Technique for tracking resistant cancer cells could lead to new treatments for relapsing breast cancer patients

Breast cancer cells
Image Credit: Anne Weston - Francis Crick Institute (CC BY-NC 4.0)

Tumors are complex entities made up of many types of cells, including cancer cells and normal cells. But even within a single tumor there are a diverse range of cancer cells – and this is one reason why standard therapies fail.

When a tumor is treated with anti-cancer drugs, cancer cells that are susceptible to the drug die, the tumor shrinks and the therapy appears to be successful. But in reality, a small number of cancer cells in the tumor may be able to survive the treatment and regrow, often more persistently, causing a relapse.

In a study published in eLife, scientists from Professor Greg Hannon’s IMAXT lab at the Cancer Research UK Cambridge Institute at the University of Cambridge have developed a new technique for identifying the different types of cells in a tumor. Their method – developed in mouse tumors – allows them to track the cells during treatment, seeing which types of cells die and which survive.

The IMAXT team was previously awarded £20 million by Cancer Grand Challenges, funded by Cancer Research UK.

Developing antibiotics that target multiple-drug-resistant bacteria

The sphaerimicin analogs (SPMs) inhibit the activity of MraY, and hence the replication of bacteria, with different degrees of effectiveness. The potency of the analog increases as the IC50 decrease Illustration Credit: Takeshi Nakaya, et al. Nature Communications. December 20, 2022

Researchers have designed and synthesized analogs of a new antibiotic that is effective against multidrug-resistant bacteria, opening a new front in the fight against these infections.

Antibiotics are vital drugs in the treatment of a number of bacterial diseases. However, due to continuing overuse and misuse, the number of bacteria strains that are resistant to multiple antibiotics is increasing, affecting millions of people worldwide. The development of new antibacterial compounds that target multiple drug resistant bacteria is also an active field of research so that this growing issue can be controlled.

A team led by Professor Satoshi Ichikawa at Hokkaido University has been working on the development of new antibacterial. Their most recent research, published in the journal Nature Communications, details the development of a highly effective antibacterial compound that is effective against the most common multidrug-resistant bacteria.

Polarity proteins shape efficient “breathing” pores in grasses

One of the two “compass proteins” (POLAR, in pink) orients the future cell division. In grey there are cell outlines on the developing leaf.
Image Credit: ZVG / Courtesy of Michael T. Raissig

A research group at the University of Bern is studying how plants "breathe". They have gained new insights into how grasses develop efficient "breathing pores" on their leaves. If important landmark components in this development process are missing, the gas exchange between plant and atmosphere is impaired. The findings are also important regarding climate change.

Grasses have "respiratory pores" (called stomata) that open and close to regulate the uptake of carbon dioxide for photosynthesis on the one hand and water loss through transpiration on the other. Unlike many other plants, stomata in grasses form lateral "helper cells". Thanks to these cells, the stomata of grasses can open and close more quickly, which optimizes plant-atmosphere gas exchange and thus saves water.

Why Don’t T Cells Destroy Solid Tumors during Immunotherapy?

3-D image of a T cell experiencing cell stress: endoplasmic reticulum (green), mitochondria (purple).
 Illustration Credit: Elizabeth Hunt, Thaxton lab

Led by Jessica Thaxton, PhD, MsCR, UNC School of Medicine scientists and colleagues found that targeting key proteins that control the T cell response to stress could help researchers develop more potent cancer immunotherapies.

The great hope of cancer immunotherapy is to bolster our own immune cells in specific ways to keep cancer cells from evading our immune system. Although much progress has been made, immunotherapy does not always work well. Jessica Thaxton, PhD, MsCR, in the immunotherapy group at the UNC Lineberger Comprehensive Cancer Center, wants to know why. She thinks one reason is the stress response experienced by T cells once they infiltrate solid cancers.

The Thaxton lab’s latest work, published in the journal Cancer Research, shows in detail how the stress response in T cells can lead to their inability to curtail tumor growth. Thaxton’s group found that T cells exposed to the environment of solid cancers undergo a natural response to stress that shuts off their function, limiting T cell ability to kill tumors. By manipulating multiple proteins in the stress response pathway inside T cells, Thaxton’s team showed that it was possible to overcome the intrinsic T cell stress response to allow the immune system to thwart cancer growth.

The clever glue keeping the cell’s moving parts connected

This liquid droplet is actually made from protein molecules. It acts as a glue that keeps the microtubule attached, via moving motor proteins, to an actin cable – a process essential for cell division to proceed.
 Illustration Credit: Ella Maru Studios, Courtesy of Paul Scherrer Institute

Researchers from Paul Scherrer Institute PSI and ETH Zurich have discovered how proteins in the cell can form tiny liquid droplets that act as a smart molecular glue. Clinging to the ends of filaments called microtubules, the glue they discovered ensures the nucleus is correctly positioned for cell division. The findings, published in Nature Cell Biology, explain the long-standing mystery of how moving protein structures of the cell’s machinery are coupled together.

Couplings are critical to machines with moving parts. Rigid or flexible, whether the connection between the shafts in a motor or the joints in our body, the material properties ensure that mechanical forces are transduced as desired. Nowhere is this better optimized than in the cell, where the interactions between moving subcellular structures underpin many biological processes. Yet how nature makes this coupling has long baffled scientists.

Now researchers, investigating a coupling crucial for yeast cell division, have revealed that to do this, proteins collaborate such that they condense into a liquid droplet. The study was a collaboration between the teams of Michel Steinmetz at Paul Scherrer Institute PSI and Yves Barral at ETH Zurich, with the help of the groups of Eric Dufresne and Jörg Stelling, both at ETH Zurich.

