Major findings on the inner workings of a brittle star’s ability to reversibly control the pliability of its tissues will help researchers solve the puzzle of mutable collagenous tissue (MCT) and potentially inspire new “smart” biomaterials for human health applications.
The work is directed by Denis Jacob Machado—assistant professor in Bioinformatics at The University of North Carolina at Charlotte Center for Computational Intelligence to Predict Health and Environmental Risks (CIPHER)—and Vladimir Mashanov, staff scientist at Wake Forest Institute for Regenerative Medicine.
In “Unveiling putative modulators of mutable collagenous tissue in the brittle star Ophiomastix wendtii: an RNA-Seq analysis,” published recently in BMC Genomics, the researchers describe using advanced transmission electron microscopy (TEM), RNA sequencing, and other bioinformatics methods to identify 16 potential MCT modulator genes. This research offers a breakthrough towards understanding precisely how echinoderms quickly and drastically transform their collagenous tissue. The first author of the paper, Reyhaneh Nouri, is a Ph.D. student in UNC Charlotte’s Department of Bioinformatics and Genomics.
“We’re uncovering the precise instructions that DNA sends to the cell—what it’s saying, when it’s saying it, and in what quantities. Think of DNA as the captain of a ship, issuing commands to navigate and operate smoothly. The RNA is the crew, diligently receiving those orders and carrying them out to ensure the ship’s mission is accomplished. We are looking into what the crew is doing and learning from their hard work,” Jacob Machado explained.
This advanced research to pinpoint relevant molecular processes in an echinoderm could eventually open new doors for regenerative therapies in humans.
Echinoderms, like brittle stars (a cousin of the seastars and sand dollars) and sea cucumbers, possess remarkable abilities to adapt their bodily tissues in response to stressors and rapidly changing conditions, including detaching significant portions of their body to escape predation or other dangerous situations. Some species of brittle stars are particularly suited to provide researchers with a viable test case for isolating MCT modulator genes, which are the specific molecular instructions determining emergent tissue modifications.
The new findings are intended to shape the future development of smart and dynamic collagen-based biomaterials to treat human health conditions, such as helping to heal wounds faster or providing alternative materials for tissue regeneration that do not trigger immune rejection.
Already, Jacob Machado and his colleagues at UNC Charlotte have a provisional patent pending on the building blocks of what would be considered a revolutionary collagen-based biomaterial, to be developed by industry. Still, there are several key stages of research ahead.
“It starts with you daring to look into something completely new without knowing if it’s going to work or not,” Jacob Machado said.
The published research examines a clear genomic relationship between brittle star juxtaligamental cells (JLCs) and reversible collagenous modulation, identifying 16 different genes that represent a big—and exciting—”question mark,” Jacob Machado said.
In upcoming research—using techniques like in situ hybridization (ISH) and RNA interference (RNAi) to “hunt down” these genes—Jacob Machado said the team can study “what happens to the echinoderms once some of those genes are turned off.”
This process of genomic detection and elimination will allow the team to determine whether the putative MCT genes “are involved in specific functionalities in mutable collagenous tissues,” according to Jacob Machado, who expects the next stage of research will be completed over the next year and a half.
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Pathway to novel collagen matrix and biomaterial
The research so far, Jacob Machado says, fuses 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 capable” team operating transition electron microscopes—forming an imaginative team approach to “experimental designs” for analyzing RNA.
Led by Jacob Machado and Mashanov, the research team from UNC Charlotte’s Department of Bioinformatics and Genomics includes Nouri, April Harris, Gari New, William Taylor (student and staff), Daniel Janies and Robert W. Reid (faculty).
While echinoderm collagenous tissue modulation is familiar to scientists, the average beachcomber, and hungry fish alike, the team’s research puts science on an accelerated path to understanding cellular tissue regeneration.
In BMC Genomics, the researchers write the “study is the first attempt at discovering novel genes specific to the echinoderm MCT using state-of-the-art sequencing, differential gene expression, and annotation approaches.”
Unlike humans or mice, brittle stars present unique barriers to research because they are considered “non-model organisms,” according to Jacob Machado, meaning that they are much less studied than mice or humans, and do not have the same protocols. Still, brittle star anatomy afforded the team creative angles for points of comparison to establish control tissue regions against those with anticipated regenerative properties in juxtaligamental cells.
These JLCs were vital to the team’s investigation. In the paper, the research team explains the work to “quantify gene expression in the inner arm core region (enriched in JLCs) of the brittle star Ophiomastix wendtii compared to the whole arm (containing the basal level (i.e., neither enriched nor depleted) of the JLCs) and stomach (which is devoid of JLCs).” This particular approach afforded the team a means to isolate a scale of relationships between JLCs and the regenerative production of MCTs within regions of greater intensity, such as in the inner arm versus the whole arm.
Since brittle star genomics lacks the same available range of experimental protocols as mice and other species, the research team has outlined significant pathways for future exploration using ISH and RNAi to identify and zero in on the genes that control MCT. Jacob Machado is hopeful this genetic targeting will be the 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 “smart dynamic new biomaterial,” based around a patent-pending collagen matrix developed from the interaction of JLC and MCT functionality.
Jacob Machado envisions this material as a “collagen matrix that can change its pliability to become as soft or rigid as we want.” The utility of this biomaterial in the medical field could be boundless, as it could serve as the basis for rapid-response surgical glue for military personnel or function as “gelatinous origami”—to use Jacob Machado’s phrase—in place of traditional stents and similar measures to address blockages.
“Confirming the role of the identified candidate genes in controlling MCT tensile strength will open up 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 further illuminate “the evolution and molecular mechanisms of the echinoderm MCT.” This deeper understanding could be the catalyst for future research breakthroughs by informing “the design of new collagen-based biomaterials with dynamic, tunable mechanical properties for tissue engineering and regenerative medicine.”
More information:
Reyhaneh Nouri et al, Unveiling putative modulators of mutable collagenous tissue in the brittle star Ophiomastix wendtii: an RNA-Seq analysis, BMC Genomics (2024). DOI: 10.1186/s12864-024-10926-7
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University of North Carolina at Charlotte
Citation:
Unlocking the secrets of collagen: How sea creature superpowers are inspiring smart biomaterials for human health (2024, December 6)
