New hope for MS

Micah Feri (left) and Seema Tiwari-Woodruff.
Photo Credit: Courtesy of University of California, Riverside

Multiple sclerosis, or MS, is a chronic autoimmune disease affecting more than 2.9 million people worldwide. It occurs when the immune system mistakenly attacks the myelin sheath, the protective insulation around nerve fibers, causing disruption of nerve signals between the brain and body. Symptoms can include numbness, tingling, vision loss, and paralysis.

While current treatments can reduce inflammation, no therapies yet exist to protect neurons or restore the damaged myelin sheath. Researchers have now taken a major step forward in the development of such a therapy, supported by funding from the National Multiple Sclerosis Society. They have identified two compounds that could remyelinate damaged axons.

Published in the journal Scientific Reports, the research, led by Seema Tiwari-Woodruff, a professor of biomedical sciences at the University of California, Riverside, School of Medicine, and John Katzenellenbogen, a professor of chemistry at the University of Illinois Urbana-Champaign, or UIUC, was made possible through two National MS Society funding programs: a traditional investigator-initiated grant and the Society’s Fast Forward commercial accelerator program.

Converting toxic styrene oxide into attractive compounds

Selvapravin Kumaran, doctoral student in the Microbial Biotechnology working group, takes a measurement in the laboratory. 
Photo Credit: © Dirk Tischler

Styrene oxide isomerase is proving to be a multifunctional helper for biotechnology.

The bacterial membrane enzyme styrene oxide isomerase can convert toxic compounds into valuable materials. Selvapravin Kumaran, a doctoral student in Professor Dirk Tischler's Microbial Biotechnology working group at Ruhr University Bochum, Germany, has discovered exactly how it does this. These findings could help in the future to use the multifunctional enzyme in other reactions involving the production of industrially attractive compounds from inexpensive precursors. “Enzymes are a powerful tool that can make our lives more environmentally friendly,” says Dirk Tischler. The researchers report their findings in the journal ACS Catalysis.

An enzyme with a previously unexplored mechanism

Bacterial styrene oxidase isomerase has been known to science for over three decades, but its mechanism of action has not yet been elucidated. “Working with this enzyme is difficult because it is anchored in the membrane of the bacterial cell system,” says Dirk Tischler. In collaboration with Delft University of Technology, his team was able to uncover the role of the amino acid tyrosine in the conversion of toxic styrene oxide through the rare Meinwald rearrangement.

Brain inflammation treatment could be ally in fight against dementia

Samira Aghlara-Fotovat
Photo Credit: Jeff Fitlow/Rice University

Scientists from Rice University and Houston Methodist have developed a new way to reduce inflammation in the brain, a discovery that could help fight diseases such as Alzheimer’s and Parkinson’s.

The team created “AstroCapsules,” small hydrogel capsules that enclose human astrocytes ⎯ star-shaped brain cells that support healthy nervous system function. Inside the capsules, the cells were engineered to release interleukin-1 receptor antagonist, an anti-inflammatory protein. Tests in human brain organoids and mouse models showed the treatment lowered neuroinflammation and resisted immune rejection.

Rice bioengineer Omid Veiseh, whose lab studies how to design biomaterials that work with the immune system, is co-corresponding author on the paper published in Biomaterials.

“Encapsulating cells in a way that shields them from immune attack has been a central challenge in the field,” said Veiseh, professor of bioengineering at Rice, Cancer Prevention and Research Institute of Texas Scholar and director of the Rice Biotech Launch Pad. “In our lab, we have been working on biomaterials for many years, and this project was an opportunity to draw from that experience to address the uniquely complex immune environment of the brain. Our hope is that this work will help move cell therapies closer to becoming real treatment options for patients with neurodegenerative disease.”

Supercharging vinegar’s wound healing power

Image Credit: Courtesy of Flinders University

A new study suggests adding microscopic particles to vinegar can make them more effective against dangerous bacterial infections, with hopes the combination could help combat antibiotic resistance.

The research, led by researchers at QIMR Berghofer, Flinders University and the University of Bergen in Norway, has resulted in the ability to boost the natural bacterial killing qualities of vinegar by adding antimicrobial nanoparticles made from carbon and cobalt.

Wounds that do not heal are often caused by bacterial infections and are particularly dangerous for the elderly and people with diabetes, cancer and other conditions.

Acetic acid (more commonly known as vinegar) has been used for centuries as a disinfectant, but it is only effective against a small number of bacteria, and it does not kill the most dangerous types.

The findings have been published in the international journal ACS Nano.

