How Botox enters our cells

Volodymyr M. Korkhov (left) and Richard Kammerer of the Center for Life Sciences at PSI have made important advances towards understanding how botulinum neurotoxin, botox for short, enters our nerve cells.
Photo Credit: © Paul Scherrer Institute PSI/Mahir Dzambegovic

Botulinum toxin A1, better known under the brand name Botox, is not only a popular cosmetic agent, but also a highly effective bacterial neurotoxin that – when carefully dosed – can be used as a drug. It blocks the transmission of signals from nerves to muscles: This can relax muscles under the skin, which in cosmetics is used to smooth facial features. It can also alleviate conditions that are caused by cramping muscles or faulty signals from nerves, such as spasticity, bladder weakness, or misalignment of the eyes. However, if the dose is too high, the use of Botox can be fatal due to paralysis of the respiratory muscles. This can happen as a result of bacterial meat poisoning and is called botulism.

To make the most effective use of botulinum toxin as a drug, to precisely control its action, and to expand the range of possible applications of the toxin, researchers want to better understand how the toxin enters nerve cells to exert its effect. Until now, little was known about this.  “This is mainly because we had no structural data on what the toxin looks like in its full-length form when binding to its nerve cell's receptor,” says Richard A. Kammerer of the PSI Center for Life Sciences. So far there had only been studies on the structure of individual domains of the toxin – that is, specific parts of its complex molecular structure – and on the structure of such domains in complex with the receptor or one of its domains. 

Discovery of unexpected collagen structure could ‘reshape biomedical research’

Jeffrey Hartgerink is a professor of chemistry and bioengineering at Rice.
Photo Credit: Courtesy of Jeffrey Hartgerink / Rice University

Collagen, the body’s most abundant protein, has long been viewed as a predictable structural component of tissues. However, a new study led by Rice University’s Jeffrey Hartgerink and Tracy Yu, in collaboration with Mark Kreutzberger and Edward Egelman at the University of Virginia (UVA), challenges that notion, revealing an unexpected confirmation in collagen structure that could reshape biomedical research.

The researchers used advanced cryo-electron microscopy (cryo-EM) to determine the atomic structure of a packed collagen assembly that deviates from the traditionally accepted right-handed superhelical twist. Published in ACS Central Science, the study suggests collagen’s structural diversity may be greater than previously believed.

“This work fundamentally changes how we think about collagen,” said Hartgerink, professor of chemistry and bioengineering. “For decades, we have assumed that collagen triple helices always follow a strict structural paradigm. Our findings show that collagen assemblies can adopt a wider range of conformations than previously thought.”

OHSU researchers identify protective properties of amniotic fluid

A multidisciplinary team of OHSU researchers collaborates to better understand the mechanism of amniotic fluid’s role in fetal development. Their goal is to identify how its properties can be harnessed to address prenatal health concerns.
Photo Credit: Christine Torres Hicks/OHSU

Researchers at Oregon Health & Science University have made new discoveries about amniotic fluid, a substance historically not well understood in medical research due to the difficulty in obtaining it during pregnancy, especially across gestation.

Amniotic fluid is the vital fluid that surrounds and protects a fetus during pregnancy. In addition to providing much-needed cushion and protection for the fetus, it also aids in development of vital organs — especially the lungs, digestive tract and skin— and stabilizes the temperature inside the womb.

The new study, published in the journal Research and Practice in Thrombosis and Haemostasis, found that the addition of amniotic fluid to plasma — the liquid portion of blood — improves the blood’s ability to thicken and clot, which is a critical and likely a protective function throughout pregnancy and during delivery for both the birthing parent and the baby.

The mechanism of amniotic fluid’s role in fetal development is not well understood and is understudied: The OHSU study is one of the first to identify how the features and properties of amniotic fluid change over time, especially those properties that play a role in thickening the blood, and how those changes can affect how maternal blood coagulates. If a pregnant person’s blood does not clot properly, it can create life-threatening complications for the fetus and birthing parent, including excessive bleeding during pregnancy and delivery.  

Nerve Stimulation: the Brain is Not Always Listening

A small device worn on the body can stimulate the nervous system via electrodes on the ear.
Image Credit: Courtesy of Technische Universität Wien

Nerve stimulation can help with various diseases. However, this only works well if the body's own rhythms are taken into account, says a study by TU Wien (Vienna).

