Exploring metabolic noise opens new paths to better biomanufacturing

WashU researchers track single cells to reveal enzyme copy number fluctuation as the main source of metabolic noise.
Image Credits: Alex Schmitz and Xinyue Mu

Scientific Frontline: "At a Glance" Summary

• Main Discovery: Identification of enzyme copy number fluctuation arising from stochastic gene expression as the primary source of metabolic noise in microbial biomanufacturing.
• Methodology: Researchers utilized microfluidic devices to track single Escherichia coli cells engineered to produce betaxanthin (a yellow pigment), measuring both the metabolite and the enzyme concurrently during growth and division, followed by computational modeling and fermentation validation.
• Key Data: Approximately 50% of the observed metabolic noise stems from fluctuations in the production enzyme, while variations in cell growth rate account for less than 10% of the variability; cells were observed switching between high- and low-production states within a few hours.
• Significance: This finding clarifies why microbial productivity often fluctuates or drops in fermentation tanks, enabling the design of gene circuits that link higher enzyme expression to faster growth for sustained high-yield production.
• Future Application: Enhanced biomanufacturing of pharmaceuticals, supplements, biodegradable plastics, and fuels by deploying engineered strains that maintain peak metabolic activity.
• Branch of Science: Bioengineering, Synthetic Biology and Chemical Engineering.
• Additional Detail: This research supports the development of a zero-waste circular economy by improving the reliability of microbial fermentation processes.

Intraoperative Tumor Histology May Enable More-Effective Cancer Surgeries

From left to right: Images of kidney tissue as detected with UV-PAM, as imaged by AI to mimic traditional H&E staining, and as they appear when directly treated with H&E staining.
Image Credit: Courtesy of California Institute of Technology

Scientific Frontline: "At a Glance" Summary

• Main Discovery: Researchers developed ultraviolet photoacoustic microscopy (UV-PAM) integrated with deep learning to perform rapid, label-free, subcellular-resolution histology on excised tumor tissue directly in the operating room.
• Mechanism: A low-energy laser excites the absorption peaks of DNA and RNA nucleic acids to generate ultrasonic vibrations; AI algorithms then process these signals to create virtual images that mimic traditional hematoxylin and eosin (H&E) staining without chemical processing.
• Key Data: The system achieves a spatial resolution of 200 to 300 nanometers and delivers diagnostic results in under 10 minutes (potentially under 5 minutes), effectively identifying the dense, enlarged nuclei characteristic of cancer cells.
• Context: Unlike standard pathology, which requires time-consuming freezing, fixation, and slicing that can damage fatty tissues like breast tissue, this method preserves sample integrity and eliminates preparation artifacts.
• Significance: This technology aims to drastically reduce re-operation rates—currently up to one-third for breast cancer lumpectomies—by allowing surgeons to confirm clean tumor margins intraoperatively across various tissue types (breast, bone, skin, organ).

X-raying auditory ossicles – a new technique reveals structures in record time

Scientists at PSI were able to observe the local collagen structures in an ossicle by scanning it with an X-ray beam. The different colours of the cylinders indicate how strongly the collagen bundles are spatially aligned in a section measuring 20 by 20 by 20 micrometres.
Image Credit: © Paul Scherrer Institute PSI/Christian Appel

Scientific Frontline: "At a Glance" Summary

• Main Discovery: Researchers refined a "tensor tomography" X-ray diffraction technique that simultaneously detects biological structures ranging from nanometers to millimeters, significantly accelerating the imaging process.
• Methodology: The team used a precisely rotated X-ray beam (approx. 20 micrometers wide) to generate millions of interference patterns around two axes, which software then reconstructed into a 3D tomogram.
• Key Statistic: The optimized process reduced the measurement time for a complete tomogram from roughly 24 hours to just over one hour.
• Context: To validate the method, the team imaged the auditory ossicle (anvil) of the ear, successfully mapping the spatial orientation of nanometer-sized collagen fibers crucial for sound transmission.
• Significance: This drastic reduction in scan time makes statistical studies involving hundreds of samples feasible, aiding biomedical research in areas like bone tissue analysis and implant development.

