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. 

Purdue biochemists discover self-repair function in key photosynthetic protein complex

Sujith Puthiyaveetil and Steve McKenzie look at a plant thylakoid in a lab at the biochemistry building at Purdue University.
Photo Credit: Purdue Agricultural Communications/Joshua Clark

Cyanobacteria began contributing oxygen to Earth’s mostly noxious atmosphere more than 2 billion years ago. The photosystem II protein complex now shared by various lineages of cyanobacteria, algae and land plants has served as a major site of oxygen production throughout the history of life on Earth ever since.

Ironically, receiving too much light can damage photosystem II and erode the photosynthetic efficiency of plants. Purdue University biochemists Steven McKenzie and Sujith Puthiyaveetil have gleaned new, long-hidden details about how photosystem II repairs itself. McKenzie and Puthiyaveetil’s findings have been published in the journal Plant Communications.

“The photosystem II splits water and extracts electrons and protons, leaving oxygen as a by-product. Photosystem II thereby powers life on Earth,” said Puthiyaveetil, associate professor of biochemistry. Even so, “it’s still fairly poorly understood how these huge protein complexes that use light energy to produce oxygen are able to be repaired and maintained so efficiently across different lineages of plants, algae and cyanobacteria.”

Research in Fruit Flies Pinpoints Brain Pathways Involved in Alcohol-Induced Insomnia

Adrian Rothenfluh, PhD (left), and Maggie Chvilicek (right), authors on the recent study.
Photo Credit: Courtesy of University of Utah Health

Alcohol use disorder, which affects over 10% of Americans, can lead to persistent and serious insomnia. Difficulties falling asleep and staying asleep can last even after months of sobriety, increasing the risk of relapse. But treating withdrawal-related insomnia is difficult, partly because what’s going on in the brain in this condition remains largely mysterious.

 Now, research in fruit flies has identified specific brain signals and groups of brain cells that are involved in alcohol-induced insomnia. This work could ultimately lead to targeted treatments for alcohol-related sleep loss, helping people recover from alcohol use disorder.

  “The effects of alcohol on sleep seem to be localized to a particular cell type in the brain, which is not something that’s ever been shown before,” says Maggie Chvilicek, graduate researcher in neuroscience at the University of Utah and lead author on the study. She adds that these cells often do similar things in flies and humans. “The mechanism that we identified is something that very likely could also exist in a mammalian brain.”

Native bee populations can bounce back after honey bees move out

A native bee sits on a purple flower on the left, while a honey bee sits on a yellow flower on the right.  Photo Credit: © Margarita López-Uribe

Managed honey bees have the potential to affect native bee populations when they are introduced to a new area, but a study led by researchers at Penn State suggests that, under certain conditions, the native bees can bounce back if the apiaries are moved away.

The research, published in the Journal of Insect Science, examined the effects of migratory beekeeping — the practice of moving honey bee colonies to a different location for part of the year — on native bee populations. 

The researchers found that when managed honey bees were moved into an area, the population of native bees decreased in abundance and diversity. However, in places where apiaries were kept for years and then removed, the native bee populations once again increased in both total numbers and species diversity.

Margarita López-Uribe, the Lorenzo L. Langstroth Early Career Professor of Entomology in the College of Agricultural Sciences and co-author of the paper, said the findings suggest that while migratory beekeeping can be a disturbance to native bees, it may also be possible for those populations to recover.

Quantum mechanics helps with photosynthesis

First author Erika Keil and Prof. Jürgen Hauer in the lab.
Photo Credit: Andreas Heddergott / TUM

Photosynthesis - mainly carried out by plants - is based on a remarkably efficient energy conversion process. To generate chemical energy, sunlight must first be captured and transported further. This happens practically loss-free and extremely quickly. A new study by the Chair of Dynamic Spectroscopy at the Technical University of Munich (TUM) shows that quantum mechanical effects play a key role in this process. A team led by Erika Keil and Prof. Jürgen Hauer discovered this through measurements and simulations.

