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.

Purdue researchers create biocompatible nanoparticles to enhance systemic delivery of cancer immunotherapy

Purdue University researchers are developing and validating patent-pending nanoparticles (left) to enhance immunotherapy effects against tumors. The nanoparticles are modified with adenosine triphosphate, or ATP, to recruit dendritic cells (right), which are immune cells that recognize tumor antigens and bring specialized immune cells to fight off tumors.
Image Credit: Yoon Yeo

Purdue University researchers are developing and validating patent-pending poly (lactic-co-glycolic acid), or PLGA, nanoparticles modified with adenosine triphosphate, or ATP, to enhance immunotherapy effects against malignant tumors.

The nanoparticles slowly release drugs that induce immunogenic cell death, or ICD, in tumors. ICD generates tumor antigens and other molecules to bring immune cells to a tumor’s microenvironment. The researchers have attached ATP to the nanoparticles, which also recruits immune cells to the tumor to initiate anti-tumor immune responses. 

Yoon Yeo leads a team of researchers from the College of Pharmacy, the Metabolite Profiling Facility in the Bindley Bioscience Center, and the Purdue Institute for Cancer Research to develop the nanoparticles. Yeo is the associate department head and Lillian Barboul Thomas Professor of Industrial and Molecular Pharmaceutics and Biomedical Engineering; she is also a member of the Purdue Institute for Drug Discovery and the Purdue Institute for Cancer Research.

The researchers validated their work using paclitaxel, a chemotherapy drug used to treat several types of cancers. They found that tumors grew slower in mice treated with paclitaxel enclosed within ATP-modified nanoparticles than in mice treated with paclitaxel in non-modified nanoparticles.

“When combined with an existing immunotherapy drug, the ATP-modified, paclitaxel-loaded nanoparticles eliminated tumors in mice and protected them from rechallenge with tumor cells,” Yeo said.

Rice study identifies protein responsible for gas vesicle clustering in bacteria

Zongru Li (left) and George Lu
Photo Credit: Anna Stafford/Rice University

Gas vesicles are hollow structures made of protein found in the cells of certain microorganisms, and researchers at Rice University believe they can be programmed for use in biomedical applications.

“Inside cells, gas vesicles are packed in a beautiful honeycomb pattern. How this pattern is formed has never been thoroughly understood. We are presenting the first identification of a protein that can regulate this patterning, and we believe this will be a milestone in molecular microbiology,” said George Lu, assistant professor of bioengineering and a Cancer Prevention and Research Institute of Texas scholar.

Lu and colleagues have published their findings in a paper published in Nature Microbiology. The lead author is Zongru Li, a fourth-year bioengineering doctoral student in Lu’s Laboratory for Synthetic Macromolecular Assemblies.

“Gas vesicles are cylindrical tubes closed by conical end caps,” Li said. “They provide buoyancy within the cells of their native hosts.”

Blood analysis predicts sepsis and organ failure in children

Photo Credit: Edward Jenner

University of Queensland researchers have developed a method to predict if a child is likely to develop sepsis and go into organ failure.

Associate Professor Lachlan Coin from UQ’s Institute for Molecular Bioscience said sepsis was a life-threatening condition where a severe immune response to infection causes organ damage.

“Our research involved more than 900 critically ill children in the emergency departments and intensive care units of four Queensland hospitals,” Dr Coin said.

“Blood samples were taken from these patients at the acute stage of their infection, and we analyzed which genes were activated or deactivated.

“We were able to identify patterns of gene expression which could predict whether the child would develop organ failure within the next 24 hours, as well as whether the child had a bacterial or viral infection or a non-infectious inflammatory syndrome.”

Professor Luregn Schlapbach from UQ’s Child Health Research Centre said sepsis is best treated when recognized early, so the finding could help clinicians in the future.

Messenger RNAs with multiple “tails” could lead to more effective therapeutics

Graphic showing scientists adding "tails" to mRNA molecules
Illustration Credit: Catherine Boush, Broad Communications

Messenger RNA (mRNA) made its big leap into the public limelight during the pandemic, thanks to its cornerstone role in several COVID-19 vaccines. But mRNAs, which are genetic sequences that instruct the body to produce proteins, are also being developed as a new class of drugs. For mRNAs to have broad therapeutic uses, however, the molecules will need to last longer in the body than those that make up the COVID vaccines. 

Researchers from the Broad Institute of MIT and Harvard and MIT have engineered a new mRNA structure by adding multiple “tails” to the molecules that boosted mRNA activity levels in cells by 5 to 20 times. The team also showed that their multi-tailed mRNAs lasted 2 to 3 times longer in animals compared to unmodified mRNA, and when incorporated into a CRISPR gene-editing system, resulted in more efficient gene editing in mice. 

The new mRNAs, reported in Nature Biotechnology, could potentially be used to treat diseases that require long-lasting treatments that edit genes or replace faulty proteins. 

“The use of mRNA in COVID vaccines is fantastic, which prompted us to explore how we could expand the possible therapeutic applications for mRNA,” said Xiao Wang, senior author of the new paper, a core institute member at the Broad and an assistant professor of chemistry at MIT. “We’ve shown that non-natural structures can function so much better than naturally occurring ones. This research has given us a lot of confidence in our ability to modify mRNA molecules chemically and topologically.”