What Is: Organoid

Organoids: The Science and Ethics of Mini-Organs
Image Credit: Scientific Frontline / AI generated

The "At a Glance" Summary

• Defining the Architecture: Unlike traditional cell cultures, organoids are 3D structures grown from pluripotent stem cells (iPSCs) or adult stem cells. They rely on the cells' intrinsic ability to self-organize, creating complex structures that mimic the lineage and spatial arrangement of an in vivo organ.
• The "Avatar" in the Lab: Organoids allow for Personalized Medicine. By growing an organoid from a specific patient's cells, researchers can test drug responses on a "digital twin" of that patient’s tumor or tissue, eliminating the guesswork of trial-and-error prescriptions.
• Bridge to Clinical Trials: Organoids serve as a critical bridge between the Petri dish and human clinical trials, potentially reducing the failure rate of new drugs and decreasing the reliance on animal testing models which often fail to predict human reactions.
• The Ethical Frontier: As cerebral organoids (mini-brains) become more complex, exhibiting brain waves similar to preterm infants, science faces a profound question: At what point does biological complexity become sentience?

Harnessing evolution: Evolved synthetic disordered proteins could address disease, antibiotic resistance

Yifan Dai and his team designed a method based on directed evolution to create synthetic intrinsically disordered proteins that can facilitate diverse phase behaviors in living cells. Intrinsically disordered proteins have different phase behaviors that take place at increasing or decreasing temperatures, as shown in the image above. The intrinsically disordered proteins on the left are cold responsive, and those on the right are hot responsive. The tree image in the center depicts the directed evolution process with the reversible intrinsically disordered proteins near the top. Feeding into the process from the bottom are soluble intrinsically disordered proteins.
Illustration Credit: Dai lab

The increased prevalence of antibiotic resistance could make common infections deadly again, which presents a threat to worldwide public health. Researchers in the McKelvey School of Engineering at Washington University in St. Louis have developed the first directed evolution-based method capable of evolving synthetic condensates and soluble disordered proteins that could eventually reverse antibiotic resistance.

Yifan Dai, assistant professor of biomedical engineering, and his team designed a method that is directed evolution-based to create synthetic intrinsically disordered proteins that can facilitate diverse phase behaviors in living cells. This allows them to build a toolbox of synthetic intrinsically disordered proteins with distinct phase behaviors and features that are responsive to temperatures in living cells, which helps them to create synthetic biomolecular condensates. In addition to reversing antibiotic resistance, the cells can regulate protein activity among cells. 

Stem cell engineering breakthrough paves way for next-generation living drugs

UBC research associate Dr. Ross Jones in the lab where they are working to develop cell-based therapies from stem cells.
Photo Credit: Phillip Chin.

For the first time, researchers at the University of British Columbia have demonstrated how to reliably produce an important type of human immune cell—known as helper T cells—from stem cells in a controlled laboratory setting.  

The findings, published today in Cell Stem Cell, overcome a major hurdle that has limited the development, affordability and large-scale manufacturing of cell therapies. The discovery could pave the way for more accessible and effective off-the-shelf treatments for a wide range of conditions like cancer, infectious diseases, autoimmune disorders and more.   

“Engineered cell therapies are transforming modern medicine,” said co-senior author Dr. Peter Zandstra, professor and director of the UBC School of Biomedical Engineering. “This study addresses one of the biggest challenges in making these lifesaving treatments accessible to more people, showing for the first time a reliable and scalable way to grow multiple immune cell types.”  

Pills that communicate from the stomach could improve medication adherence

Two photos show the gelatin-coated capsules (left) and the capsule without the coating (right). The capsule can be broken down and absorbed by the body.
Photo Credit: Courtesy of the researchers
(CC BY-NC-ND 4.0)

In an advance that could help ensure people are taking their medication on schedule, MIT engineers have designed a pill that can report when it has been swallowed.