It doesn't always have to be medication. Some health problems, from chronic pain and inflammation to neurological diseases, can also be treated by nerve stimulation, for example with the help of electrodes that are attached to the ear and activate the vagus nerve. This method is sometimes referred to as an ‘electric pill’.

However, vagus nerve stimulation does not always work the way it is supposed to. A study conducted by TU Wien (Vienna) in cooperation with the Vienna Private Clinic now shows how this can be improved: Experiments demonstrate that the effect is very good when the electrical stimulation is synchronized with the body's natural rhythms – the actual heartbeat and breathing.

OHSU researchers use AI machine learning to map hidden molecular interactions in bacteria

Andrew Emili, Ph.D., professor of systems biology and oncological sciences, works in his lab at OHSU. Emili is part of a multi-disciplinary research team that uncovered how small molecules within bacteria interact with proteins, revealing a network of molecular connections that could improve drug discovery and cancer research.
Photo Credit: OHSU/Christine Torres Hicks

A new study from Oregon Health & Science University has uncovered how small molecules within bacteria interact with proteins, revealing a network of molecular connections that could improve drug discovery and cancer research.

The work also highlights how methods and principles learned from bacterial model systems can be applied to human cells, providing insights into how diseases like cancer emerge and how they might be treated. The results are published today in the journal Cell.

The multi-disciplinary research team, led by Andrew Emili, Ph.D., professor of systems biology and oncological sciences in the OHSU School of Medicine and OHSU Knight Cancer Institute, alongside Dima Kozakov, Ph.D., professor at Stony Brook University, studied Escherichia coli, or E. coli, a simple model organism, to map how metabolites — small molecules essential for life — interact with key proteins such as enzymes and transcription factors. These interactions control important processes such as cell growth, division and gene expression, but how exactly they influence protein function is not always clear.

T cells rise up to fight infections in the gut

An image produced through Xenium analysis of mouse small intestines. Protruding “villi” stick up from the lining of the small intestine. Valley-like “crypts” fill in the gaps.
Image Credit: Reina Lab, La Jolla Institute for Immunology

Your gut is a battleground. The cells that line your small intestine have to balance two seemingly contradictory jobs: absorbing nutrients from food, while keeping a wary eye out for pathogens trying to invade your body.

“This is a surface where pathogens can sneak in,” says La Jolla Institute for Immunology (LJI) Assistant Professor Miguel Reina-Campos, Ph.D. “That’s a massive challenge for the immune system.”

So how do immune cells keep the gut safe? New research led by scientists at LJI, UC San Diego, and the Allen Institute for Immunology shows that pathogen-fighting immune cells called tissue-resident memory CD8 T cells (TRM cells) go through a surprising transformation—and relocation—as they fight infections in the small intestine.

In fact, these cells literally rise up higher in the tissue to fight infections before pathogens can spread to deeper, more vulnerable areas.

New study identifies how blood vessel dysfunction can worsen chronic disease

OHSU researchers have uncovered how specialized cells surrounding small blood vessels, known as perivascular cells, contribute to blood vessel dysfunction in chronic diseases such as cancer, diabetes and fibrosis. The findings could change how these diseases are treated.
Photo Credit: OHSU/Christine Torres Hicks

Researchers at Oregon Health & Science University have uncovered how specialized cells surrounding small blood vessels, known as perivascular cells, contribute to blood vessel dysfunction in chronic diseases such as cancer, diabetes and fibrosis. The findings, published in Science Advances, could change how these diseases are treated.

The study, led by Luiz Bertassoni, D.D.S., Ph.D., founding director of the Knight Cancer Precision Biofabrication Hub and a professor at the OHSU Knight Cancer Institute and the OHSU School of Dentistry, shows that perivascular cells sense changes in nearby tissues and send signals that disrupt blood vessel function, worsening disease progression.

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.

Discovery of how limiting damage from an asthma attack could stop disease

Scientists at King’s have discovered a new cause for asthma that sparks hope for treatment that could prevent the life-threatening disease.
Image Credit: Copilot DALL-E 3 AI Generated

Most current asthma treatments stem from the idea that it is an inflammatory disease. Yet, the life-threatening feature of asthma is the attack or the constriction of airways, making breathing difficult. A new study, published in the journal Science, shows for the first time that many features of an asthma attack—inflammation, mucus secretion, and damage to the airway barrier that prevents infections - result from this mechanical constriction in a mouse model.

