Scientists rebuild microscopic circadian clock to control genes

Image Credit: Scientific Frontline

Scientific Frontline: "At a Glance" Summary

• Main Discovery: Researchers reproduced the simplest natural circadian system found in blue-green algae (cyanobacteria) within a test tube, demonstrating how a single clock signal coordinates daily gene switching.
• Methodology: The team utilized biochemical, structural, and in vivo methods to recreate the rhythmic genetic switching process in vitro, observing how the mechanism turns off "morning" genes while simultaneously activating "evening" genes.
• Key Data: The study successfully modeled the "antiphase" gene expression where cellular processes peak distinctly at dusk and dawn, orchestrated by a simplified clocking mechanism relative to complex organisms.
• Significance: This research elucidates the fundamental molecular mechanisms by which circadian clocks regulate gene activity, revealing how immense cellular complexity is managed by a simple rhythmic system.
• Future Application: Findings may enable the development of scheduling tools for the timed biosynthesis of valuable compounds in biotechnology and offer new strategies for regulating human gut microbiota to support overall health.
• Branch of Science: Molecular Biology, Chronobiology, and Biotechnology
• Additional Detail: The study, published in Nature Structural and Molecular Biology, highlights the potential connection between unstable circadian rhythms and mental health issues, as well as the optimization of medicine administration timing.

Engineered moths could replace mice in research into “one of the biggest threats to human health”

CRISPR/Cas9 technology in Galleria mellonella (greater wax moth) enables precise gene editing and the generation of transgenic lines, enhancing its use as an ethical, low-cost in vivo model for infection biology and antimicrobial resistance research
Image Credit: Courtesy of University of Exeter

Scientific Frontline: "At a Glance" Summary

• Main Discovery: Scientists at the University of Exeter have developed the world's first genetically engineered greater wax moths (Galleria mellonella) to serve as advanced alternatives to rodents in infection research.
• Methodology: The research team adapted genetic tools originally designed for fruit flies, utilizing PiggyBac mediated transgenesis and CRISPR/Cas9 knockout techniques to create fluorescent and gene-edited moth lines.
• Key Data: Replacing just 10% of UK infection biology studies with these engineered moths would spare approximately 10,000 mice annually from the estimated 100,000 currently utilized.
• Significance: This development addresses the critical bottleneck in antimicrobial resistance (AMR) testing by providing a scalable, ethical non-mammalian model that survives at human body temperature (37°C) and mimics mammalian immune responses.
• Future Application: The creation of "sensor moths" that fluoresce upon infection or antibiotic contact will allow for real-time, visual monitoring of disease processes and rapid drug screening.
• Branch of Science: Biotechnology and Infection Biology
• Additional Detail: All developed protocols and genetic resources have been made openly available through the Galleria Mellonella Research Center to accelerate global standardization and adoption.

New Line of Bovine Embryonic Stem Cells Shows Promise for Lab-Grown Meat, Biomedical Applications

Cindy Tian of the Department of Animal Science in the College of Agriculture, Health and Natural Resources works in her lab in the Agricultural Biotechnology Laboratory (ABL). Oct. 19, 2022.
Photo Credit: Milton Levin/UConn

Scientific Frontline: "At a Glance" Summary

• Main Discovery: Researchers have established a novel line of bovine embryonic stem cells (ESCs) derived from the blastocyst stage that maintain a stable, formative pluripotent state.
• Methodology: The cells were cultured using a specialized "cocktail" medium consisting of a commercial base supplemented with specific small molecules and mouse feeder cells to prevent natural differentiation.
• Key Data: This cell line is genetically "clean," containing zero foreign genes unlike induced pluripotent stem cells (iPSCs), and possesses the unique capacity to directly induce primordial germ cell-like cells.
• Significance: The absence of genetic engineering addresses critical safety and regulatory hurdles for cultivated meat production, offering a more efficient and consistent alternative to traditional reprogramming methods.
• Future Application: These cells are intended for the commercial scaling of lab-grown muscle and fat, the development of disease-resistant cattle, and the creation of large-animal models for human medical research.
• Branch of Science: Agricultural Science, Animal Science, and Biotechnology.
• Additional Detail: Ongoing research aims to eliminate the requirement for mouse feeder cells and develop a long-term maintenance medium to reduce environmental impact and production costs.

