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Biotechnology and Bioengineering

Unlocking the Secrets of Aging: Scientists Discover the Switch that Controls Cellular Renewal

Scientists have discovered that starving and then refeeding worms can reveal surprising secrets about aging. When a specific gene (called TFEB) is missing, these worms don’t bounce back from fasting—they instead enter a state that looks a lot like aging in humans, with signs of stress and cell damage. This research gives scientists a simple but powerful way to study how aging begins—and how it might be stopped. Even more intriguing, the same process might help explain how some cancer cells survive treatment by going into a kind of sleep mode.

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As humans age, our cells undergo a process called senescence, where they become dysfunctional and can no longer divide. This leads to a range of age-related diseases and physical decline. Scientists have been studying this phenomenon in the hopes of finding new ways to promote cellular renewal and prevent or reverse aging. Recently, researchers made a groundbreaking discovery that sheds light on the mechanisms behind cellular senescence.

Using Caenorhabditis elegans (C. elegans), also known as nematode worms, scientists manipulated a specific gene called TFEB, which regulates cellular responses to nutrient availability. When these worms were subjected to long-term fasting followed by refeeding, they typically regenerated and appeared rejuvenated under normal conditions. However, when the researchers removed TFEB from the equation, the worm’s stem cells failed to recover from the fasting period and instead entered a senescent-like state.

This senescent-like state was characterized by various markers, including DNA damage, nucleolus expansion, mitochondrial reactive oxygen species (ROS), and the expression of inflammatory markers – all similar to those observed in mammalian senescence. This finding provided scientists with a new model for studying senescence at the organismal level.

According to Adam Antebi, head of the study and director at the Max Planck Institute for Biology of Ageing, “We present a model for studying senescence at the level of the entire organism. It provides a tool to explore how senescence can be triggered and overcome.”

The researchers discovered that TFEB plays a crucial role in responding to fasting by regulating gene expression. Without it, worms attempt to initiate growth programs without sufficient nutrients, leading to senescence. They also identified growth factors like insulin and transforming growth factor beta (TGFbeta) as key signaling molecules dysregulated upon TFEB loss.

This new understanding of the TFEB-TGFbeta signaling axis has implications for finding treatments targeting senescent cells during aging as well as cancer dormancy. The researchers aim to test their worm model in the future to find new treatments targeting these areas.

In summary, this groundbreaking study sheds light on the mechanisms behind cellular senescence and provides a powerful tool for exploring how senescence can be triggered and overcome.

Behavioral Science

“Rewired for Romance: Scientists Give Gift-Giving Behavior to Singing Fruit Flies”

By flipping a single genetic switch, researchers made one fruit fly species adopt the gift-giving courtship of another, showing how tiny brain rewiring can drive evolutionary change.

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Rewired for Romance: Scientists Give Gift-Giving Behavior to Singing Fruit Flies

In a groundbreaking study published in the journal Science, researchers from Japan have successfully transferred a unique courtship behavior from one species of fruit fly to another. By activating a single gene in insulin-producing neurons, the team made Drosophila melanogaster, a species that typically sings “courtship songs,” perform a gift-giving ritual it had never done before.

The study reveals that the reason for this difference lies in the connection between insulin-producing neurons and the courtship control center in the brain. In gift-giving flies (D. subobscura), these cells are connected, while in singing flies (D. melanogaster), they remain disconnected. This discovery highlights that the evolution of novel behaviors does not necessarily require the emergence of new neurons; instead, small-scale genetic rewiring can lead to behavioral diversification and species differentiation.

The researchers inserted DNA into D. subobscura embryos to create flies with heat-activated proteins in specific brain cells. They used heat to activate groups of these cells and compared the brains of flies that did and did not regurgitate food. The study identified 16-18 insulin-producing neurons that make the male-specific protein FruM, clustered in a part of the brain called the pars intercerebralis.

“Our findings indicate that the evolution of novel behaviors does not necessarily require the emergence of new neurons; instead, small-scale genetic rewiring in a few preexisting neurons can lead to behavioral diversification and, ultimately, contribute to species differentiation,” said Dr. Yusuke Hara, co-lead author from the National Institute of Information and Communications Technology (NICT).

This study demonstrates how scientists can trace complex behaviors like nuptial gift-giving back to their genetic roots to understand how evolution creates entirely new strategies that help species survive and reproduce.

The research was conducted with support from KAKENHI Grant-in-Aid for Scientific Research and has been published in the journal Science on August 14, 2025.

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Biotechnology and Bioengineering

A Trojan Horse Approach: Bacteria-Delivered Viruses Show Promise in Cancer Treatment

Scientists have engineered a groundbreaking cancer treatment that uses bacteria to smuggle viruses directly into tumors, bypassing the immune system and delivering a powerful one-two punch against cancer cells. The bacteria act like Trojan horses, carrying viral payloads to cancer’s core, where the virus can spread and destroy malignant cells. Built-in safety features ensure the virus can’t multiply outside the tumor, offering a promising pathway for safe, targeted therapy.

