Showing posts sorted by date for query CRISPR. Sort by relevance Show all posts
Showing posts sorted by date for query CRISPR. Sort by relevance Show all posts

Friday, December 05, 2025

 

Engineering the next superfood: BTI unlocks goldenberry’s commercial potential





Boyce Thompson Institute
Erecta lines show compact growth habit 

image: 

"Erecta" goldenberry lines (right) show compact growth habit compared to the non-edited lines (left)

view more 

Credit: Van Eck Lab, Boyce Thompson Institute




Goldenberries taste like a cross between pineapple and mango, pack the nutritional punch of a superfood, and are increasingly popular in U.S. grocery stores. But the plants that produce these bright yellow-orange fruits grow wild and unruly—reaching heights that make large-scale farming impractical.

Researchers at the Boyce Thompson Institute (BTI) helped solve that problem. Using CRISPR gene editing, a collaborative team including BTI professor Joyce Van Eck engineered compact goldenberry plants that are 35% shorter than their wild relatives, making them viable for commercial agriculture.

"Goldenberry has tremendous potential as a nutritious crop, but its large, bushy growth habit has hindered commercial production," said Van Eck. "These new compact plants can be grown at higher density, don't require extensive staking or trellising, and are much easier to maintain and harvest."

The research, published in Plants, People, Planet, demonstrates how plant science-based solutions can rapidly improve minor crops that haven't benefited from traditional breeding programs.

From wild to farmable

Native to the Andean region of South America, goldenberry (Physalis peruviana) has been consumed for centuries but has undergone little domestication. Colombia currently produces more than 20,000 tons annually, with 40% exported to meet growing global demand.

The team leveraged knowledge from related Solanaceae crops, targeting the ERECTA gene that regulates stem length in tomatoes and groundcherries. Because goldenberry is tetraploid—containing four sets of chromosomes—the researchers needed to edit two separate copies of ERECTA.

Using CRISPR technology and transformation methods developed at BTI, they successfully generated plants with precise edits in both gene copies. After crossing the edited plants to select for preferred fruit flavor, the team produced stable "Erecta" lines that have 50% shorter internodes than wild-type plants.

The compact plants produce fruits averaging 3.3 grams, which are only slightly smaller than commercially available goldenberries sold in U.S. markets.

The team has already secured USDA clearance, confirming that the edited plants are free from plant pest regulations. Now, they'll be seeking FDA approval so growers can proceed with commercial production immediately.

Beyond goldenberries

A handful of crops—wheat, rice, corn, soybeans—dominate global food production, creating a fragile system vulnerable to disruption and disease. Meanwhile, hundreds of nutritious "minor crops" remain underutilized, often trapped between wild origins and commercial viability.

“This work demonstrates how gene editing can complement traditional plant breeding for minor crops," Van Eck said. "We can integrate decades of breeding knowledge from major crop species, use CRISPR to make precise changes to specific traits, and accelerate the development of improved varieties—adding a powerful new tool to plant breeders' toolkit.”

The team has identified several promising next steps for advancing goldenberry cultivation, including increasing fruit size, eliminating sticky acylsugars on fruit surfaces, and enabling synchronized ripening for efficient harvest. And the approach extends beyond goldenberries—similar strategies could improve passion fruit, groundcherry, and other underutilized crops with strong nutritional profiles and regional importance.

"Improving nutritious minor crops like goldenberry expands dietary diversity and creates new opportunities for farmers," added Van Eck. "That's exactly the kind of plant science-based solution BTI exists to deliver."

The research was supported by the National Science Foundation Plant Genome Research Program and involved collaboration with Cold Spring Harbor Laboratory and Johns Hopkins University.

About the Boyce Thompson Institute (BTI)
As an independent nonprofit research institute affiliated with Cornell University, our scientists are committed to advancing solutions for global food security, agricultural sustainability, and human health. Through groundbreaking research, transformative education, and rapid translation of discoveries into real-world applications, BTI bridges fundamental plant and molecular science with practical impact. Discovery inspired by plants. Learn more at BTIscience.org.