The new reporting system, which can be incorporated into existing pill capsules, contains a biodegradable radio frequency antenna. After it sends out the signal that the pill has been consumed, most components break down in the stomach while a tiny RF chip passes out of the body through the digestive tract.

This type of system could be useful for monitoring transplant patients who need to take immunosuppressive drugs, or people with infections such as HIV or TB, who need treatment for an extended period of time, the researchers say.

Clean biogas – measurable everywhere

Ayush Agarwal worked on the analysis of biogas during his doctoral studies at the PSI Center for Energy and Environmental Sciences at PSI.
Photo Credit: © Paul Scherrer Institute PSI/Markus Fischer

Researchers at the Paul Scherrer Institute PSI have developed a new analytical method that can detect even tiny amounts of critical impurities in biogas. This procedure can be used even by small biogas plants without the need for major investment – thus facilitating the energy transition.

The market for biogas is growing. According to the Swiss Federal Office of Energy, Switzerland fed 471 gigawatt hours of this fuel into the natural gas grid last year – roughly twice the amount fed in ten years ago. This comes with an increase in the need to measure impurities in the biogas quickly and reliably, because strict quality criteria apply to this green gas.  

Researchers at PSI’s Center for Energy and Environmental Sciences have now come up with a solution to this problem. The analytical method they have developed can simultaneously detect the two most critical impurities in biogas: sulfur compounds and siloxanes. They have now presented their method in the journal Progress in Energy. 

Nasal drops fight brain tumors noninvasively

Researchers at WashU Medicine have developed a noninvasive medicine delivered through the nose that successfully eliminated deadly brain tumors in mice. The medicine is based on a spherical nucleic acid, a nanomaterial (labeled red) that travels along a nerve (green) from the nose to the brain, where it triggers an immune response to eliminate the tumor.
Image Credit: Courtesy of Alexander Stegh

Researchers at Washington University School of Medicine in St. Louis, along with collaborators at Northwestern University, have developed a noninvasive approach to treat one of the most aggressive and deadly brain cancers. Their technology uses precisely engineered structures assembled from nano-size materials to deliver potent tumor-fighting medicine to the brain through nasal drops. The novel delivery method is less invasive than similar treatments in development and was shown in mice to effectively treat glioblastoma by boosting the brain’s immune response.

Glioblastoma tumors form from brain cells called astrocytes and are the most common kind of brain cancer, affecting roughly three in 100,000 people in the U.S. Glioblastoma generally progresses very quickly and is almost always fatal. There are no curative treatments for the disease, in part because delivering medicines to the brain remains extremely challenging.

Focused Ultrasound Passes First Test in Treatment of Brain Cancer in Children

Pediatric oncologist Stergios Zacharoulis and biomedical engineer Elisa Konofagou are pioneering the use of focused ultrasound to treat brain cancer in children and dozens of other brain diseases
Photo Credit: Rudy Diaz / Columbia University Vagelos College of Physicians and Surgeons.

Columbia University researchers are the first to show that focused ultrasound—a non-invasive technique that uses sound waves to enhance the delivery of drugs into the brain—can be safely used in children being treated for brain cancer.

The focused ultrasound technique, developed by Columbia engineers, was tested in combination with chemotherapy in three children with diffuse midline glioma, a rare and aggressive brain cancer that is universally fatal.

The study found that focused ultrasound successfully opened the blood-brain barrier in all three patients, allowing the chemotherapy drug to reach the tumors and leading to some improvement in patient mobility, though all three patients eventually died from their disease or complications of COVID.

Seeing infrared with organic electrodes

Organic electrodes
Electrophysiological recording of retinal activity on a precision setup using controlled red-light conditions that do not alter the retina’s response. The experiment captures how the retina reacts to infrared photovoltaic stimulation
Photo Credit: Technische Universität Wien

In some people, the light receptors on the retina are damaged, but the underlying nerve structure is still intact. In this case, a visual implant could potentially help in the future: Biocompatible, thin photovoltaic films register radiation, convert it into electrical signals, and use these to stimulate living nerve tissue. This has now been achieved for the first time in laboratory tests at TU Wien. 

