The scientific community has made significant strides in recent years towards developing innovative methods for producing and analyzing complex molecules. In an exciting breakthrough, researchers from Ca’ Foscari University of Venice, along with international collaborators, have successfully harnessed the potential of brewer’s yeast to create miniature factories that produce macrocyclic peptides – promising drugs with high therapeutic value.

Macrocyclic peptides are a class of molecules that offer precision targeting, stability, and safety, making them an attractive alternative to traditional drugs. However, conventional methods for discovering and testing these peptides have been complex, slow, and environmentally unfriendly. To overcome these limitations, the researchers engineered brewer’s yeast cells to individually produce different macrocyclic peptides.

Each yeast cell acts as a tiny factory that lights up when producing the compound, allowing scientists to swiftly identify promising peptides. Using advanced fluorescence-based techniques, the team screened billions of micro-factories in just a few hours – a process significantly faster and more ecofriendly than existing methods.

Lead author Sara Linciano explained the innovative approach: “We manipulated yeast cells so that each one functions as a ‘micro-factory’ that becomes fluorescent when producing a specific compound. This allowed us to analyze 100 million different peptides rapidly and effectively.”

The study’s co-leader, Ylenia Mazzocato, highlighted the sustainability of their approach: “By exploiting the natural machinery of yeast, we produce peptide molecules that are biocompatible and biodegradable, making them safe for health and the environment – a truly ‘green pharma’ approach.”

The researchers also demonstrated the excellent binding properties of these peptides using X-ray crystallography. This new method offers significant advancements for drug discovery, especially for challenging targets that conventional drugs cannot easily address.

As Alessandro Angelini, associate professor and study coordinator, emphasized: “We are pushing the boundaries of this technology to create macrocyclic peptides that can deliver advanced therapies directly to specific cells, potentially revolutionising treatments. This could greatly benefit patient health and have substantial scientific and economic impacts.”

This work was part of the National Recovery and Resilience Plan (PNRR), supported by the European Union’s Next Generation EU initiative. The team involved multidisciplinary experts from Ca’ Foscari University of Venice, Kyoto Institute of Technology, Chinese Academy of Sciences, University of Padova, and École Polytechnique Fédérale de Lausanne.

Part of this technology has already been patented by Ca’ Foscari and was recently acquired by the startup Arzanya S.r.l. As Angelini concluded: “Seeing our technology gain international recognition makes me proud. I hope Arzanya S.r.l. can provide our talented young researchers with the opportunity to pursue their passions here in Italy, without necessarily needing to move abroad.”

The COVID-19 pandemic has taken a devastating toll on global health, with severe complications and immune-driven tissue damage being major concerns. A recent study published in Cell Reports reveals that the SARS-CoV-2 nucleocapsid protein can spread from infected to uninfected cells, triggering an immune response that mistakenly targets healthy cells. Researchers at the Hebrew University of Jerusalem have identified how this viral protein binds to cell surfaces and found a common anticoagulant, enoxaparin, can block this harmful interaction.

The study, led by PhD students Jamal Fahoum and Maria Billan from the Faculty of Medicine at the Hebrew University of Jerusalem, uncovers a surprising mechanism by which the SARS-CoV-2 virus causes immune-mediated tissue damage. The researchers used laboratory-grown cells, sophisticated imaging techniques, and samples from COVID-19 patients to understand how a specific viral protein attaches to healthy cells.

They discovered that this protein sticks to certain sugar-like molecules found on the surface of many cells, called Heparan Sulfate proteoglycans. When this happens, clumps of the viral protein form on these healthy cells. The immune system then mistakenly attacks these clumps using antibodies, which sets off a chain reaction that might damage both infected and healthy cells in the infected organism.

However, the researchers found that the drug enoxaparin can block the viral protein from sticking to healthy cells by taking over the spots the protein would normally bind to. In both lab experiments and when samples obtained from patients were tested in the lab, enoxaparin stopped the protein from attaching to cells and helped prevent the immune system from mistakenly attacking them.

This research sheds light on the mechanisms behind severe COVID-19 complications and immune-driven tissue damage. The findings open the door to new strategies for preventing immune-driven damage in COVID-19 and possibly other viral infections. Moreover, this study highlights the importance of collaborative efforts between clinicians and researchers in understanding the complexities of viral infections.

The authors dedicate this article to the memory of the late Prof. Hervé (Hillel) Bercovier, a gifted microbiologist, an inspiring scientist, and a great mentor. This research was supported by several research funds, including major contributions from The Edmond and Benjamin de Rothschild Foundation and The Israel Science Foundation of the Israel Academy of Science and Humanities.

Scientists at the USC Leonard Davis School of Gerontology have made a groundbreaking discovery that sheds light on the unique challenges faced by people with Down syndrome who develop Alzheimer’s disease. Their research reveals a crucial link between high levels of iron in the brain and increased cell damage, providing a potential explanation for why Alzheimer’s symptoms often appear earlier and more severely in individuals with Down syndrome.

Down syndrome is caused by having an extra third copy (trisomy) of chromosome 21, which includes the gene for amyloid precursor protein (APP). People with Down syndrome tend to produce more APP, leading to an increased risk of developing Alzheimer’s disease. In fact, about half of all people with Down syndrome show signs of Alzheimer’s by the age of 60, which is approximately 20 years earlier than in the general population.

The researchers studied donated brain tissue from individuals with Alzheimer’s, those with both Down syndrome and Alzheimer’s (DSAD), and those without either diagnosis. They found that the brains of people with DSAD had twice as much iron and more signs of oxidative damage in cell membranes compared to the brains of individuals with Alzheimer’s alone or those with neither diagnosis.

This excess iron leads to ferroptosis, a type of cell death characterized by iron-dependent lipid peroxidation. In other words, iron builds up, drives the oxidation that damages cell membranes, and overwhelms the cell’s ability to protect itself.

The researchers also discovered that lipid rafts, tiny parts of the brain cell membrane crucial for cell signaling and protein processing, had more oxidative damage and fewer protective enzymes in DSAD brains compared to Alzheimer’s or healthy brains. These lipid rafts showed increased activity of the enzyme β-secretase, which interacts with APP to produce Aβ proteins, potentially promoting the growth of amyloid plaques.

The findings have significant implications for future treatments, especially for people with Down syndrome who are at high risk of Alzheimer’s. Early research in mice suggests that iron-chelating treatments may reduce indicators of Alzheimer’s pathology. Medications that remove iron from the brain or help strengthen antioxidant systems might offer new hope.

The study was supported by various organizations, including the National Institute on Aging and Cure Alzheimer’s Fund. These findings highlight the importance of understanding the biology of Down syndrome for Alzheimer’s research and could lead to new therapeutic approaches for this vulnerable population.