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. 

Research Pinpoints Weakness in Lung Cancer’s Defenses

A microscope image of lung cancer cells (purple) containing the activated form of a metabolic enzyme called GUK1 (brown) that supports cancer growth.
Image Credit: Haigis lab

Lung cancer is a particularly challenging form of cancer. It often strikes unexpectedly and aggressively with little warning, and it can shapeshift in unpredictable ways to evade treatment.

While researchers have gleaned important insights into the basic biology of lung cancer, some of the disease’s molecular maneuvers have remained elusive.

Now, a team led by scientists at Harvard Medical School has made strides in understanding how a genetic flaw in some lung cancers alters cancer cell metabolism to fuel the disease.

Working with mouse models and human cancer cells, the researchers identified a metabolic enzyme called GUK1 in lung cancers harboring an alteration in the ALK gene. Their experiments showed that GUK1 plays an important role in boosting metabolism in tumor cells to help them grow.

The findings, reported in Cell and supported in part by federal funding, provide a clearer picture of how metabolism works in lung cancer.

The research could set the stage for developing therapies that target GUK1 to curb cancer growth, the team said.

Women of Science: A Legacy of Achievement

Future generations to pursue their passions and break down barriers in the pursuit of knowledge.
Image Credit: Scientific Frontline stock image

Throughout history, women have made groundbreaking contributions to science, despite facing significant societal barriers and a lack of recognition. Their relentless pursuit of knowledge and innovation has shaped our understanding of the world and paved the way for future generations of scientists. This article celebrates the achievements of some of these remarkable women, highlighting their struggles and the impact of their work.

The women featured in this article, along with countless others throughout history, have made invaluable contributions to the advancement of science. Their achievements, often accomplished in the face of adversity and societal barriers, have shaped our understanding of the world and paved the way for future generations of scientists. These women demonstrate the power of perseverance, the importance of challenging established norms, and the profound impact that individual dedication can have on scientific progress. By recognizing and celebrating their legacies, we not only honor their contributions but also inspire future generations to pursue their passions and break down barriers in the pursuit of knowledge.

Spliceosome: How Cells Avoid Errors When Manufacturing Mrna

Quality control during splicing: When an error in the precursor mRNA is detected, the spliceosome is blocked, the recruited control factors interrupt the “normal” cycle, and a molecular short circuit causes the spliceosome to disassemble.
Image Credit: © K. Wild, K. Soni, I. Sinning

A complex molecular machine, the spliceosome, ensures that the genetic information from the genome, after being transcribed into mRNA precursors, is correctly assembled into mature mRNA. Splicing is a basic requirement for producing proteins that fulfill an organism’s vital functions. Faulty functioning of a spliceosome can lead to a variety of serious diseases. Researchers at the Heidelberg University Biochemistry Center (BZH) have succeeded for the first time in depicting a faultily “blocked” spliceosome at high resolution and reconstructing how it is recognized and eliminated in the cell. The research was conducted in collaboration with colleagues from the Australian National University.

Chemical looping turns environmental waste into fuel

As scientists search for sustainable alternatives to typical waste disposal methods, chemical looping technology promises to spawn a new energy cycle.
Photo Credit: Chokniti Khongchum

Turning environmental waste into useful chemical resources could solve many of the inevitable challenges of our growing amounts of discarded plastics, paper and food waste, according to new research. 

In a significant breakthrough, researchers from The Ohio State University have developed a technology to transform materials like plastics and agricultural waste into syngas, a substance most often used to create chemicals and fuels like formaldehyde and methanol. 

Using simulations to test how well the system could break down waste, scientists found that their approach, called chemical looping, could produce high-quality syngas in a more efficient manner than other similar chemical techniques. Altogether, this refined process saves energy and is safer for the environment, said Ishani Karki Kudva, lead author of the study and a doctoral student in chemical and biomolecular engineering at Ohio State. 

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.