Bioengineering: In-Depth Description

Bioengineering is an interdisciplinary field that applies engineering principles, design concepts, and quantitative methods to biological systems. It bridges the gap between engineering and the life sciences to create solutions for problems in biology, medicine, agriculture, and environmental science. Its primary goals are to analyze and understand complex biological systems and to develop new technologies, materials, and therapies to improve human health, quality of life, and sustainability.

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.

Nonsurgical treatment shows promise for targeted seizure control

Jerzy Szablowski
Photo Credit: Jeff Fitlow/Rice University

Rice University bioengineers have demonstrated a nonsurgical way to quiet a seizure-relevant brain circuit in an animal model. The team used low-intensity focused ultrasound to briefly open the blood-brain barrier (BBB) in the hippocampus, delivered an engineered gene therapy only to that region and later flipped an on-demand “dimmer switch” with an oral drug. The research shows that a one-time, targeted procedure can modulate a specific brain region without impacting off-target areas of the brain.

“Many neurological diseases are driven by hyperactive cells at a particular location in the brain,” said study lead Jerzy Szablowski, assistant professor of bioengineering and a member of the Rice Neuroengineering Initiative. “Our approach aims the therapy where it is needed and lets you control it when you need it, without surgery and without a permanent implant.”

Nanorobots transform stem cells into bone cells

Prof. Berna Özkale Edelmann, together with researchers at her Microrobotic Bioengineering Lab at the Technical University of Munich (TUM), developed a system in which stem cells can be transformed into bone cells through mechanical stimulation.
Photo Credit: Astrid Eckert / Technische Universität München

For the first time, researchers at the Technical University of Munich (TUM) have succeeded in using nanorobots to stimulate stem cells with such precision that they are reliably transformed into bone cells. To achieve this, the robots exert external pressure on specific points in the cell wall. The new method offers opportunities for faster treatments in the future.

Prof. Berna Özkale Edelmann’s nanorobots consist of tiny gold rods and plastic chains. Several million of them are contained in a gel cushion measuring just 60 micrometers, together with a few human stem cells. Powered and controlled by laser light, the robots, which look like tiny balls, mechanically stimulate the cells by exerting pressure. “We heat the gel locally and use our system to precisely determine the forces with which the nanorobots press on the cell – thereby stimulating it,” explains the professor of nano- and microrobotics at TUM. This mechanical stimulation triggers biochemical processes in the cell. Ion channels change their properties, and proteins are activated, including one that is particularly important for bone formation.

SwRI-developed bioreactor replicates versatile induced Pluripotent Stem Cells

Southwest Research Institute demonstrated its single-use 3D bioreactor to produce induced Pluripotent Stem Cells (iPSCs), derived from adult skin, blood, and other somatic cells. Useful for personalized medicine, iPSCs offer an alternative to embryonic stem cells by differentiating into any other cell type in the body.
Photo Credit: Southwest Research Institute

Southwest Research Institute (SwRI) has demonstrated a new application for its cell-expansion bioreactor to advance tissue engineering and cell-based therapies for treatment of injuries and diseases. 

SwRI scientists used the bioreactor to replicate induced Pluripotent Stem Cells (iPSCs) derived from adult skin, blood, and other somatic cells. Their pluripotent state allows iPSCs to differentiate into any other cell type in the body, much like embryonic stem cells but without the same ethical ambiguity. Large quantities of iPSCs are needed for regenerative medicine and individualized healthcare, but current technology requires manual production. 

Prime time for fiber optics to take a deep dive into brain circuits

Fiber-optic technology is being refined for brain research. WashU engineers have developed a way to vastly expand the utility of a single fiber-optic line that can fit in the brain.
Image Credit: JJ Ying

Fiber-optic technology revolutionized the telecommunications industry and may soon do the same for brain research.