Possible breakthrough in the development of effective biomaterials

Professor Dr. Shikha Dhiman from the Department of Chemistry of JGU
Photo Credit: © Ankit Sakhuja

When model cell membranes bind to biomaterials, it is not the binding strength but the speed of the receptors in the membranes that is crucial

Many hopes rested on so-called tissue engineering: With the help of stem cells, skin and other organs could be grown, thereby enabling better wound healing and better transplants. Although some of this is already a reality, the level expected around 20 years ago has not yet been achieved because the stem cells do not always bind to the required host material as they should in theory. An international research team led by chemist Professor Shikha Dhiman from Johannes Gutenberg University Mainz (JGU) has now found the reason for this: "Whether an interaction between model cell membrane and matrix material occurs depends not only on the strength of the interaction but also on the speed at which the binding partner molecules move. The understanding of this interaction that we have now gained is crucial for the development of effective biomaterials," says Dhiman. The team's results were recently published in the renowned scientific journal PNAS.

Improved Brain Decoder Holds Promise for Communication in People with Aphasia

Brain activity like this, measured in an fMRI machine, can be used to train a brain decoder to decipher what a person is thinking about. In this latest study, UT Austin researchers have developed a method to adapt their brain decoder to new users far faster than the original training, even when the user has difficulty comprehending language.
Image Credit: Jerry Tang/University of Texas at Austin.

People with aphasia — a brain disorder affecting about a million people in the U.S. — struggle to turn their thoughts into words and comprehend spoken language.

A pair of researchers at The University of Texas at Austin has demonstrated an AI-based tool that can translate a person’s thoughts into continuous text, without requiring the person to comprehend spoken words. And the process of training the tool on a person’s own unique patterns of brain activity takes only about an hour. This builds on the team’s earlier work creating a brain decoder that required many hours of training on a person’s brain activity as the person listened to audio stories. This latest advance suggests it may be possible, with further refinement, for brain computer interfaces to improve communication in people with aphasia.

“Being able to access semantic representations using both language and vision opens new doors for neurotechnology, especially for people who struggle to produce and comprehend language,” said Jerry Tang, a postdoctoral researcher at UT in the lab of Alex Huth and first author on a paper describing the work in Current Biology. “It gives us a way to create language-based brain computer interfaces without requiring any amount of language comprehension.”

Self-Assembling Cerebral Blood Vessels: A Breakthrough in Alzheimer’s Treatment

Image Credit: Courtesy of Pohang University of Science and Technology

A 3D model accurately mimicking the Blood-Brain Barrier (BBB) in a laboratory environment has been successfully developed by research teams led by Professor Jinah Jang from the Departments of Mechanical Engineering, Life Sciences, IT Convergence Engineering, and the Graduate School of Convergence at POSTECH, and Professor Sun Ha Paek from the Department of Neurosurgery at Seoul National University Hospital. This study was recently published in Biomaterials Research, an international academic journal on materials science.

Neurodegenerative diseases, including Alzheimer’s, Parkinson’s disease, and amyotrophic lateral sclerosis (ALS), result from the progressive decline of brain and nervous system functions, primarily due to aging. Chronic neuroinflammation, a key driver of these disorders, arises from the intricate interactions between cerebral blood vessels and neural cells, where the BBB plays a pivotal regulatory role. However, existing BBB models have been unable to replicate the complex three-dimensional 3D structure of cerebral blood vessels, posing significant challenges for research and drug development.

Plant-based substitute for fossil fuels developed for plastic foams

Ziqi Yu (Postdoc), Isaac Nartey Oduro (PhD student) and Daniela Gonzalez- Sepulveda (undergraduate RA) are examining lignin-based polyurethane samples.
Photo Credit: Courtesy of Washington State University

An environmentally-friendly preparation of plant material from pine could serve as a substitute for petroleum-based chemicals in polyurethane foams.

The innovation could lead to more environmentally friendly versions of foams used ubiquitously in products such as kitchen sponges, foam cushions, coatings, adhesives, packaging and insulation. The global market for polyurethane totaled more than $75 billion in 2022.

A Washington State University-led research team used an environmentally-friendly preparation of lignin as a substitute for 20% of the fossil fuel-based chemicals in the foam. The bio-based foam was as strong and flexible as typical polyurethane foam. They report on their work in the journal, ACS Sustainable Chemistry and Engineering.

 “It’s quite novel in terms of the material we generate and the process we have,” said Xiao Zhang, corresponding author on the paper and professor in the Gene and Linda Voiland School of Chemical Engineering and Bioengineering. “Our extracted lignin offers a new class of renewable building blocks for the development of bio-based value-added products.”

