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Category: bioengineering

How to build a genome: Scientists release troubleshooting manual for synthetic life

Leading synthetic biologists have shared hard-won lessons from their decade-long quest to build the world’s first synthetic eukaryotic genome in a Nature Biotechnology paper. Their insights could accelerate development of the next generation of engineered organisms, from climate-resilient crops to custom-built cell factories.

“We’ve assembled a comprehensive overview of the literature on how to build a lifeform where we review what went right—but also what went wrong,” says Dr. Paige Erpf, lead author of the paper and postdoctoral researcher at Macquarie University’s School of Natural Sciences and the Australian Research Council (ARC) Center of Excellence in Synthetic Biology.

The Synthetic Yeast Genome Project (Sc2.0) involved a large, evolving global consortium of 200-plus researchers from more than ten institutions, who jointly set out to redesign and chemically synthesize all 16 chromosomes of baker’s yeast from scratch. Macquarie University contributed to the synthesis of two of these chromosomes, comprising around 12% of the project overall.

Molecular basis for de novo thymus regeneration in a vertebrate, the axolotl

In humans, the loss of thymic function through thymectomy, environmental challenges, or age-dependent involution is associated with increased mortality, inflammaging, and higher risk of cancer and autoimmune disease (1). This is largely due to a decline in the intrathymic naïve T cell pool, whose generation is orchestrated by the thymic stroma, particularly thymic epithelial cells (TECs) (2). Upon challenges that affect the TEC compartment, the thymus is capable of triggering an endogenous regenerative response by engaging resident epithelial progenitors with stem cell features (3–5). Yet, after age-related atrophy or thymectomy resulting from myasthenia gravis or tumor removal (1), this regenerative response is unable to overcome the loss of thymic tissue, highlighting the need for therapeutic interventions.

The restoration of thymic functionality has been achieved to a limited extent via strategies targeting the thymic epithelial microenvironment or hematopoietic progenitors, modulating hormones and metabolism, or through cellular therapies and bioengineering (6). In mice, the up-regulation of Foxn1, a key transcription factor for thymus development and organogenesis (7), either directly or via its upstream effector bone morphogenetic protein 4 (BMP4), can support activity of cortical TECs (cTECs) (8, 9). Further, a combination of growth hormone and metformin has been shown to restore thymic functional mass in humans (10). Nevertheless, such strategies only lead to delayed thymic involution, and examples of complete thymus regeneration have not yet been described among vertebrates.

Because of its remarkable regenerative abilities that extend to parts of the brain, eye, heart, and spinal cord, and even entire limbs, the axolotl (Ambystoma mexicanum) is a powerful model for regeneration studies (11). The axolotl has offered insights into the mechanisms of positional identity (12), cell plasticity (13, 14), and the molecular basis of complex regeneration (15–18). The regeneration of axolotl body parts relies on remnants of the missing structure, with the exception of lens tissue, which can regrow from dorsal pigmented epithelial cells during a short window during development (19). However, whether de novo regeneration can occur for an entire complex organ, in axolotls or any other vertebrate, is unknown.

Unified EEG imaging improves mapping for epilepsy surgery

A new advance from Carnegie Mellon University researchers could reshape how clinicians identify the brain regions responsible for drug-resistant epilepsy. Surgery can be a life-changing option for millions of epilepsy patients worldwide, but only if physicians can accurately locate the epileptogenic zone, the area where seizures originate.

Bin He, professor of biomedical engineering, and his team have developed a unified, machine learning-based approach called spatial-temporal-spectral imaging (STSI) to assist. It is the first technology capable of analyzing every major type of epileptic brain signal within a single computational framework.

Their work, published in PNAS, presents a technical breakthrough and promising new direction for noninvasive presurgical planning.

Gene editing creates compact goldenberry plants suitable for large-scale farming

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.”

Extreme engineering: Unlocking design secrets of deep-sea microbes

The microbe Pyrodictium abyssi is an archaeon—a member of what’s known as the third domain of life—and an extremophile. It lives in deep-sea thermal vents, at temperatures above the boiling point of water, without light or oxygen, withstanding the enormous pressure at ocean depths of thousands of meters.

A biomatrix of tiny tubes of protein, known as cannulae, link cells of Pyrodictium abyssi together into a highly stable microbial community. No one knew how these single-celled microbes accomplished this feat of extreme engineering—until now.

A study using advanced microscopy techniques reveals new details about the elegant design of the cannulae and the remarkable simplicity of their method of construction. Nature Communications published the work, led by scientists at Emory University; the University of Virginia, Charlottesville; and Vrije Universiteit Brussel in Belgium.

Synthetic neuroscience grants promote transformative brain tech

The Wu Tsai Neurosciences Institute, Sarafan ChEM-H, and Stanford Bio-X have awarded $1.24 million in grants to five innovative, interdisciplinary, and collaborative research projects at the intersection of neuroscience and synthetic biology.

The emerging field of synthetic neuroscience aims to leverage the precision tools of synthetic biology — like gene editing, protein engineering, and the design of biological circuits — to manipulate and understand neural systems at unprecedented levels. By creating custom-made biological components and integrating them with neural networks, synthetic neuroscience offers new ways to explore brain function, develop novel therapies for neurological disorders, and even design biohybrid systems that could one day allow brains to interface seamlessly with technology.

“The ongoing revolution in synthetic biology is allowing us to create powerful new molecular tools for biological science and clinical translation,” said Kang Shen, Vincent V.C. Woo Director of the Wu Tsai Neurosciences Institute. “With these awards, we wanted to bring the Stanford neuroscience community together to capitalize on this pivotal moment, focusing the power of cutting-edge synthetic biology on advancing our understanding of the nervous system — and its potential to promote human health and wellbeing.”

Switching risk and protective alleles improves Alzheimer’s-disease-like signatures and disruptions in mice

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the progressive degradation of brain cells, as well as an associated decline in memory and other mental functions. Earlier research found that different forms (i.e., alleles) of a gene known as apolipoprotein E (APOE) are associated with an increased or decreased risk of developing AD.

The APOE gene can be mutated into different variants (i.e., alleles), including APOE2, APOE3 and APOE4. Past studies have linked the presence of two APOE4 alleles to a higher risk of developing AD, while two APOE2 alleles were linked to a significantly lower risk of AD.

Researchers at the University of Kentucky and other institutes genetically engineered a type of mouse that carries a genetic “switch” that can be activated with a drug and that converts the harmful APOE4 allele into the protective APOE2 allele.

Dynamic duo of bacteria could change Mars dust into versatile building material for first human colonists

Since humanity’s first steps on the moon, the aspiration to extend human civilization beyond Earth has been a central objective of international space agencies, targeting long-term extraterrestrial habitation. Among the celestial bodies within reach, Mars is considered our next home.

The red planet, with its stark landscapes and tantalizing similarities to Earth, beckons as the frontier of human exploration and settlement. But establishing a permanent foothold on Mars remains one of humanity’s boldest dreams and the most formidable scientific and engineering challenge.

The red planet, once draped in a thick atmosphere, has undergone dramatic transformation over billions of years. Its protective blanket vanished, leaving behind an environment nearly unrecognizable to terrestrial life.

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