Wednesday, December 03, 2025

 

Sperm tails and male infertility: Critical protein revealed by ultrastructure microscope


RIKEN
Spermatogenesis viewed with ultrastructure expansion microscopy 

image: 

Ultrastructure expansion microscopy of murine male germ cells reveals the fine molecular structures of centrioles (shown in the enlarged image). DNA is stained in blue, and the chromosome axis in red.

view more 

Credit: RIKEN




Male infertility is a major issue worldwide and its causes remain unclear. Now, an international team of researchers led by Hiroki Shibuya at the RIKEN Center for Biosystems Dynamics Research (BDR) in Japan has discovered a key structure in the germ cells of male mice that, when disturbed, leads to deformations in sperm flagellum—the tail that allows sperm to swim. Made possible by the first observation of the mouse flagellar base structure using ultrastructure expansion microscopy, this finding could explain some forms of infertility in human men. The study was published in the scientific journal Science Advances.

When conception fails, it is often due to abnormalities in egg or sperm cells that occur during their development. In males, this process is called spermatogenesis and continues throughout life after puberty. Although we know a little bit about this process, scientists have yet to map everything that happens at the subcellular level.

“While the causes of female infertility have been studied extensively,” says Shibuya, “the mechanisms underlying male infertility—which are known to account for about half of all infertility cases—remain poorly understood.”

Shibuya and his team tackled this problem using a relatively new technology called ultrastructure expansion microscopy. Detailed images of the insides of cells can already be taken with an electron microscope. But you cannot identify specific proteins or track how a structure changes over time. On the other hand, fluorescent microscopy can’t normally visualize ultrastructures inside a cell. With ultrastructure expansion microscopy, the cells of interest are placed on a gel. The gel is then expanded many times its original size. Now standard immunofluorescence labeling combined with a fluorescent microscope can be used to look at the giant specimen and specific ultrastructures can be imaged with high resolution.

The researchers adapted this relatively new technology for male mouse germ cells by gently fixing and drying the cells onto coverslips before putting them in the gel. This prevented the cells from moving around, which is a problem for male germ cells. They also applied a treatment to remove excess cytoplasm, which improved the resolution.

Having solved these issues, Shibuya and his team focused their efforts on the centriole, a tiny cylindrical structure—only 450 nanometers in length and 200 nanometers in diameter—that undergoes major changes during spermatogenesis that allow the flagellum to form. A correctly formed flagellum is critical because without it, sperm cannot move properly and will never even reach an egg cell, let alone fertilize it. Using their modified protocol, the researchers were able to visualize both the proximal and distal centriole throughout the entire transformation from germ cell to sperm.

They found that the inner scaffold within the distal centriole becomes stronger after the completion of meiosis, when germ cells divide and the new cells contain only one copy of each gene. Fluorescent labeling of key proteins that make up the distal centriole inner scaffold showed an increase in centrin-POC5 protein complexes. How important are these proteins for fertility? A complete knockout of POC5 using CRISPR gene editing produced normal male mice with zero viable sperm. Detailed analysis revealed that while centriole function in regular cells was unaffected, the lack of POC5 caused malformed flagella that disintegrated, explaining why the mice were completely infertile.

“Our modified expansion microscopy protocol can be extended to other analyses, including human sperm, opening new possibilities for investigating fine structural abnormalities that account for male infertility,” says Shibuya. “In the long-term, this could lead to novel diagnostic and therapeutic approaches in reproductive medicine.”

Monday, December 01, 2025

 

VIRE: a global data platform to better understand viruses



Researchers release a comprehensive viral genome database covering diverse ecosystems to advance understanding of viral evolution and ecosystem functions





European Molecular Biology Laboratory





Researchers have developed VIRE, a database that integrates approximately 1.7 million viral genomes derived from more than 100,000 metagenomes worldwide. Metagenomic data is obtained by comprehensively sequencing all DNA present in an environment. This approach enables the recovery of genomic information from microorganisms and viruses that cannot be cultured in the laboratory.

The research was led by Peer Bork, Senior Scientist and Interim Director General at EMBL Heidelberg, and Suguru Nishijima, Project Associate Professor at the Life Science Data Research Center, Graduate School of Frontier Sciences, The University of Tokyo, and former Postdoctoral Fellow in the Bork Group. 

Viral Integrated Resource across Ecosystems (VIRE) is the largest and most comprehensive viral resource to date, providing a global foundation for understanding viral diversity across human-associated and environmental ecosystems. This work is expected to greatly advance understanding of the ecological roles of viruses and their interactions with microbial communities.