The efficient conversion of solar energy into storable forms of chemical energy is the dream of many engineers. Nature found a perfect solution to this problem billions of years ago. The new study shows that quantum mechanics is not just for physicists but also plays a key role in biology.

Photosynthetic organisms such as green plants use quantum mechanical processes to harness the energy of the sun, as Prof. Jürgen Hauer explains: “When light is absorbed in a leaf, for example, the electronic excitation energy is distributed over several states of each excited chlorophyll molecule; this is called a superposition of excited states. It is the first stage of an almost loss-free energy transfer within and between the molecules and makes the efficient onward transport of solar energy possible. Quantum mechanics is therefore central to understanding the first steps of energy transfer and charge separation.”

Videos with Cold Symptoms Activate Brain Regions and Trigger Immune Response

 Study on Brain Activity and Antibody Concentration
Photo Credit: Andrea Piacquadio

People who watch videos of sneezing or sick people show increased activity in brain regions that represent an interface between the brain and the immune system and react to potential dangers. At the same time, the concentration of antibodies in their saliva increases. The findings of a study by researchers from the Department of Biology at the University of Hamburg indicate that an important part of the immune system responds even before a pathogen enters the body. The results were published in the journal Brain Behavior and Immunity.

Throughout human history, communicable diseases, especially viral respiratory infections such as SARS-CoV-2 or influenza, have been among the main factors that significantly influence human mortality. The constant threat of pathogen transmission has led to the development of various physiological mechanisms of the immune system - for example, the body releases proteins to fight pathogens in the body.

Regulatory T Cells Found to Safeguard Brain Health, Memory Formation

Differences in neuronal activation in mice with intact Tregs (left) and depleted Tregs (right). The finding demonstrates that Tregs play a role in ensuring healthy neuronal activity under normal conditions.
Image Credit: Mathis/Benoist Lab

Immune cells called regulatory T cells have long been known for their role in countering inflammation. In the setting of infection, these so-called Tregs restrain the immune system to ensure it doesn’t go into overdrive and mistakenly attack the body’s own organs.

Now scientists at Harvard Medical School have discovered a distinct population of Tregs dwelling in the protective layers of the brains of healthy mice with a repertoire much broader than inflammation control.

The research, published Jan. 28 in Science Immunology, shows that these specialized Tregs not only control access to the inner regions of the brain but also ensure the proper renewal of nerve cells in an area of the brain where short-term memories are formed and stored.

The research, funded in part by the National Institutes of Health, represents an important step toward untangling the complex interplay of immune cells in the brain. If replicated in further animal studies and confirmed in humans, the research could open up new avenues for averting or mitigating disease-fueling inflammation in the brain.

A genome-wide atlas of cell morphology reveals gene functions

Human cells imaged using Cell Painting. Cell nuclei are shown in blue, actin filaments in yellow, the endoplasmic reticulum in magenta, golgi bodies in cyan, and mitochondria in green.
Image Credit: Maria Lozada, Neal Lab

Visualizing cells after editing specific genes can help scientists learn new details about the function of those genes. But using microscopy to do this at scale can be challenging, particularly when studying thousands of genes at a time.

Now, researchers at the Broad Institute of MIT and Harvard, along with collaborators at Calico Life Sciences, have developed an approach that brings the power of microscopy imaging to genome-scale CRISPR screens in a scalable way. 

PERISCOPE — which stands for perturbation effect readout in situ via single-cell optical phenotyping — combines two technologies developed by Broad scientists: Cell Painting, which can capture images and key measures of subcellular compartments at scale, and Optical Pooled Screening, which “barcodes” cells and uses CRISPR to systematically turn off individual genes to study their function in those cells. 

The new technique lets scientists study the effects of perturbing over 20,000 genes on hundreds of image-based cellular features. Generating data with this method is more than 10 times less expensive than comparable high-dimensional approaches such as high-throughput single-cell RNA sequencing and can be adapted to study a wide variety of cell types. In Nature Methods, the researchers applied PERISCOPE to execute three whole-genome CRISPR screens to create an open-source atlas of cell morphology.