First-of-its-kind integrated dataset enables genes-to-ecosystems research

DOE national laboratory scientists led by Oak Ridge National Laboratory have developed the first tree dataset of its kind, bridging molecular information about the poplar tree microbiome to ecosystem-level processes.
Illustration Credit: Andy Sproles/ORNL, U.S. Dept. of Energy

The first-ever dataset bridging molecular information about the poplar tree microbiome to ecosystem-level processes has been released by a team of Department of Energy scientists led by Oak Ridge National Laboratory. The project aims to inform research regarding how natural systems function, their vulnerability to a changing climate, and ultimately how plants might be engineered for better performance as sources of bioenergy and natural carbon storage.

The data, described in Nature Publishing Group’s Scientific Data, provides in-depth information on 27 genetically distinct variants, or genotypes, of Populus trichocarpa, a poplar tree of interest as a bioenergy crop. The genotypes are among those that the ORNL-led Center for Bioenergy Innovation previously included in a genome-wide association study linking genetic variations to the trees’ physical traits. ORNL researchers collected leaf, soil and root samples from poplar fields in two regions of Oregon — one in a wetter area subject to flooding and the other drier and susceptible to drought. 

Details in the newly integrated dataset range from the trees’ genetic makeup and gene expression to the chemistry of the soil environment, analysis of the microbes that live on and around the trees and compounds the plants and microbes produce.

The dataset “is unprecedented in its size and scope,” said ORNL Corporate Fellow Mitchel Doktycz, section head for Bioimaging and Analytics and project co-lead. “It is of value in answering many different scientific questions.” By mining the data with machine learning and statistical approaches, scientists can better understand how the genetic makeup, physical traits and chemical diversity of Populus relate to processes such as cycling of soil nitrogen and carbon, he said. 

Cystic fibrosis: why infections persist despite therapy

The anchor points present on the surface of the airways in cystic fibrosis (left image, in red) decrease when the balance between the two cell signaling pathways is restored (right image).
Image Credit: Marc Chanson et al, 2024

Cystic fibrosis is a genetic disease that causes serious and sometimes fatal respiratory and digestive disorders. A new treatment, available since 2020, improves lung function and quality of life. However, it does not always eradicate the bacteria responsible for respiratory infections. By studying 3D models of human lung cells, scientists at the University of Geneva (UNIGE) discovered that this drug does not prevent the development on the surface of the respiratory tract of ''docking stations'' to which bacteria attach themselves to infect the body. These docking stations result from a disruption in the signals involved in cell development in the respiratory system. By combining the current treatment with other molecules, it may be possible to restore cell balance and thus better prevent bacterial infections. These results are published in the American Journal of Respiratory Cell and Molecular Biology.

Cystic fibrosis is the most common genetic disease. Each year, it affects one in every 3,300 newborns in Switzerland. Mutations in the gene responsible for the CFTR protein cause the secretion of excessively thick mucus, which obstructs the airways. Although a triple therapy, available in Switzerland since 2020, has improved the quality of life of people with cystic fibrosis, it is not suitable for all those affected and does not always prove effective.

Heat flows the secret to order in prebiotic molecular kitchen

Schematic visualization of heat flows in rock cracks.
Illustration Credit: Christof Mast

Life is complicated. What is true for our everyday existence also holds for the many complex processes that take place inside cells. Proteins constantly have to be synthesized, cell walls built, and DNA replicated. This can only work when reaction partners converge at the right time in sufficiently high concentrations while suffering little disruption from other substances. Over the course of billions of years, evolution has perfected these mechanisms and ensured that such vital processes occur with high efficiency at the correct place.

Circumstances were probably a lot more chaotic four billion years ago, when prebiotic reactions created the conditions for the emergence of the first lifeforms. For these reactions, too, it was necessary for the ‘right’ substances to be brought together at the ‘right’ time in one place, so that more complex biomolecules like RNA and amino acid chains could form. While such reactions are possible to recreate in the laboratory thanks to manual intermediate steps, it is highly challenging for them to come about in a simple ‘primordial soup’ – that is to say, a very dilute mixture of prebiotic building blocks. So how could nature create suitable conditions for the origin of life?

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.

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.