How chromosomes separate accurately

Representation how separase recognizes the cohesin subunit SCC1 before chromosome segregation occurs.
Illustration Credit: © Margot Riggi

Cell division is a process of remarkable precision: during each cycle, the genetic material must be evenly distributed between the two daughter cells. To achieve this, duplicated chromosomes, known as sister chromatids, are temporarily linked by cohesin – a ring-shaped protein complex that holds them together until separation. Researchers at the University of Geneva (UNIGE), in collaboration with the National Cancer Institute (NCI) and the University of California, San Francisco (UCSF), have uncovered the mechanism by which separase – the molecular ‘‘scissors’’ responsible for this cleavage – recognizes and cuts cohesin. Their findings, published in Science Advances, shed new light on chromosome segregation errors that can lead to certain forms of cancer. 

Thyroid gland new possible target for prostate cancer treatment

Lukas Kenner, visiting professor at the Department of Molecular Biology.
Photo Credit: Medizinische Universität Wien

A hormone produced in the thyroid gland can play a key role in the development of prostate cancer. This is shown in a new study by an international research group led by Umeå University, Sweden, and the Medical University of Vienna, Austria. By blocking a receptor for the hormone, the growth of tumor cells in the prostate was inhibited. In the long term, the discovery may open up a new way of attacking certain types of aggressive prostate cancer.

"The results indicate that the receptor in question is a driving force in the growth of cancer. Substances that block it could thus be a target for future drugs against prostate cancer," says Lukas Kenner, visiting professor at Umeå University and the one who has led the study that is published in Molecular Cancer.

The receptor in question is called thyroid hormone receptor Beta, TRβ. It binds the thyroid hormone triiodothyronine, T3. In laboratory experiments, the activation of T3 has led to a sharp increase in the number of prostate cancer cells. However, when the receptor TRβ was inhibited with the help of an active substance, NH-3, significantly reduced the growth of cancer cells. NH-3 is a substance that is only used in research to block TRβ.

Scientists Removed Amino Acids From the Diet of Lab Mice — and They Lost Weight

Legumes are a diverse group of plants from the Fabaceae family, including beans, peas, lentils, and peanuts, that grow in pods. They are a highly nutritious food, rich in protein, fiber, vitamins, and minerals, and are often considered a plant-based alternative to animal protein. Legumes also have the unique ability to fix nitrogen from the atmosphere, which benefits soil health.
Photo Credit: Shelley Pauls

It’s not pleasant to shiver from the cold, but for some, it has the appeal of making the body burn more energy as heat than when staying in a warmer environment. According to several studies, exposure to cold is a reliable way to boost energy expenditure in mice and humans. This process of burning energy through heat loss is called thermogenesis.

While scientists and pharmaceutical companies are exploring ways to trick the body into thinking it’s cold—so that it activates thermogenesis and burns energy without the need for ice baths or winter walks in a T-shirt—obesity researchers Philip Ruppert and Jan-Wilhelm Kornfeld from the Department of Biochemistry and Molecular Biology (BMB) set out to investigate another route:

A form of thermogenesis triggered by eating specialized diets rather than temperature.

What Is: Hormones

The "Chemical Messenger"
The Endocrine System and Chemical Communication
Image Credit: Scientific Frontline

The Silent Orchestrators

Hormones are the silent orchestrators of the human body. They are the unseen chemical messengers that, in infinitesimally small quantities, conduct the complex symphony of life. These powerful molecules control and regulate nearly every critical function, from our mood, sleep, and metabolism to our growth, energy levels, and reproductive functions.

At its most fundamental level, a hormone is a chemical substance produced by a gland, organ, or specialized tissue in one part of the body. It is then released—typically into the bloodstream—to travel to other parts of the body, where it acts on specific "target cells" to coordinate function.

The power of this system, which has identified over 50 distinct hormones in humans, lies in its exquisite specificity. Although hormones circulate throughout the entire body, reaching every cell, they only affect the cells that are equipped to listen. This is governed by the "lock and key" principle: target cells possess specific "receptors," either on their surface or inside the cell, that are shaped to bind only to a compatible hormone. This report will delve into the world of these powerful molecules, exploring the intricate system that creates them, the chemical language they speak, and the profound, lifelong impact they have on our daily health and well-being.

OHSU researchers develop promising drug for aggressive breast cancer

New research reveals a drug developed by scientists at Oregon Health & Science University may develop into a new treatment for an especially aggressive form of breast cancer.
Photo Credit: Oregon Health & Science University

A new molecule developed by researchers at Oregon Health & Science University offers a promising avenue to treat intractable cases of triple-negative breast cancer — a form of cancer that is notoriously aggressive and lacks effective treatments.

In a study published today in the journal Cell Reports Medicine, researchers describe the effect of a molecule known as SU212 to inhibit an enzyme that is critical to cancer progression. The research was conducted in a humanized mouse model.

“It’s an important step forward to treat triple-negative breast cancer,” said senior author Sanjay V. Malhotra, Ph.D., co-director of the Center for Experimental Therapeutics in the OHSU Knight Cancer Institute. “Triple-negative breast cancer is an aggressive form of cancer and there are no effective drugs available right now.”