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.

Researchers create lab model that could lead to new, non-hormonal birth control methods

Oregon Health & Science University researchers have developed a new lab model to study how changes in cervical mucus during the menstrual cycle help regulate fertility. This model could help develop new, non-hormonal birth control methods for women.
Photo Credit: OHSU/Christine Torres Hicks

Oregon Health & Science University researchers have developed a new lab model to study how changes in cervical mucus during the menstrual cycle help regulate fertility. This model could help develop new, non-hormonal birth control methods for women.

The study, published in the journal Biology of Reproduction, is part of ongoing work by senior author Leo Han, M.D., M.P.H., associate professor of obstetrics and gynecology in the OHSU School of Medicine and the OHSU Oregon National Primate Research Center. Han is a complex family planning specialist whose research focuses on developing new, non-hormonal contraceptives. 

In this study, his research team analyzed the genetic activity in lab-cultured cervical cells, identifying hundreds of different genes that could be drug targets for birth control that uses innovative new methods to block sperm. 

Polygamy is (not) for the birds

Rafael S. Marcondes, a faculty fellow in ecology and evolutionary biology at Rice
Photo Credit: Alex Becker/Rice University

Researchers at Rice University have uncovered new insights into the evolution of bird behavior, revealing why certain mating systems persist while others disappear over time. In a recent paper published in the journal Evolution, Rafael S. Marcondes and Nicolette Douvas reveal that lekking — a mating system where males display for females without forming lasting bonds — is an evolutionarily stable strategy. In contrast, resource-defense polygamy, where one sex — usually but not always the male — guards territories to attract mates, is highly unstable and often reverts to monogamy.

“This research not only examines how mating behaviors influence species survival but also sheds light on larger evolutionary questions,” said Marcondes, the corresponding author and a faculty fellow in ecology and evolutionary biology at Rice. “By studying birds, we’re uncovering principles that may resonate across other species too.”

The study analyzed data from more than 60% of the world’s bird species — approximately 6,620 species — making it one of the most comprehensive analyses of its kind.

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.

New sunflower family tree reveals multiple origins of flower symmetry

A new sunflower family tree reveals that flower symmetry evolved multiple times independently. Chrysanthemum lavandulifolium, on the upper left, and Artemisia annua, upper right, are closely related species from the same tribe; the former has bilaterally symmetric flowers — the rays — and the latter does not. Rudbeckia hirta, lower left, from the sunflower tribe has bilaterally symmetric flowers, and Eupatorium chinense, lower right, from the Eupatorieae tribe does not; these two tribes are closely related groups. A sunflower, center, shows flowers with bilateral symmetry — the large petal-like flowers in the outer row — and without bilateral symmetry — the small flowers in the inner rows.
Photo Credits: Guojin Zhang, Ma laboratory / Pennsylvania State University
(CC BY-NC-ND 4.0 DEED)

The sunflower family tree revealed that flower symmetry evolved multiple times independently, a process called convergent evolution, among the members of this large plant family, according to a new analysis. The research team, led by a Penn State biologist, resolved more of the finer branches of the family tree, providing insight into how the sunflower family — which includes asters, daisies and food crops like lettuce and artichoke — evolved.

A paper describing the analysis and findings, which researchers said may help identify useful traits to selectively breed plants with more desirable characteristics is available online and will be published in an upcoming print edition of the journal Plant Communications.

“Convergent evolution describes the independent evolution of what appears to be the same trait in different species, like wings in birds and bats,” said Hong Ma, Huck Chair in Plant Reproductive Development and Evolution, professor of biology in the Eberly College of Science at Penn State and the leader of the research team. “This can make it difficult to determine how closely related two species are by comparing their traits, so having a detailed family tree based on DNA sequence is crucial to understanding how and when these traits evolved.”