Not only toxic but also a nutrient: guanidine as a nitrogen source

Cyanobacteria convert light energy into chemical energy through photosynthesis and are becoming increasingly important for carbon-neutral biotechnology.
Photo Credit: André Künzelmann / UFZ

Scientific Frontline: "At a Glance" Summary

• Main Discovery: Cyanobacteria possess the capability to actively absorb and catabolize guanidine (CH5N3) as their sole nitrogen source, refuting the prior scientific consensus that the compound acts exclusively as a toxic denaturant in these organisms.
• Methodology: The study utilized an interdisciplinary approach combining genome analysis, molecular microbiology, biochemical binding assays, and simulation-based process analytics to map the complete metabolic pathway and regulatory networks.
• Specific Mechanism: Uptake is facilitated by a newly identified, high-affinity ATP-binding cassette (ABC) transport system effective at low concentrations, while intracellular guanidine hydrolase converts the substrate into ammonium and urea for metabolic integration.
• Key Regulation Detail: Gene expression for the transporter and hydrolase is controlled by a specific riboswitch that directly binds guanidine, functioning as a precise sensor to regulate uptake and trigger efflux systems if intracellular levels become toxic.
• Ecological Context: These findings suggest that free guanidine is naturally available and constitutes an overlooked but integral component of global biogeochemical nitrogen cycles, providing a colonization advantage for cyanobacteria.
• Future Application: The identified riboswitch mechanism offers a novel, cost-effective molecular tool for synthetic biology, enabling researchers to finely tune gene expression in cyanobacterial "green cell factories" by modulating guanidine levels.

Beyond gene scissors: New CRISPR mechanism discovered

Cryo-electron microscope structure of the nuclease Cas12a3 cleaving the tail of a transfer RNA (tRNA).
 Image Credit: Biao Yuan / Helmholtz Zentrum für Infektionsforschung HZI

The CRISPR “gene scissors” have become an important basis for genome-editing technologies in many fields, ranging from biology and medicine to agriculture and industry. A team from the Helmholtz Institute for RNA-based Infection Research (HIRI) in Würzburg has now demonstrated that these CRISPR-Cas systems are even more versatile than previously thought. 

In cooperation with the Helmholtz Centre for Infection Research (HZI) in Braunschweig and Utah State University (USU) in Logan (USA), the scientists have discovered a novel CRISPR defense mechanism: Unlike known nucleases, Cas12a3 specifically destroys transfer ribonucleic acids (tRNA) that are vital for protein production to shut down infected cells. The team published its findings today in the journal Nature. 

Bacteria contain a wide variety of mechanisms to fend off invaders like viruses. One of these strategies involves cleaving transferring ribonucleic acids (tRNA), which are present in all cells and play a fundamental role in the translation of messenger RNA (mRNA) into essential proteins. Their inactivation limits protein production, causing the infected cell to go dormant. As a result, the attacker cannot continue to replicate and spread within the bacterial population. 

Raising strong yeast as a petroleum substitute

Strengthened Saccharomyces cerevisiae   
This common yeast is a strong contender for replacing petroleum in 2,3-butanediol production.   
Image Credit: Osaka Metropolitan University

As fossil fuels rise in cost and green initiatives gain traction, alternative methods for producing useful compounds using microorganisms have the potential to become sustainable, environmentally friendly technologies.

One such process involves the common bread yeast, Saccharomyces cerevisiae (S. cerevisiae), to produce 2,3-butanediol (2,3-BDO), an organic compound often used in pharmaceuticals and cosmetics. However, this yeast has a low tolerance for 2,3-BDO under high concentrations, which leads to a decline in its production ability and hinders the mass commercialization of this method.

Jellyfish can be used to make mayonnaise and butter

Photo Credit: Marat Gilyadzinov

Researchers at the University of Southern Denmark (SDU) have discovered that jellyfish can be used as a food stabiliser. In the future, the slimy creatures may become an important ingredient in a more sustainable food production system.

Food stabiliser.

The word might not sound particularly appetizing, but without food stabilizers, much of the food we eat would be impossible to make. It would not be able to retain its consistency or form but would split or spread out. 

Nature itself has created many stabilizers to maintain the structure of organisms, and over time, we humans have learned to use them in our food. 

