific functionalities of mutable collagen tissues,” according to Jacob Machado, who expects the next step in the research is completed over the next year and a half.

Pathway to a new collagen matrix and biomaterial

So far, according to Jacob Machado, the research merges multidisciplinary expertise with creativity and advanced bioinformatics. Jacob Machado credits the work of experts intimately familiar with bioinformatics and echinoderm biology, collaborating with an “extremely competent” team using transition electron microscopes, forming an imaginative team approach to “experimental designs” for RNA analysis.

Led by Jacob Machado and Mashanov, the UNC Charlotte Department of Bioinformatics and Genomics research team includes Nouri, April Harris, Gari New, William Taylor (student and staff), Daniel Janies and Robert W. Reid (professor ).

While the modulation of echinoderm collagenous tissues is familiar to scientists, the average beach hunter, and hungry fish, the team’s research puts science on an accelerated path toward understanding cellular tissue regeneration.

In BMC genomicswrite the researchers, “the study is the first attempt to discover novel echinoderm MCT-specific genes using state-of-the-art sequencing, differential gene expression, and annotation approaches.”

Unlike humans or mice, brittle stars present unique obstacles to research because they are considered “non-model organisms,” according to Jacob Machado, meaning they are studied much less than mice or humans and do not have the same protocols. Nonetheless, the anatomy of brittle stars provided the team with creative angles for points of comparison to establish control tissue regions versus those with expected regenerative properties in juxtaligamentous cells.

These JLCs were essential to the team’s investigation. In the paper, the research team explains the work to “quantify gene expression in the central region of the inner arm (enriched in JLC) of the brittle star Ophiomastix wendtii relative to the entire arm (containing the level basal (i.e. neither enriched nor depleted)) of the JLC) and the stomach (which is devoid of JLC).” This particular approach allowed the team to isolate a scale of relationships between JLCs and regenerative MCT production in regions of greater intensity, such as in the inner arm compared to the whole arm.

Since brittle star genomics does not have the same range of experimental protocols as mice and other species, the research team described important avenues for future exploration using ISH and RNAi to identify and target genes that control MCT. Jacob Machado hopes this gene targeting will serve as a catalyst for a prototype to drive future transformative human biomedical applications.

One of the most promising avenues is the development of what Jacob Machado describes as a “new dynamic and intelligent biomaterial,” based on a patent-pending collagen matrix developed from the interaction of JLC and MCT functionalities.

Jacob Machado considers this material to be a “collagen matrix that can change from flexibility to become as soft or stiff as we want.” The usefulness of this biomaterial in the medical field could be limitless, as it could serve as the basis for a rapid-response surgical glue for military personnel or function as “gelatinous origami” – to borrow Jacob Machado’s expression – for the place of traditional stents and others. measures to remedy blockages.

“Confirming the role of the identified candidate genes in controlling MCT tensile strength will open a wide range of new possibilities for both fundamental biology and biomedicine,” the research team wrote in the paper.

Future studies, the team says, will shed more light on the “evolution and molecular mechanisms of echinoderm MCT.” This deeper understanding could be the catalyst for future research advances by informing “the design of novel collagen-based biomaterials with dynamic and tunable mechanical properties for tissue engineering and regenerative medicine.”