Tracking delivery: new technology for nanocarriers

Lipid nanoparticles visualized using SCP-Nano technology at the cellular level in lung tissue.
Image Credit: © Ali Ertürk / Helmholtz Munich

How can we ensure that life-saving drugs or genetic therapies reach their intended target cells without causing harmful side effects? Researchers at Helmholtz Munich, LMU and Technical University Munich (TUM) have taken an important step to answer this question. They have developed a method that, for the first time, enables the precise detection of nanocarriers – tiny transport vehicles – throughout the entire mouse body at a single-cell level. This innovation, called “Single-Cell Profiling of Nanocarriers” or short “SCP-Nano”, combines advanced imaging with artificial intelligence to provide unparalleled insights into the functionality of nanotechnology-based therapies. The results, published in Nature Biotechnology, pave the way for safer and more effective treatments, including mRNA vaccines and gene therapies.

Nanocarriers will play a central role in the next wave of life-saving medicines. They enable the targeted delivery of drugs, genes, or proteins to cells within patients. With SCP-Nano, researchers can analyze the distribution of extremely low doses of nanocarriers throughout the entire mouse body, visualizing each cell that has taken them up. SCP-Nano combines optical tissue clearing, light-sheet microscopy imaging, and deep-learning algorithms. First, whole mouse bodies are made transparent. After the three-dimensional imaging of whole mouse bodies, nanocarriers within the transparent tissues can then be identified down to the single-cell level. By integrating AI-based analysis, researchers can quantify which cells and tissues are interacting with the nanocarriers and precisely where this occurs.

Scientists engineer CRISPR enzymes that evade the immune system

Image Credit: Natalie Velez, Broad Communications

The core components of CRISPR-based genome-editing therapies are bacterial proteins called nucleases that can stimulate unwanted immune responses in people, increasing the chances of side effects and making these therapies potentially less effective. 

Researchers at the Broad Institute of MIT and Harvard and Cyrus Biotechnology have now engineered two CRISPR nucleases, Cas9 and Cas12, to mask them from the immune system. The team identified protein sequences on each nuclease that trigger the immune system and used computational modeling to design new versions that evade immune recognition. The engineered enzymes had similar gene-editing efficiency and reduced immune responses compared to standard nucleases in mice.

Appearing today in Nature Communications, the findings could help pave the way for safer, more efficient gene therapies. The study was led by Feng Zhang, a core institute member at the Broad and an Investigator at the McGovern Institute for Brain Research at MIT.

“As CRISPR therapies enter the clinic, there is a growing need to ensure that these tools are as safe as possible, and this work tackles one aspect of that challenge,” said Zhang, who is also a co-director of the K. Lisa Yang and Hock E. Tan Center for Molecular Therapeutics, the James and Patricia Poitras Professor of Neuroscience, and a professor at MIT. He is an Investigator at the Howard Hughes Medical Institute.

Scientists identify Achilles heel of lung cancer protein

Researchers have shown for the first time that a crucial interface in a protein that drives cancer growth could act as a target for more effective treatments.

The study, led by the Science and Technology Facilities Council (STFC) Central Laser Facility (CLF) with support from the Imaging Therapies and Cancer Group at King's, used advanced laser imaging techniques to identify structural details of a mutated protein which help it to evade drugs that target it.

The study was published in the journal Nature Communications and lays the groundwork for future research into more effective, long-lasting cancer therapies.

The Epidermal Growth Factor Receptor (EGFR) is a protein that sits on the surface of cells and receives molecular signals that tell the cell to grow and divide. In certain types of cancer, mutated EGFR stimulate uncontrolled growth, resulting in tumors.

Various cancer treatments block and inhibit mutant EGFR to prevent tumor formation, but these are limited as eventually cancerous cells commonly develop further EGFR mutations that are resistant to treatment.

Until now, how exactly these drug-resistant EGFR mutations drive tumor growth was not understood, hindering our ability to develop treatments that target them.

Purdue researchers create biocompatible nanoparticles to enhance systemic delivery of cancer immunotherapy

Purdue University researchers are developing and validating patent-pending nanoparticles (left) to enhance immunotherapy effects against tumors. The nanoparticles are modified with adenosine triphosphate, or ATP, to recruit dendritic cells (right), which are immune cells that recognize tumor antigens and bring specialized immune cells to fight off tumors.
Image Credit: Yoon Yeo

Purdue University researchers are developing and validating patent-pending poly (lactic-co-glycolic acid), or PLGA, nanoparticles modified with adenosine triphosphate, or ATP, to enhance immunotherapy effects against malignant tumors.