The findings suggest that blocking a process that normally causes epithelial cell death could prevent the damage, inflammation, and mucus that result from an asthma attack.

Professor Jody Rosenblatt from the School of Basic & Medical Biosciences said: “Our discovery is the culmination of more than ten years of work. As cell biologists who watch processes, we could see that the physical constriction of an asthma attack causes widespread destruction of the airway barrier. Without this barrier, asthma sufferers are far more likely to get long-term inflammation, wound healing, and infections that cause more attacks. By understanding this fundamental mechanism, we are now in a better position to prevent all these events.”

The Rotisserie-Inspired Device That Could Revolutionize Cancer Surgery

The Zavaleta Lab’S Raman Rotisserie Device Creates a Map of the Surface of a Resected Tumor to Aid Surgeons in the Operating Room.
Photo Credit: Alex Czaja

Like many Texans, Cristina Zavaleta grew up enjoying the culinary delights of the state’s famous smokehouse BBQs. She couldn’t have imagined that those humble rotisseries of her childhood would one day inspire a game-changing device for the operating room that could help surgeons prevent tumor recurrence.

On a team excursion to Disneyland, the WiSE Gabilan Assistant Professor of Biomedical Engineering and her students were reminded of rotisseries when they encountered a food vendor at the Star Wars-themed land, Galaxy’s Edge. It was a lightbulb moment. The rotisserie configuration was a perfect way of intricately scanning excised tumors, with the help of the Zaveleta Lab’s unique nanoparticles, to light up where the cancerous tissue may not have been entirely removed from the patient. Surgeons could then be guided to precisely remove the remaining tumor, all while the patient is still under anesthesia. The result would reduce the need for traumatic repeat surgeries and potential cancer recurrence and metastasis.

Zavaleta and her team built the device, which they dubbed the Raman Rotisserie. It physically rotates a tumor specimen and works in conjunction with an imaging technique known as Raman spectroscopy, which scans the surface of the excised tumor. Their research, which aims to improve the success rate of breast cancer lumpectomies, has now been published in NPJ Imaging.

Autism and ADHD are linked to disturbed gut flora very early in life

The researchers have found links between the gut flora in babies first year of life and future diagnoses.
Photo Credit: Cheryl Holt

Disturbed gut flora during the first years of life is associated with diagnoses such as autism and ADHD later in life. This is according to a study led by researchers at the University of Florida and Linköping University and published in the journal Cell.

The study is the first forward-looking, or prospective, study to examine gut flora composition and a large variety of other factors in infants, in relation to the development of the children's nervous system. The researchers have found many biological markers that seem to be associated with future neurological development disorders, such as autism spectrum disorder, ADHD, communication disorder and intellectual disability.

“The remarkable aspect of the work is that these biomarkers are found at birth in cord blood or in the child’s stool at one year of age over a decade prior to the diagnosis,” says Eric W Triplett, professor at the Department of Microbiology and Cell Science at the University of Florida, USA, one of the researchers who led the study.

Pollen is a promising sustainable tool in the bone regeneration process

Scientists have used pollen to grow hydroxyapatite capsules, so the mineral can better support bone regeneration
Photo Credit: Alex Jones

A study has shown pollen grains can be used as green templates for producing biomaterials, showcasing their potential to support drug delivery and bone regeneration.

With an increasingly ageing population, bone fractures are becoming more common. Bone is generally able to self-repair but if the fracture is too big or the person affected too fragile, as for example people with osteoporosis, the use of bone fillers can help.

Hydroxyapatite (HAp) is an inorganic mineral present in human bone and teeth, which can be used to support bone regeneration. It makes up somewhere between 65 per cent and 70 per cent of the weight of human bone. Healthcare professionals often use synthetic and natural HAp when carrying out bone repair treatments.

A team at the University of Portsmouth has worked with international colleagues to explore sustainable ways to improve the process. 

They examined the feasibility of using pollen grains as bio-templates for growing calcium phosphate minerals in the lab - particularly hydroxyapatite (HAp) and β-tricalcium phosphate (TCP), which are types of calcium phosphate used for bone repair.