Binding power of trapped water demonstrated for the first time

Water molecules are a driving force in the formation of molecular bonds, such as in proteins.
Image Credit: INT, KIT

Water is everywhere – it covers most of the earth, circulates in the human body and can be found in even the smallest molecular niches. But what happens if water does not flow freely but is trapped in such structures? Researchers at the Karlsruhe Institute of Technology (KIT) and Constructor University in Bremen have proven for the first time that "locked" water can influence its environment and strengthen the bond between molecules. This finding could open new avenues for the development of drugs and materials.

Some of the water on Earth is found in tiny nooks and crannies – enclosed in molecular pockets, such as protein binding sites or synthetic receptors. Whether this water behaves neutrally in the presence of other molecules or influences their binding has so far been controversial. "Water molecules usually interact most strongly with each other. However, experimental data showed that water behaves unusually in such narrow pockets", says Dr. Frank Biedermann from KIT's Institute of Nanotechnology. "We have now been able to provide the theoretical basis for these observations and prove that the water in the molecular pockets is energetically tense."

Deciphering the mechanisms of genome size evolution

The sequencing of the genomes of a spider from the mainland (Dysdera catalonica, left) and one from the Canary Islands (Dysdera tilosensis, left) opens a new perspective for understanding how genome size evolves in similar species, an enigma that has baffled the scientific community for years.
Photo Credit: Courtesy of University of Barcelona

This study contradicts the more traditional evolutionary view — on island-colonizing species, whose genomes are larger and often have more repetitive elements — and expands the scientific debate on a major puzzle in evolutionary biology: how and why does genome size change during the evolution of living beings?

The study is led by Julio Rozas and Sara Guirao, experts from the Faculty of Biology and the Biodiversity Research Institute (IRBio) of the University of Barcelona. The paper, whose first author is Vadim Pisarenco (UB-IRBio), also involves teams from the University of La Laguna, the Spanish National Research Council (CSIC) and the University of Neuchâtel (Switzerland).

This research offers a surprising perspective to explain a phenomenon that has puzzled scientists for decades: the size of the genome — the total number of DNA base pairs encoding an organism’s genetic information — varies enormously between species, even those with similar biological complexity.

Fat particles could be key to treating metabolic brain disorders

For decades, it was widely accepted that neurons relied exclusively on glucose to fuel their functions in the brain. This is not the case.
Photo Credit: The University of Queensland

Evidence challenging the long-held assumption that neuronal function in the brain is solely powered by sugars has given researchers new hope of treating debilitating brain disorders.

A University of Queensland study led by Dr Merja Joensuu showed that neurons also use fats for fuel as they fire off the signals for human thought and movement.

“For decades, it was widely accepted that neurons relied exclusively on glucose to fuel their functions in the brain,” Dr Joensuu said.

“But our research shows fats are undoubtedly a crucial part of the neuron’s energy metabolism in the brain and could be a key to repairing and restoring function when it breaks down.”

Dr Joensuu from the Australian Institute for Bioengineering and Nanotechnology along with lab members PhD candidate Nyakuoy Yak and Dr Saber Abd Elkader from UQ’s Queensland Brain Institute set out to examine the relationship of a particular gene (DDHD2) to hereditary spastic paraplegia 54 (HSP54).

Key driver of pancreatic cancer spread identified

A 3D tumor vessel-on-a-chip model, showing pancreatic cancer cells (green) invading an engineered blood vessel (red) by breaking down the vascular basement membrane (yellow).
Image Credit: Courtesy of Lee Lab

A Cornell-led study has revealed how a deadly form of pancreatic cancer enters the bloodstream, solving a long-standing mystery of how the disease spreads and identifying a promising target for therapy.

Pancreatic ductal adenocarcinoma is among the most lethal cancers, with fewer than 10% of patients surviving five years after diagnosis. Its microenvironment is a dense, fibrotic tissue that acts like armor around the tumor. This barrier makes drug delivery difficult and should, in theory, prevent the tumor from spreading. Yet the cancer metastasizes with striking efficiency – a paradox that has puzzled scientists.

New research published in the journal Molecular Cancer reveals that a biological receptor called ALK7 is responsible, by activating two interconnected pathways that work in tandem. One makes cancer cells more mobile through a process called epithelial-mesenchymal transition, and the other produces enzymes that physically break down the blood vessel walls.

UCLA researchers find “protective switches” that may make damaged livers suitable for transplantation

 

Photo Credit: Sasin Tipchai

In a mouse model of liver transplantation, UCLA researchers have identified proteins that act as “protective switches” guarding the liver against damage occurring when blood supply is restored during transplantation, a process known as ischemia-reperfusion injury.

The finding could increase the supply of donor organs by using molecular therapies to strengthen the liver’s protective pathways. By boosting this protection,  organs that would otherwise be discarded as damaged or suboptimal could be made suitable for transplantation and added to the donor pool, said Kenneth J. Dery, Ph.D , an associate adjunct professor of surgery in the division of liver and pancreas transplantation at the David Geffen School of Medicine at UCLA and the study’s co-senior author.

“One of the most intractable problems in the field of organ transplantation remains the nationwide shortage of donor livers, which has led to high patient mortality while waiting for a liver transplant,” Dery said. “This could ultimately help address the national transplant shortage and lower mortality rates.”

Subtle cues between cells and immune system contribute to spread of cancer

Purdue University researcher John Tesmer is deciphering an intricate cell signaling system critical to immune response.
 Photo Credit: Alisha Willett / Purdue University

In the march of metastasis, a molecular trail of crumbs guides some cancer cells from the primary tumor to establish new colonies within the body. Blocking the cells’ ability to follow the trail might halt metastasis but could also meddle with an intricate cellular signaling system critical to immune response. Purdue University scientists are deciphering this signaling system to better understand how it could be used to address multiple diseases, including cancer.

Recent work, published in Nature, focused on a specific transaction inside the cell but is broadly applicable to how cells respond to signals from the endocrine system, a hormonal messaging system that influences metabolism, growth and reproduction and helps the body maintain homeostasis.

“There are multiple pathways inside a cell that are triggered by this messaging system and when they don’t work together properly, it promotes disease,” said research lead John Tesmer, the Walther Distinguished Professor in Cancer Structural Biology in the College of Science and a member of the Purdue Institute for Cancer Research. “Some of these pathways are useful, so ideally, we shouldn’t just turn off the signal at the source. But maybe we can find compounds that elicit a more nuanced response inside the cell, such as by preserving good pathways and dampening those that are bad.”

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.