The most well-known example in the home kitchen is egg yolk, which allows mayonnaise to bind together. In the industrial food sector, stabilizers are even more crucial. Here, ingredients such as starch, pectin, gelatine, and algal stabilizers are used to achieve the right consistency in everything from ketchup to chocolate milk. 

Scientists use algae to convert food waste into sustainable ingredients

C-phycocyanin
Photo Credit: King Abdullah University of Science and Technology

Researchers at King Abdullah University of Science and Technology (KAUST) have discovered something new about a very old organism and used it to transform waste from a chocolate factory into C-phycocyanin, a valuable blue pigment that is estimated to have a global market value of over US$275 million by 2030.  

The study, published in Trends in Biotechnology, outlines how Galdieria yellowstonensis, an ancient strain of red algae, can eat the sugars found in chocolate-processing waste to grow into a protein-rich biomass containing C-phycocyanin, which is used in food, cosmetics, and pharmaceutical products. Adding to the findings was the unexpected discovery that high levels of carbon dioxide promote Galdieria growth. Normally, carbon dioxide is a waste produced by microbes eating sugar. 

Genetic Engineering: Changing the Number of Chromosomes in Plants Using Molecular Scissors

For the first time, KIT researchers managed to reduce the number of chromosomes in a plant by fusing two chromosomes.
Illustration Credit: Michelle Rönspies – KIT

Higher yields, greater resilience to climatic changes or diseases – the demands on crop plants are constantly growing. To address these challenges, researchers at Karlsruhe Institute of Technology (KIT) are developing new methods in genetic engineering. In cooperation with other German and Czech researchers, they succeeded for the first time in leveraging the CRISPR/Cas molecular scissors for changing the number of chromosomes in the Arabidopsis thaliana model organism in a targeted way – without any adverse effects on plant growth. This discovery opens up new perspectives for plant breeding and agriculture.  

A system for targeted drug delivery using magnetic microrobots

Microrobots can be transported and activated in a safe and controlled manner, marking a decisive step forward in the use of these technological devices in targeted medical treatments.
Photo Credit: Courtesy of University of Barcelona

The study, led by the Swiss Federal Institute of Technology Zurich (ETH Zurich) and published in the journal Science, involves Professor Josep Puigmartí-Luis from the Faculty of Chemistry and the Institute of Theoretical and Computational Chemistry (IQTC) of the University of Barcelona. He is the only researcher from a Spanish institution to sign this paper, which is the result of the European ANGIE project, an initiative coordinated by Professor Salvador Pané (ETH) in collaboration with the Chemistry In Flow and Nanomaterials Synthesis (ChemInFlow) research group, led by Professor Puigmartí. 

The new microrobotic platform presents an innovative strategy for administering drugs in a precise and targeted manner. It is scalable and can be applied to numerous situations in which the administration of therapeutic agents is difficult to access, such as tumors, arteriovenous malformations, localized infections, or tissue injuries. 

Biotechnology: In-Depth Description

Image Credit: Scientific Frontline / stock image

Biotechnology is the integration of natural sciences and engineering sciences to apply organisms, cells, parts thereof, and molecular analogues to products and services. Its primary goal is to leverage biological systems and processes to develop technologies and products that help solve problems, improve human health, enhance food production, and create more sustainable industrial and environmental processes.

New ultrasound technique could help aging and injured brains

Raag Airan, Matine Azadian, Payton Martinez, and Yun Xiang in the lab. Azadian is holding a version of their ultrasound apparatus designed for humans.
Photo Credit: Andrew Brodhead

Just like your body needs a bath now and then, so too does your brain – but instead of a tub filled with hot water, your brain has cerebrospinal fluid, which flows around inside the brain and helps clear away waste products, misplaced blood cells, and other sometimes-toxic debris.

The trouble is, that natural brain-bathing system can break down as people age or after a brain injury, such as a stroke – and there aren’t any particularly good ways to help the brain out in those situations. Indeed, current ideas to promote cerebrospinal fluid cleaning are either rather invasive or require drugs that may not be safe or effective in people.

Fortunately, a team of Stanford researchers has found a radically simple tool that may help the brain wash itself out without the need for drugs or invasive procedures: ultrasound, the same tool obstetricians regularly use at prenatal checkups.

