Lifeboat Foundation

The immune system is an incredibly complex network that has some amazing capabilities. It can eliminate dangerous cells that may lead to cancer, and defend the body against a wide variety of pathogenic invaders. It also has the ability to remember those encounters with pathogens so if they happen again, the immune system is primed to respond more quickly and forcefully against the offender. Scientists have now learned more about how the immune system memory is created at the molecular level. The findings have been reported in Science Immunology.

When immune cells are exposed to an invader, they can recognize structures called antigens on the surface of the pathogen. In this study, the researchers compared immune cells that had never been exposed to an antigen, so-called naive cells, to immune cells that had been in contact with an antigen, known as memory cells. The investigators wanted to identify the epigenetic differences between these cell types, which are changes in DNA that can impact gene expression, such as structural shifts or chemical tags, but do not alter the sequence of the genome. Epigenetic changes might explain why memory cells can react so quickly while naive cells are comparatively slow.

Working to integrate theology, ethics and science, ISCAT Fellow and renowned author Dr. Brian Edgar discusses the future of humanity.

The immune system is one of the most complex parts of our body. It keeps us healthy by getting rid of parasites, viruses or bacteria, and by destroying damaged or cancer cells. One of its most intriguing abilities is its memory: upon first contact with a foreign component (called antigens) our adaptive immune system takes around two weeks to respond, but responses afterwards are much faster, as if the cells remembered the antigen. But how is this memory attained?

In a recent publication, a team of researchers coordinated by Dr. Ralph Stadhouders, from Erasmus MC, and Dr. Gregoire Stik, Group Leader at the Josep Carreras Leukemia Research Institute, provides new clues on immune memory using state-of-the-art methodologies.

In their research paper, published in the journal Science Immunology, the first-author Anne Onrust-van Schoonhoven and colleagues compared the response of immune cells that had never been in contact with an antigen (called naïve cells) with cells previously exposed to antigen (memory cells) and sort of knew it. They focused on the differences in the epigenetic control of the cellular machinery and the nuclear architecture of the cells, two mechanisms that could explain the quick activation pattern of memory cells.

A national study, led by researchers at Tufts Medical Center, has found whole genome sequencing (WGS) to be nearly twice as effective as a targeted gene sequencing test at identifying abnormalities responsible for genetic disorders in newborns and infants. The Genomic Medicine in Ill Infants and Newborns (GEMINI) study did, however, find that time to results was longer when carrying out WGS, when compared with a commercially available targeted neonatal gene-sequencing test.

“More than half of the babies in our study had a genetic disorder that would have remained undetected at most hospitals across the country if not for genome sequencing technologies,” said Jonathan Davis, MD, chief of newborn medicine at Tufts Medical Center and co-principal investigator of the study. “Successfully diagnosing an infant’s genetic disorder as early as possible helps ensure they receive the best medical care. This study shows that WGS, while still imperfect, remains the gold standard for accurate diagnosis of genetic disorders in newborns and infants.”

The study, “A Comparative Analysis of Rapid Whole Genomic Sequencing and a Targeted Neonatal Gene Panel in Infants with a Suspected Genetic Disorder: The Genomic Medicine for Ill Neonates and Infants (GEMINI) Study,” is reported in The Journal of the American Medical Association (J AMA).

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Connected technology tools can be stepping-stones to a new world in diverse areas such as genetic engineering, augmented reality, robotics, and renewable energies. But they need cyber protection.

Last year, the chemist – who is an emeritus professor at the University of Strasbourg – published a book titled The Elegance of Molecules. In the pages, he lets his imagination run wild. “Over time, most of the chemical reactions that govern nature could be controlled or imitated by a nanorobot: counter-offensives by the immune system, the production of antibodies, hormones on demand, the repairing of damaged cells and organs [or] the correction of anomalies in the genetic text,” Sauvage writes. “None of this will belong in the realm of science fiction in the long-term.”

Sitting in the hotel’s restaurant, however, the researcher’s realism contrasts with his futuristic fantasy. “Today, we can’t do much. Molecular machines are a somewhat new concept: we can make molecules that move as we choose [and] we can make a fairly complex molecule perform a rotary motion. Or we can make it behave like a muscle, stretching and contracting. The applications will arrive in the future, but we’re not there yet,” he stresses.

The French researcher has been developing these molecular muscles since 2002 alongside a Spanish chemist – María Consuelo Jiménez – from the Polytechnic University of Valencia. “The first thing was to show that we can make a molecule that contracts and stretches. Now, you can think of making materials – especially fibers – that can contract and stretch. Perhaps artificial muscles could be made to replace damaged muscles in people, but that will be in the future. At the moment, there are no real applications,” Sauvage clarifies.

Researchers developed a new method called wildDISCO that uses standard antibodies to map the entire body of an animal using fluorescent markers. This revolutionary technique provides detailed 3D maps of structures, shedding new light on complex biological systems and diseases. WildDISCO has the potential to transform our understanding of intricate processes in health and disease and paves the way for exciting advancements in medical research. This technology was now introduced in Nature Biotechnology.

In the past, scientists relied on genetically modified animals or specialized labels to make specific structures and cells of interest visible in the entire body of an animal. But these approaches are expensive and time-consuming to create, especially when it comes to body-wide systems such as the nervous system.

A team of scientists from Helmholtz Munich, the LMU University Hospital and the Ludwig-Maximilians Universität München (LMU) now introduced a new method called wildDISCO, which makes use of standard antibodies to map whole bodies of mice. This ultimately enables the creation of detailed three-dimensional maps of normal and diseased structures in mammalian bodies in an easy-to-use and cost-efficient way.

With triplex origami, scientists can achieve a level of artificial control over the shape of double-stranded DNA that was previously unimaginable, thereby opening new avenues of exploration, according to the Aarhus University researchers. It has recently been suggested that triplex formation plays a role in the natural compaction of genetic DNA and the current study may offer insight into this fundamental biological process.

Potential in gene therapy and beyond

The work also demonstrates that the Hoogsteen-mediated triplex formation shields the DNA against enzymatic degradation. Thus, the ability to compact and protect DNA with the triplex origami method may have large implications for gene therapy, wherein diseased cells are repaired by encoding a function that they are missing into a deliverable piece of double-stranded DNA.

Genomic analyses, such as next-generation sequencing (NGS) and quantitative polymerase chain reaction (qPCR), require pure nucleic acids and accurate analyte concentrations to perform successful reactions. The purification process to access this genetic material uses methods that rely on detergents, mechanical disruption, and heat to disrupt the cellular structures of nuclei, ribosomes, bacteria, and viruses. Nucleic acid is then purified by performing a solvent extraction, alcohol precipitation, and salting-out.

Contaminants can copurify with nucleic acids

Isolation of nucleic acids (including various forms of DNA and RNA) may be needed from cell harvest, PCR, restriction enzyme digest, agarose gel, and other sources. Several avenues in nucleic acid extraction protocols inadvertently allow the co-precipitation of contaminants owing to the type of starting material or the chosen extraction method (Table 1). In some cases, changing the method or adding another purification step can mitigate or eliminate the copurification issue. However, when contamination remains an issue, it is important to learn as much as possible about the impurities that can denature enzymes, block templates, or otherwise lead to failed chemical reactions necessary for downstream applications.