Researchers decipher mechanism that prevents the loss of brown adipose tissue activity during ageing

From left to right, Tania Quesada-López, Francesc Villarroya, Albert Blasco-Roset, Marta Giralt, Alberto Mestres-Arenas, Joan Villarroya, Aleix Gavaldà-Navarro and Rubén Cereijo.
Photo Credit: Courtesy of University of Barcelona

As the body ages, brown adipose tissue activity decreases, fewer calories are burned, and this can contribute to obesity and certain chronic cardiovascular diseases that worsen with age. A study led by the University of Barcelona has identified a key molecular mechanism in the loss of brown fat activity during ageing. The study opens up new perspectives for designing strategies to boost the activity of this tissue and prevent chronic metabolic and cardiovascular diseases as the population ages.

The paper, published in the journal Science Advances, is led by Professor Joan Villarroya, from the Faculty of Biology and the Institute of Biomedicine of the UB (IBUB) — based at the Barcelona Science Park-UB  — and the CIBER Area for Physiopathology of Obesity and Nutrition  (CIBEROBN). Teams from the Albert Einstein College of Medicine in New York (United States) are also collaborating.

Researchers decipher a mechanism that determines the complexity of the glucocorticoid receptor

Above, from left to right, Pilar Montanyà-Vallugera, José Luis Torbado-Gardeazábal, Inés Montoya-Novoa and Montse Abella-Monleón. Below, from left to right, Alba Jiménez-Panizo, Pablo Fuentes-Prior, Eva Estébanez-Perpiñá and Andrea Alegre-Martí.
Photo Credit: Courtesy of University of Barcelona

Drugs to treat inflammatory and autoimmune diseases — such as asthma, psoriasis, rheumatoid arthritis or Chrousos syndrome — act mainly through the glucocorticoid receptor (GR). This essential protein regulates vital processes in various tissues, so understanding its structure and function at the molecular level is essential for designing more effective and safer drugs. Now, a study published in the journal Nucleic Acids Research (NAR) has revealed the mechanism of multimerization — the association of different molecules to form complex structures — of the glucocorticoid receptor, a process critical to its physiological function.

Deciphering how the GR forms oligomers — through the binding of several subunits — opens a crucial avenue for developing more selective drugs. These new drugs could modulate this association and thus minimize serious adverse effects, such as immunosuppression or bone loss.

In a surprising discovery, scientists find tiny loops in the genomes of dividing cells

MIT experiments have revealed the existence of “microcompartments,” shown in yellow, within the 3D structure of the genome. These compartments are formed by tiny loops that may play a role in gene regulation.
Illustration Credit: Ed Banigan, edited by MIT News
(CC BY-NC-ND 4.0)

Before cells can divide, they first need to replicate all of their chromosomes, so that each of the daughter cells can receive a full set of genetic material. Until now, scientists had believed that as division occurs, the genome loses the distinctive 3D internal structure that it typically forms.

Once division is complete, it was thought, the genome gradually regains that complex, globular structure, which plays an essential role in controlling which genes are turned on in a given cell.

However, a new study from MIT shows that in fact, this picture is not fully accurate. Using a higher-resolution genome mapping technique, the research team discovered that small 3D loops connecting regulatory elements and genes persist in the genome during cell division, or mitosis.

“This study really helps to clarify how we should think about mitosis. In the past, mitosis was thought of as a blank slate, with no transcription and no structure related to gene activity. And we now know that that’s not quite the case,” says Anders Sejr Hansen, an associate professor of biological engineering at MIT. “What we see is that there’s always structure. It never goes away.”

The Many FACES of Lipid Research

Subcellular lipid distributions (magenta) in mitochondria (green) revealed using FACES and super-resolution structure illuminated microscopy.
Image Credit: William Moore

Lipids are fatty molecules that play critical roles in cell function, including membrane structure, energy storage and nutrient absorption. Most lipids are made in a cell organelle called the endoplasmic reticulum, but specific lipid types are shuttled around to different parts of the cell depending on their purpose. Each organelle serves a specific role in a cell and has its own unique mixture of lipids called a lipidome.

Scientists have long wanted to get a closer look at the movement of lipids around a cell, but because organelles are so close together – often only tens of nanometers apart – it’s tough to visualize with traditional light microscopy, which only has resolutions up to 250 nanometers.

Now researchers at the University of California San Diego have unveiled a new technology with the power to see cells in unprecedented detail. The tool, called fluorogen-activating coincidence encounter sensing (FACES), was developed in Associate Professor of Biochemistry & Molecular Biophysics Itay Budin’s lab. This work appears in Nature Chemical Biology.

“Molecular bodyguard” helps infections persist

Joram Waititu and Kemal Avican working together in the Avican Lab at the Department of Molecular Biology, Umeå University.
Photo Credit: Gabrielle Beans

Researchers at Umeå University have identified a key molecular player that helps bacteria survive the hostile environment inside the body. Their study reveals how the protein RfaH acts as a protective shield for bacterial genes — and points to new strategies for fighting persistent infections.

“The human body is a very stressful place for bacteria,” says Kemal Avican research group leader at Department of Molecular Biology and Icelab at Umeå University and leader of the study. “During infection, the immune system attacks, nutrients are scarce, and microbes are exposed to bile salts, acids and heat. We looked at how RfaH helps bacteria deal with that stress by turning on the right survival genes at the right time.”

Persistent bacterial infections pose a major challenge in medicine: bacteria can linger in the body long after acute symptoms fade, evading immune defenses and surviving antibiotic treatment. In diseases like tuberculosis, this leads to relapse and makes treatment difficult.

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.