Fermentation waste used to make natural fabric

 

Penn State Professor Melik Demirel, to the far right, his students and their families wear biomanufactured sweaters. Pictured are Khushank Singhal and Oguzhan Colak, both affiliated with the Department of Engineering Science and Mechanics in the College of Engineering; Ceren Colak, Ela Demirel and Emir Demirel.
Photo Credit: © Oguzhan Colak

A fermentation byproduct might help to solve two major global challenges: world hunger and the environmental impact of fast fashion. The leftover yeast from brewing beer, wine or even to make some pharmaceuticals can be repurposed to produce high-performance fibers stronger than natural fibers with significantly less environmental impact, according to a new study led by researchers at Penn State and published in the Proceedings of the National Academy of Sciences. 

The yeast biomass — composed of proteins, fatty molecules called lipids and sugars — left over from alcohol and pharmaceutical production is regarded as waste, but lead author Melik Demirel, Pearce Professor of Engineering and Huck Chair in Biomimetic Materials at Penn State, said his team realized they could repurpose the material to make fibers using a previously developed process. The researchers successfully achieved pilot-scale production of the fiber — producing more than 1,000pounds — in a factory in Germany, with continuous and batch production for more than 100 hours per run of fiber spinning.

They also used data collected during this production for a lifecycle assessment, which assessed the needs and impact of the product from obtaining the raw fermentation byproduct through its life to disposal and its cost, and to evaluate the economic viability of the technology. The analysis predicted the cost, water use, production output, greenhouse gas emissions and more at every stage. Ultimately, the researchers found that the commercial-scale production of the fermentation-based fiber could compete with wool and other fibers at scale but with considerably fewer resources, including far less land — even when accounting for the land needed to grow the crops used in the fermentation processes that eventually produce the yeast biomass.   

Birch leaves and peanuts turned into advanced laser technology

Upper: The biomaterial-based random laser when activated. Lower: The same laser seen in daylight.
 Photo Credit: Zhihao Huang

Physicists at Umeå University, in collaboration with researchers in China, have developed a laser made entirely from biomaterials – birch leaves and peanut kernels. The environmentally friendly laser could become an inexpensive and accessible tool for medical diagnostics and imaging.

The results have been published in the scientific journal Nanophotonics and show how a so-called random laser can be made entirely from biological materials.

“Our study shows that it is possible to create advanced optical technology in a simple way using only local, renewable materials,” says Jia Wang, Associate Professor at the Department of Physics, Umeå University, and one of the authors of the study.

A random laser is a type of laser in which light scatters many times inside a disordered material before emerging as a focused beam. It holds great promise for applications such as medical imaging and early disease detection, and has therefore attracted significant research attention. However, conventional random laser materials are often toxic or expensive and complex to produce.

Scientists Produce Powerhouse Pigment Behind Octopus Camouflage

An octopus camouflages itself with the seafloor. UC San Diego scientists have discovered a new way to produce large amounts of xanthommatin, a natural pigment used in animal camouflage, in a bacterium for the first time.
Photo Credit: Charlotte Seid

Scientists at UC San Diego have moved one step closer to unlocking a superpower held by some of nature’s greatest “masters of disguise.”

Octopuses, squids, cuttlefish and other animals in the cephalopod family are well known for their ability to camouflage, changing the color of their skin to blend in with the environment. This remarkable display of mimicry is made possible by complex biological processes involving xanthommatin, a natural pigment.

Because of its color-shifting capabilities, xanthommatin has long intrigued scientists and even the military, but has proven difficult to produce and research in the lab — until now.

UrFU Scientists Have Identified New Beneficial Properties of Mushrooms

According to the biologist, the production of lanolin ointment with extracts of tinder mushrooms does not require high costs.
Photo Credit: UrFU press service

UrFU biologists have identified the beneficial properties of tinder mushrooms. They found that an ointment based on lanolin and extracts from tinder helps heal wounds faster after burns, even third-degree burns that form scars. The ointment also reduces inflammation. The results of tests on rats were published in Bulletin of Siberian Medicine scientific journal.