Scientists identify rare gene variants which confer up to 6-fold increase in risk of obesity

Photo Credit: Mart Production

The discovery of rare variants in the genes BSN and APBA1 are some of the first obesity-related genes identified for which the increased risk of obesity is not observed until adulthood.

The study, published in Nature Genetics, was led by researchers at the Medical Research Council (MRC) Epidemiology Unit and the MRC Metabolic Diseases Unit at the Institute of Metabolic Science, both based at the University of Cambridge.

The researchers used UK Biobank and other data to perform whole exome sequencing of body mass index (BMI) in over 500,000 individuals.

They found that genetic variants in the gene BSN, also known as Bassoon, can raise the risk of obesity as much as six times and was also associated with an increased risk of non-alcoholic fatty liver disease and of type 2 diabetes.

The Bassoon gene variants were found to affect 1 in 6,500 adults, so could affect about 10,000 people in the UK.

Discovery of how COVID-19 virus replicates opens door to new antiviral therapies

A new study, looking at the replication stage of the SARS-CoV-2 virus that causes COVID-19, discovered important mechanisms in its replication that could be the foundation for new antiviral therapies.
Image Credit: Gerd Altmann

The study, which sets out to investigate how the SARS-CoV-2 virus replicates once it enters the cells, has made surprising discoveries that could be the foundation for future antiviral therapies. It also has important theoretical implications as the replication of the SARS-CoV-2 virus has, so far, received less attention from researchers.

The viral life cycle can be broken down into two main stages: the first stage is where the virus enters the cell. The second stage is replication where the virus uses the molecular machinery of the cell it has infected to replicate itself by building its parts, assembling them into new viruses that can then exit to infect other cells.

The majority of research into SARS-CoV-2 – the causative agent of COVID-19 – has focused on the Spike protein that allows viral entry. This has led to a lack of understanding of how the virus replicates once it has entered the cell.

A new paper led by Dr Jeremy Carlton in collaboration with Dr David Bauer at the Francis Crick Institute, focuses on how the Envelope protein of SARS-CoV-2 controls late stages of viral replication.

Pressure determines which embryonic cells become ‘organizers’

 Tooth epithelium (cell surface; yellow) and mesenchyme (cell surface; magenta). Proliferating cells (cyan) expand the tissue, generating a mechanical pressure at the tissue center that drives the formation of the main tooth signaling center or organizer, the enamel knot.
Photo Credit Neha Pincha Shroff and Pengfei Xu

A collaboration between research groups at the University of California, TU Dresden in Germany and Cedars-Sinai Guerin Children’s in Los Angeles has identified a mechanism by which embryonic cells organize themselves to send signals to surrounding cells, telling them where to go and what to do. While these signaling centers have been known to science for a while, how individual cells turn into organizers has been something of a mystery.

Until now. In a paper published in the journal Nature Cell Biology, the researchers find that cells are literally pressed into becoming organizers.

“We were able to use microdroplet techniques to figure out how the buildup of mechanical pressure affects organ formation,” said co-corresponding author Otger Campàs, former associate professor of mechanical engineering at UC Santa Barbara, who is currently managing director, professor and chair of tissue dynamics at the Physics of Life Excellence Cluster of TU Dresden.

Discovery could end global amphibian pandemic

Panamanian golden frog
Photo Credit: Brian Gratwicke/U.S. Fish & Wildlife Service

A fungus devastating frogs and toads on nearly every continent may have an Achilles heel. Scientists have discovered a virus that infects the fungus, and that could be engineered to save the amphibians.

The fungus, Batrachochytrium dendrobatidis or Bd, ravages the skin of frogs and toads, and eventually causes heart failure. To date it has contributed to the decline of over 500 amphibian species, and 90 possible extinctions including yellow-legged mountain frogs in the Sierras and the Panamanian golden frog. 

A new paper in the journal Current Biology documents the discovery of a virus that infects Bd, and which could be engineered to control the fungal disease.