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Researchers at Columbia Engineering have made a groundbreaking discovery that combines bacteria and viruses to create an innovative cancer treatment approach. In a recent study published in Nature Biomedical Engineering, the Synthetic Biological Systems Lab presents a system called CAPPSID (Coordinated Activity of Prokaryote and Picornavirus for Safe Intracellular Delivery). This technology leverages the tumor-seeking abilities of Salmonella typhimurium bacteria to deliver viruses directly into cancerous cells.

The approach bridges bacterial engineering with synthetic virology, allowing the bacteria to act as a Trojan horse by ferrying the virus past the body’s immune system and releasing it inside the tumor. The researchers believe that this technology represents the first example of engineered cooperation between bacteria and cancer-targeting viruses.

One of the biggest hurdles in oncolytic virus therapy is the body’s defense system, which can neutralize the virus before it reaches a tumor. The Columbia team sidestepped this problem by hiding the virus inside the tumor-seeking bacterium, making it invisible to circulating antibodies.

The CAPPSID system combines the bacteria’s instinct for homing in on tumors with the virus’s knack for infecting and killing cancer cells. By exploiting these characteristics, the researchers created a delivery system that can penetrate the tumor and spread throughout it, overcoming the limitations of both bacteria- and virus-only approaches.

A key concern with any live virus therapy is controlling its spread beyond the tumor. The team’s system solved this problem by making sure the virus couldn’t spread without a molecule it can only get from the bacteria. Since the bacteria stay put in the tumor, this vital component isn’t available anywhere else in the body.

The researchers believe that this technology has significant potential for future clinical applications and are currently testing the approach in a wider range of cancers using different tumor types, mouse models, viruses, and payloads. They are also evaluating how this system can be combined with strains of bacteria that have already demonstrated safety in clinical trials.

As a physician-scientist, Jonathan Pabón’s goal is to bring living medicines into the clinic, and efforts toward clinical translation are currently underway to translate the technology out of the lab. The team has filed a patent application related to this work and is looking ahead to developing a “toolkit” of viral therapies that can sense and respond to specific conditions inside a cell.

This publication marks a significant step toward making bacteria-virus systems available for future clinical applications, and it is systems like these – specifically oriented towards enhancing the safety of living therapies – that will be essential for translating advances into the clinic.

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Artificial Intelligence

Accelerating Evolution: The Power of T7-ORACLE in Protein Engineering

Researchers at Scripps have created T7-ORACLE, a powerful new tool that speeds up evolution, allowing scientists to design and improve proteins thousands of times faster than nature. Using engineered bacteria and a modified viral replication system, this method can create new protein versions in days instead of months. In tests, it quickly produced enzymes that could survive extreme doses of antibiotics, showing how it could help develop better medicines, cancer treatments, and other breakthroughs far more quickly than ever before.

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The accelerated evolution engine known as T7-ORACLE has revolutionized the field of medicine and biotechnology by allowing researchers to evolve proteins with new or improved functions at an unprecedented rate. This breakthrough was achieved by Scripps Research scientists who have developed a synthetic biology platform that enables continuous evolution inside cells without damaging the cell’s genome.

Directed evolution is a laboratory process where mutations are introduced, and variants with improved function are selected over multiple cycles. Traditional methods require labor-intensive steps and can take weeks or more to complete. In contrast, T7-ORACLE accelerates this process by enabling simultaneous mutation and selection with each round of cell division, making it possible to evolve proteins continuously and precisely inside cells.

T7-ORACLE circumvents the bottlenecks associated with traditional approaches by engineering E. coli bacteria to host a second, artificial DNA replication system derived from bacteriophage T7. This allows for continuous hypermutation and accelerated evolution of biomacromolecules, making it possible to evolve proteins in days instead of months.

To demonstrate the power of T7-ORACLE, researchers inserted a common antibiotic resistance gene into the system and exposed E. coli cells to escalating doses of various antibiotics. In less than a week, the system evolved versions of the enzyme that could resist antibiotic levels up to 5,000 times higher than the original.

The broader potential of T7-ORACLE lies in its adaptability as a platform for protein engineering. Scientists can insert genes from humans, viruses, or other sources into plasmids and introduce them into E. coli cells, which are then mutated by T7-ORACLE to generate variant proteins that can be screened or selected for improved function.

This could help scientists more rapidly evolve antibodies to target specific cancers, evolve more effective therapeutic enzymes, and design proteases that target proteins involved in cancer and neurodegenerative disease. The system’s ease of implementation, combined with its scalability, makes it a valuable tool for advancing synthetic biology.

The research team is currently focused on evolving human-derived enzymes for therapeutic use and tailoring proteases to recognize specific cancer-related protein sequences. In the future, they aim to explore the possibility of evolving polymerases that can replicate entirely unnatural nucleic acids, opening up possibilities in synthetic genomics.

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