Scientists use machine learning to gain unprecedented view of small molecules

Metabolites are extremely small – the diameter of a human hair is 100,000 nanometers, while that of a glucose molecule is approximately one nanometer.
Illustration Credit: Matti Ahlgren/Aalto University.

A new tool to identify small molecules offers benefits for diagnostics, drug discovery and fundamental research.

A new machine learning model will help scientists identify small molecules, with applications in medicine, drug discovery and environmental chemistry. Developed by researchers at Aalto University and the University of Luxembourg, the model was trained with data from dozens of laboratories to become one of the most accurate tools for identifying small molecules.

Thousands of different small molecules, known as metabolites, transport energy and transmit cellular information throughout the human body. Because they are so small, metabolites are difficult to distinguish from each other in a blood sample analysis – but identifying these molecules is important to understand how exercise, nutrition, alcohol use and metabolic disorders affect wellbeing.

Learning from habitat ‘haves’ to help save a threatened rattlesnake

The study suggests that a collection of six relatively closely situated but isolated populations of Eastern massasauga rattlesnakes in northeast Ohio could grow their numbers if strategic alterations were made to stretches of land between their home ranges.
Photo Credit: Scott Martin

Comparing the genetics and relocation patterns of habitat “haves” and “have-nots” among two populations of threatened rattlesnakes has produced a new way to use scientific landscape data to guide conservation planning that would give the “have-nots” a better chance of surviving.

The study suggests that a collection of six relatively closely situated but isolated populations of Eastern massasauga rattlesnakes in northeast Ohio could grow their numbers if strategic alterations were made to stretches of land between their home ranges. The findings contributed to the successful application for federal funding of property purchases to make some of these proposed landscape changes happen.

Reconnecting these populations could not only help restore Eastern massasaugas to unthreatened status, but establish a thriving habitat for other prey and predator species facing threats to their survival – satisfying two big-picture conservation concerns, researchers say.

“We aren’t just protecting massasaugas – we’re protecting everything else that’s there,” said H. Lisle Gibbs, professor of evolution, ecology and organismal biology at The Ohio State University and senior author of the study. “Even though we are focused on this species, protection of the habitat has all these collateral benefits.”

Daylong wastewater samples yield surprises

Rice University engineers compared wastewater “grabs” to daylong composite samples and found the grab samples were more likely to result in bias in testing for the presence of antibiotic-resistant genes.
 Illustration Credit: Stadler Research Group/Rice University

Testing the contents of a simple sample of wastewater can reveal a lot about what it carries, but fails to tell the whole story, according to Rice University engineers.

Their new study shows that composite samples taken over 24 hours at an urban wastewater plant give a much more accurate representation of the level of antibiotic-resistant genes (ARGs) in the water. According to the Centers for Disease Control and Prevention (CDC), antibiotic resistance is a global health threat responsible for millions of deaths worldwide.

In the process, the researchers discovered that while secondary wastewater treatment significantly reduces the amount of target ARG, chlorine disinfectants often used in later stages of treatment can, in some situations, have a negative impact on water released back into the environment.

The lab of Lauren Stadler at Rice’s George R. Brown School of Engineering reported seeing levels of antibiotic-resistant RNA concentrations 10 times higher in composite samples than what they see in “grabs,” snapshots collected when flow through a wastewater plant is at a minimum.

Fossil CSI: Mysterious site was ancient birthing grounds

Adult and young of the ichthyosaur species Shonisaurus popularis chase ammonoid prey 230 million years ago, in what is now Berlin-Ichthyosaur State Park, Nevada, U.S.A.
Illustration Credit: Gabriel Ugueto 

Today’s marine giants—such as blue and humpback whales—routinely make massive migrations across the ocean to breed and give birth in waters where predators are scarce, with many congregating year after year along the same stretches of coastline. Now, new research from a team of scientists—including researchers with the University of Utah (Natural History Museum of Utah and Department of Geology & Geophysics), Smithsonian Institution, Vanderbilt University, University of Nevada, Reno, University of Edinburgh, University of Texas at Austin, Vrije Universiteit Brussels, and University of Oxford—suggests that nearly 200 million years before giant whales evolved, school bus-sized marine reptiles called ichthyosaurs may have been making similar migrations to breed and give birth together in relative safety.

The findings, published today in the journal Current Biology, examine a rich fossil bed in the renowned Berlin-Ichthyosaur State Park (BISP) in Nevada’s Humboldt-Toiyabe National Forest, where many 50-foot-long ichthyosaurs (Shonisaurus popularis) lay petrified in stone. Co-authored by Randall Irmis, NHMU chief curator and curator of paleontology, and associate professor, the study offers a plausible explanation as to how at least 37 of these marine reptiles came to meet their ends in the same locality—a question that has vexed paleontologists for more than half a century.

The Donnan Potential, Revealed at Last

Staff scientist Ethan Crumlin at Berkeley Lab's Advanced Light Source.
Photo Credit: Marilyn Sargent/Berkeley Lab

The Donnan electric potential arises from an imbalance of charges at the interface of a charged membrane and a liquid, and for more than a century it has stubbornly eluded direct measurement. Many researchers have even written off such a measurement as impossible.

But that era, at last, has ended. With a tool that’s conventionally used to probe the chemical composition of materials, scientists at the Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab) recently led the first direct measurement of the Donnan potential.

“We were naïve enough to believe we could do the impossible.”

Ethan Crumlin, Berkeley Lab staff scientist, Advanced Light Source (ALS)

Crumlin and his collaborators recently reported the measurement in Nature Communications.

Such a measurement could yield new insights in many areas that focus on membranes. The Donnan potential plays a critical role in transporting ions through a cellular membrane, for example, which ties it to biological functions ranging from muscle contractions to neural signaling. Ion exchange membranes are also important in energy storage strategies and water purification technologies.