“In order for the wound to heal, it is necessary not only to repair the cells but also the intercellular substance – the skin framework. This long process occurs in several stages. If this process is delayed, negative consequences may occur, such as severe inflammation or scarring. Lanolin-based ointments with tinder mushroom extracts promote the formation of new cells and reduce inflammation, which in turn accelerates the healing process,” said Alexander Ermoshin, Head of the Laboratory of Molecular and Cellular Biotechnology.

Scientists develop an efficient method of producing proteins from E. coli

Proteins are synthesized through two processes involving DNA: transcription, which converts DNA into mRNA; and translation, where ribosomes read the mRNA and sequentially link amino acids to form proteins. This image illustrates the translation process accelerated to produce proteins more efficiently.
 Image Credit: Teruyo Ojima-Kato

Proteins sourced from microorganisms are attracting attention for their potential in biomanufacturing a variety of products, including pharmaceuticals, industrial enzymes, and diagnostic antibodies. These proteins can also be used for converting resources into biofuels and bioplastics, which could serve as viable alternatives to petroleum-based fuels and products. Therefore, efficiently producing microbial proteins could make a significant contribution to sustainable manufacturing.

Producing proteins from Escherichia coli (E. coli) has become popular due to its cost-effectiveness and efficiency. However, yields of protein production in E. coli may be reduced depending on the specific gene sequence of the target protein.

A new system can dial expression of synthetic genes up or down

MIT engineers developed a way to set gene expression levels at off, low, or high. Using skin cells, the researchers delivered a cocktail (labeled with a red fluorescent protein, top row) that boosts the conversion of skin cells into motor neurons. Via promoter editing, they show that higher levels of this cocktail increase the number of motor neurons (green). In the bottom row, the same cells are labeled with a green fluorescent protein that is generated after the cells convert to motor neurons.
Image Credit: Courtesy of the researchers
(CC BY-NC-ND 4.0)

For decades, synthetic biologists have been developing gene circuits that can be transferred into cells for applications such as reprogramming a stem cell into a neuron or generating a protein that could help treat a disease such as fragile X syndrome.

These gene circuits are typically delivered into cells by carriers such as nonpathogenic viruses. However, it has been difficult to ensure that these cells end up producing the correct amount of the protein encoded by the synthetic gene.

To overcome that obstacle, MIT engineers have designed a new control mechanism that allows them to establish a desired protein level, or set point, for any gene circuit. This approach also allows them to edit the set point after the circuit is delivered.

“This is a really stable and multifunctional tool. The tool is very modular, so there are a lot of transgenes you could control with this system,” says Katie Galloway, an assistant professor in Chemical Engineering at MIT and the senior author of the new study.

New technique detects genetic mutations in brain tumors during surgery within just 25 minutes

During neurosurgery at Nagoya University Hospital
Photo Credit: Department of Neurosurgery, Graduate School of Medicine, Nagoya University

A research team in Japan has developed an innovative system that can accurately detect genetic mutations in the brain tumor within just 25 minutes. Genetic mutations are crucial markers for diagnosis of brain tumors.

Unlike conventional genetic analysis methods, which typically take one to two days to obtain results, this new system allows surgeons to identify genotyping of brain tumors and determine optimal resection margins during surgery.

The new system succeeded in detecting mutations in isocitrate dehydrogenase (IDH) and telomerase reverse transcriptase (TERT) promoters. These mutations are key markers for diagnosis of diffuse glioma—the most common type of brain tumor—which exhibit highly infiltrative nature. The findings were published in the journal Neuro-Oncology.

Stem Cell Technique Could Preserve Endangered Bird Species

Avian stem cells in culture (blue, left) that be efficiently converted in large numbers into germ cells (green, right).
Image Credit: C. Lois

Birds are a critical part of the global ecosystem; they enable our food production through consumption of agricultural pests like aphids and rodents, and control the spread of diseases by eating insects like mosquitos and ticks. However, around 15 percent of all bird species now face risk of extinction—in Hawaii alone, 33 of the state's 45 native species are critically endangered.

Caltech researchers have now developed technology to freeze and preserve stem cells from birds that can then be reconstituted to help propagate populations.

The work was conducted by Caltech postdoctoral scholar Xi Chen as a collaboration between the USC laboratory of Qi-Long Ying and the Caltech laboratory of Carlos Lois, research professor of biology. The study is described in a paper in the journal Nature Biotechnology.