A group of researchers from Washington University in St. Louis in both the McKelvey School of Engineering and the School of Medicine have created a new kind of fiber-optic device to manipulate neural activity deep in the brain. The device, called PRIME (Panoramically Reconfigurable IlluMinativE) fiber, delivers multi-site, reconfigurable optical stimulation through a single, hair-thin implant.

“By combining fiber-based techniques with optogenetics, we can achieve deep-brain stimulation at unprecedented scale,” said Song Hu, professor of biomedical engineering, who collaborated with the laboratory of Adam Kepecs, professor of neuroscience and psychiatry at WashU Medicine. 

Controlling prostheses with the power of thought

 A neuroprosthesis. Artificial hands, arms, or legs can restore mobility to people with disabilities. The study investigated how the brain learns to control such prostheses via brain-computer interfaces.
Image Credit: © Sebastian Lehmann

Researchers at the German Primate Center (DPZ) – Leibniz Institute for Primate Research in Göttingen have discovered that the brain reorganizes itself extensively across several brain regions when it learns to perform movements in a virtual environment with the help of a brain-computer interface. The scientists were thus able to show how the brain adapts when controlling motor prostheses. The findings not only help to advance the development of brain-computer interfaces, but also improve our understanding of the fundamental neural processes underlying motor learning.

In order to perform precise movements, our brain's motor system must continuously recalibrate itself. If we want to shoot a basketball, this works well with a familiar basketball, but requires extra practice with a lighter or heavier ball. Our brain uses the deviations from the expected (throw) result as an error signal to learn better commands for the next throw. The brain must also perform this task when it wants to control a movement via a brain-computer interface (BCI), for example, that of a neuroprosthesis. Until now, it was unclear which regions of the brain reflect the expected result of the movement (the trajectory of the ball), which reflect the error signal, and which reflect the corrected movement command that aims to compensate for the previous error.

In a surprising discovery, scientists find tiny loops in the genomes of dividing cells

MIT experiments have revealed the existence of “microcompartments,” shown in yellow, within the 3D structure of the genome. These compartments are formed by tiny loops that may play a role in gene regulation.
Illustration Credit: Ed Banigan, edited by MIT News
(CC BY-NC-ND 4.0)

Before cells can divide, they first need to replicate all of their chromosomes, so that each of the daughter cells can receive a full set of genetic material. Until now, scientists had believed that as division occurs, the genome loses the distinctive 3D internal structure that it typically forms.

Once division is complete, it was thought, the genome gradually regains that complex, globular structure, which plays an essential role in controlling which genes are turned on in a given cell.

However, a new study from MIT shows that in fact, this picture is not fully accurate. Using a higher-resolution genome mapping technique, the research team discovered that small 3D loops connecting regulatory elements and genes persist in the genome during cell division, or mitosis.

“This study really helps to clarify how we should think about mitosis. In the past, mitosis was thought of as a blank slate, with no transcription and no structure related to gene activity. And we now know that that’s not quite the case,” says Anders Sejr Hansen, an associate professor of biological engineering at MIT. “What we see is that there’s always structure. It never goes away.”

Researchers use nanotubes to improve blood flow in bioengineered tissues

Assistant Professors Ying Wang (Department of Biomedical Engineering) and Yingge Zhou (School of Systems Science and Industrial Engineering) collaborated on research about engineered tissues.
Photo Credit: Jonathan Cohen.

When biomedical researchers need to test their latest ideas, they often turn to engineered human tissue that mimics the responses in our own bodies. It’s become an important intermediary step before human clinical trials.

One limiting factor: The cells need blood circulation to survive, and achieving that can be difficult in three-dimensional cell structures. Without proper vascular systems — even primitive ones — engineered tissue faces restricted size and functionality, even developing necrotic regions of dead cells.

New research from Binghamton University’s Thomas J. Watson College of Engineering and Applied Science offers a possible solution to the problem. In a paper recently published in the journal Biomedical Materials, Assistant Professors Ying Wang and Yingge Zhou show how the latest nanomanufacturing techniques can create a better artificial vascular system.