Although diverse viruses are known to inhabit ecosystems across the planet, the lack of a comprehensive framework has hindered systematic understanding of their global diversity. In particular, many viruses found in environments such as oceans, soils, and the human gut are bacteriophages, which infect bacteria. Because the majority of bacteriophages cannot be easily cultured in the laboratory, their diversity and functions have long remained elusive. 

Using state-of-the-art viral detection technologies, the team comprehensively identified viruses, primarily bacteriophages, across diverse environments such as the human body, oceans, and soils, and predicted their taxonomy, hosts, and gene functions. They also applied advanced computational approaches to detect viral genomes with high accuracy. This enabled them to collect and integrate approximately 1.7 million medium- to high-quality viral genomes, representing a vast expansion beyond existing viral databases.   

Furthermore, for viruses infecting bacteria and archaea, the team utilised the host defense mechanism known as CRISPR spacer sequences to infer host organisms with high precision. These are DNA sequences retained by bacteria and archaea as a record of past viral infections, and by analysing these sequences, it is possible to infer which viruses have previously infected which host organisms. The researchers also clarified the functions of viral genes by integrating annotations from multiple biological databases, such as KEGG and COG, which describe molecular pathways and gene functions.

VIRE is now the world’s largest integrated platform providing viral taxonomy, predicted hosts, and gene functions in a unified framework. It is expected to enable data-driven research across a wide range of fields, including viral ecology, microbial evolution, and environmental sciences. This achievement represents a major step forward in understanding the global diversity of viruses and will contribute to uncovering virus–microbe interactions as well as advancing studies on environmental change, human health, and disease.

Explore VIRE
 

 

 

Wednesday, November 26, 2025

 

The future of type 1 diabetes: Can stem cells provide a cure?



Xia & He Publishing Inc.





Type 1 diabetes (T1D) is an autoimmune disorder characterized by the specific destruction of insulin-producing pancreatic β-cells. While islet transplantation has demonstrated promise, its widespread application is hampered by immune rejection, the necessity for lifelong immunosuppression, and a critical shortage of donor organs. This review posits that regenerative medicine, particularly strategies centered on stem cells and pancreatic progenitor cells, holds the key to a lasting cure. We explore innovative avenues for regenerating functional β-cells, with a focused analysis on the potential of pancreatic progenitor cells, the conversion of resilient α-cells, and the reprogramming of senescent β-cells. Despite persistent challenges such as immune attack and suboptimal cell differentiation, harnessing endogenous regenerative mechanisms and engineering immune-evasive cells present a transformative pathway toward restoring physiological insulin production and liberating patients from exogenous insulin dependence.

Introduction
The pathogenesis of T1D involves a selective autoimmune attack on pancreatic β-cells, sparing other endocrine cells like glucagon-producing α-cells. This selectivity underscores a fundamental opportunity: leveraging the innate resistance of non-β cells for therapeutic regeneration. Current treatments, including islet transplantation, are plagued by the recurrence of autoimmunity and organ donor scarcity. This review critically synthesizes past research to hypothesize that the future of T1D management lies in activating the body's own regenerative potential or creating an inexhaustible source of immune-tolerant β-cells from stem cells.

The Search for Elusive Pancreatic Stem Cells
A central quest in the field is the identification of endogenous pancreatic stem or progenitor cells in adults. While a dedicated stem cell niche akin to the bone marrow is absent in the mature pancreas, evidence points to the ductal epithelium as a reservoir of cells with progenitor-like capabilities. Advances in single-cell transcriptomics are now empowering researchers to identify and characterize these rare, transient cell populations, mapping their potential to differentiate into endocrine lineages. Concurrently, the derivation of β-like cells from pluripotent stem cells (e.g., embryonic or induced pluripotent stem cells) has progressed to clinical trials (e.g., ViaCyte, Vertex Pharmaceuticals), showing restored insulin production in patients. The dual approach—activating endogenous progenitors and transplanting externally differentiated cells—represents a powerful, scalable strategy.