The UC Riverside researchers who found the virus are excited about the implications of their discovery. In addition to helping them learn about how fungal pathogens rise and spread, it offers the hope of ending what they call a global amphibian pandemic. 

“Frogs control bad insects, crop pests, and mosquitoes. If their populations all over the world collapse, it could be devastating,” said UCR microbiology doctoral student and paper author Mark Yacoub. 

“They’re also the canary in the coal mine of climate change. As temperatures get warmer, UV light gets stronger, and water quality gets worse, frogs respond to that. If they get wiped out, we lose an important environmental signal,” Yacoub said. 

In the evolution of walking, the hip bone connected to the rib bones

New reconstruction of the skeleton of Tiktaalik roseae, a 375-million-year-old fossil fish. In a new study, researchers used micro-CT imaging to reveal vertebrae and ribs of the fish that were previously hidden beneath rock. The new reconstruction shows that the fish’s ribs likely attached to its pelvis, an innovation thought to be crucial to supporting the body and for the eventual evolution of walking.
Photo Credit: Thomas Stewart / Pennsylvania State University
(CC BY-NC-ND 4.0 DEED)

Before the evolution of legs from fins, the axial skeleton — including the bones of the head, neck, back and ribs — was already going through changes that would eventually help our ancestors support their bodies to walk on land. A research team including a Penn State biologist completed a new reconstruction of the skeleton of Tiktaalik, the 375-million-year-old fossil fish that is one of the closest relatives to limbed vertebrates. The new reconstruction shows that the fish’s ribs were likely attached to its pelvis, an innovation thought to be crucial to supporting the body and for the eventual evolution of walking.

A paper describing the new reconstruction, which used microcomputed tomography (micro-CT) to scan the fossil and reveal vertebrae and ribs of the fish that were previously hidden beneath rock, appeared in the journal Proceedings of the National Academy of Sciences.

“Tiktaalik was discovered in 2004, but key parts of its skeleton were unknown,” said Tom Stewart, assistant professor of biology in the Eberly College of Science at Penn State and one of the leaders of the research team. “These new high-resolution micro-CT scans show us the vertebrae and ribs of Tiktaalik and allow us to make a full reconstruction of its skeleton, which is vital to understanding how it moved through the world.”

Scientists link certain gut bacteria to lower heart disease risk

Rod-shaped Oscillibacter sp. bacteria take up fluorescently labeled cholesterol (here shown in green).
Image Credit: Ahmed Mohamed 

Changes in the gut microbiome have been implicated in a range of diseases including type 2 diabetes, obesity, and inflammatory bowel disease. Now, a team of researchers at the Broad Institute of MIT and Harvard along with Massachusetts General Hospital has found that microbes in the gut may affect cardiovascular disease as well. In a study published in Cell, the team has identified specific species of bacteria that consume cholesterol in the gut and may help lower cholesterol and heart disease risk in people.

Members of Ramnik Xavier’s lab, Broad’s Metabolomics Platform, and collaborators analyzed metabolites and microbial genomes from more than 1,400 participants in the Framingham Heart Study, a decades-long project focused on risk factors for cardiovascular disease. The team discovered that bacteria called Oscillibacter take up and metabolize cholesterol from their surroundings, and that people carrying higher levels of the microbe in their gut had lower levels of cholesterol. They also identified the mechanism the bacteria likely use to break down cholesterol. The results suggest that interventions that manipulate the microbiome in specific ways could one day help decrease cholesterol in people. The findings also lay the groundwork for more targeted investigations of how changes to the microbiome affect health and disease.

“Our research integrates findings from human subjects with experimental validation to ensure we achieve actionable mechanistic insight that will serve as starting points to improve cardiovascular health,” said Xavier, who is a core institute member, director of the Immunology Program, and co-director of the Infectious Disease and Microbiome Program at the Broad. He is also a professor at Harvard Medical School and Massachusetts General Hospital.