The nanoparticles slowly release drugs that induce immunogenic cell death, or ICD, in tumors. ICD generates tumor antigens and other molecules to bring immune cells to a tumor’s microenvironment. The researchers have attached ATP to the nanoparticles, which also recruits immune cells to the tumor to initiate anti-tumor immune responses. 

Yoon Yeo leads a team of researchers from the College of Pharmacy, the Metabolite Profiling Facility in the Bindley Bioscience Center, and the Purdue Institute for Cancer Research to develop the nanoparticles. Yeo is the associate department head and Lillian Barboul Thomas Professor of Industrial and Molecular Pharmaceutics and Biomedical Engineering; she is also a member of the Purdue Institute for Drug Discovery and the Purdue Institute for Cancer Research.

The researchers validated their work using paclitaxel, a chemotherapy drug used to treat several types of cancers. They found that tumors grew slower in mice treated with paclitaxel enclosed within ATP-modified nanoparticles than in mice treated with paclitaxel in non-modified nanoparticles.

“When combined with an existing immunotherapy drug, the ATP-modified, paclitaxel-loaded nanoparticles eliminated tumors in mice and protected them from rechallenge with tumor cells,” Yeo said.

Rice study identifies protein responsible for gas vesicle clustering in bacteria

Zongru Li (left) and George Lu
Photo Credit: Anna Stafford/Rice University

Gas vesicles are hollow structures made of protein found in the cells of certain microorganisms, and researchers at Rice University believe they can be programmed for use in biomedical applications.

“Inside cells, gas vesicles are packed in a beautiful honeycomb pattern. How this pattern is formed has never been thoroughly understood. We are presenting the first identification of a protein that can regulate this patterning, and we believe this will be a milestone in molecular microbiology,” said George Lu, assistant professor of bioengineering and a Cancer Prevention and Research Institute of Texas scholar.

Lu and colleagues have published their findings in a paper published in Nature Microbiology. The lead author is Zongru Li, a fourth-year bioengineering doctoral student in Lu’s Laboratory for Synthetic Macromolecular Assemblies.

“Gas vesicles are cylindrical tubes closed by conical end caps,” Li said. “They provide buoyancy within the cells of their native hosts.”

Blood analysis predicts sepsis and organ failure in children

Photo Credit: Edward Jenner

University of Queensland researchers have developed a method to predict if a child is likely to develop sepsis and go into organ failure.

Associate Professor Lachlan Coin from UQ’s Institute for Molecular Bioscience said sepsis was a life-threatening condition where a severe immune response to infection causes organ damage.

“Our research involved more than 900 critically ill children in the emergency departments and intensive care units of four Queensland hospitals,” Dr Coin said.

“Blood samples were taken from these patients at the acute stage of their infection, and we analyzed which genes were activated or deactivated.

“We were able to identify patterns of gene expression which could predict whether the child would develop organ failure within the next 24 hours, as well as whether the child had a bacterial or viral infection or a non-infectious inflammatory syndrome.”

Professor Luregn Schlapbach from UQ’s Child Health Research Centre said sepsis is best treated when recognized early, so the finding could help clinicians in the future.

Messenger RNAs with multiple “tails” could lead to more effective therapeutics

Graphic showing scientists adding "tails" to mRNA molecules
Illustration Credit: Catherine Boush, Broad Communications

Scientific Frontline: "At a Glance" Summary

• Main Discovery: Researchers from the Broad Institute and MIT engineered a novel mRNA structure containing multiple poly(A) "tails" that significantly enhances molecular stability and translation efficiency.
• Methodology: The team chemically synthesized branched mRNA topologies and assessed their performance in human cells and murine models, including integration with CRISPR-Cas9 systems for gene editing.
• Key Data: The multi-tailed mRNA increased protein activity in cells by 5 to 20 times and sustained protein production in mice for 14 days, lasting two to three times longer than unmodified molecules.
• Significance: This innovation addresses the limitation of rapid mRNA degradation, allowing for sustained therapeutic effects at lower doses which minimizes the risk of toxic side effects.
• Future Application: Potential uses include long-lasting treatments for diseases requiring gene editing or protein replacement, such as therapeutic interventions for high cholesterol.
• Branch of Science: Biotechnology and Bioengineering
• Additional Detail: The study demonstrates that cellular translation machinery readily accepts synthetic, non-natural mRNA shapes, validating the potential for extensive chemical topological engineering.