Replicating β-cells and the Potential of Ductal Epithelium
Historically, β-cell mass expansion was thought to occur primarily through the replication of existing β-cells. However, this process is limited and often accompanied by temporary dedifferentiation, compromising function. In contrast, the process of neogenesis—the formation of new islets from progenitor cells—offers a more robust solution. The ductal epithelium exhibits remarkable plasticity, capable of generating new β-cells, especially in response to injury, metabolic stress, or specific signaling cues. Key pathways like Notch and Wnt, along with the inhibition of the Hippo pathway (activating YAP), have been shown to enhance this ductal-to-β-cell conversion, highlighting a viable therapeutic target for regeneration.

Unlocking Secrets from α-Cell Resilience
A pivotal insight for T1D therapy is the inherent resistance of α-cells to autoimmune destruction. This resilience is multi-faceted: α-cells express lower levels of key autoantigens, possess stronger anti-apoptotic signaling, exhibit greater endurance against inflammatory cytokines like interferon-gamma, and may reside in a more protected microenvironment within the islet. This inherent "immune privilege" provides a blueprint for protecting β-cells. Strategies such as molecular mimicry (engineering β-cells to express α-cell protective molecules), immune checkpoint modulation (e.g., introducing PD-1), and anti-inflammatory cytokine therapy (e.g., IL-10) are being explored to shield β-cells from immune attack.

Key Signaling Pathways in β-Cell Regeneration
Reversing T1D requires a deep understanding of the molecular pathways governing β-cell development and identity.

  • NGN3 (Neurogenin 3): A master regulator of endocrine differentiation, NGN3 reactivation in adult ductal or acinar cells can drive the formation of new, glucose-responsive β-like cells.

  • Wnt/β-catenin and Hippo/YAP: These pathways are crucial for progenitor cell proliferation, survival, and differentiation. Their targeted activation promotes the expansion and maturation of β-cell precursors.

  • GLP-1 (Glucagon-like peptide-1): Beyond its insulinotropic effects, GLP-1 enhances β-cell survival, proliferation, and even promotes the transdifferentiation of α-cells into β-like cells.

  • GDF11 (Growth differentiation factor 11): This factor shows promise in stimulating β-cell regeneration and may counteract age-related decline in regenerative capacity.

Bench-to-Bedside Strategies and Technical Hurdles
The translational pipeline is rich with diverse approaches, including stem cell-derived β-cells, autologous iPSC therapies, drug-induced endogenous regeneration (e.g., glucagon receptor antagonists), cellular reprogramming, and encapsulation technologies. However, significant hurdles remain. These include the functional immaturity of stem cell-derived β-cells, the risk of immune rejection even with matched cells, challenges in scaling up production under Good Manufacturing Practice, and the risk of tumorigenicity from residual pluripotent cells. Encapsulation devices face issues with fibrosis and limited nutrient diffusion, while gene-editing strategies like CRISPR, though promising for creating immune-evasive cells, raise concerns about off-target effects.

Future Directions and Conclusion
The future of T1D cure lies in integrated, systems-level approaches. This includes employing biomimetic scaffolds and organ-on-chip systems to improve β-cell maturation, using multi-omics to precisely map cell fates, and combining regenerative therapies with antigen-specific immunomodulation to create a tolerant microenvironment. Furthermore, research must address the neuroendocrine integration of regenerated β-cells and leverage artificial intelligence for personalized treatment strategies.

In conclusion, while challenges in scalability, safety, and immune compatibility are substantial, the convergence of stem cell biology, regenerative signaling, and immunoengineering is paving a concrete path toward a cure for T1D. The vision is shifting from lifelong insulin management to the restoration of endogenous, functional β-cell mass, offering the genuine prospect of insulin independence for patients.

 

Full text:

https://www.xiahepublishing.com/2472-0712/ERHM-2024-00002

 

The study was recently published in the Exploratory Research and Hypothesis in Medicine.

Exploratory Research and Hypothesis in Medicine (ERHM) publishes original exploratory research articles and state-of-the-art reviews that focus on novel findings and the most recent scientific advances that support new hypotheses in medicine. The journal accepts a wide range of topics, including innovative diagnostic and therapeutic modalities as well as insightful theories related to the practice of medicine. The exploratory research published in ERHM does not necessarily need to be comprehensive and conclusive, but the study design must be solid, the methodologies must be reliable, the results must be true, and the hypothesis must be rational and justifiable with evidence.