Connect with us

Biology

Unlocking the Secrets of Protein Synthesis: A New Toolbox for Characterizing Internal Ribosomal Entry Sites (IRESes)

The research field of ‘cellular IRESes’ lay dormant for decades, as there was no uniform standard of reliable methods for the clear characterization of these starting points for the ribosome-mediated control of gene expression. Researchers have now developed a toolbox as a new gold standard for this field. They hope to discover strong IRES elements that are directly relevant for synthetic biology and for application in emerging mRNA therapeutics.

Avatar photo

Published

on

The research field of cellular IRESes has long been dormant due to the lack of reliable methods for characterizing these critical starting points for ribosome-mediated control of gene expression. However, researchers at the University Hospital Bonn (UKB) and the University of Bonn, in collaboration with Stanford University, have now developed a comprehensive toolbox as a new gold standard for this field.

The ribosome, one of the oldest molecular machines in evolutionary terms, has only recently been recognized as an active regulator of gene expression at the level of protein biosynthesis. This is an essential process for cell development and function, where genetic information is converted into proteins through translation. The direct interaction of the ribosome with mRNAs is being investigated by the “Immunobiochemistry” research group led by Prof. Kathrin Leppek.

IRESes are specialized, folded sequences within an RNA strand that play a crucial role in the initiation of translation and regulation of gene expression. These elements were first described in viral genomes, where they enable viruses to hijack host ribosomes for their own protein synthesis. However, recent studies have revealed IRESes in eukaryotic cells as well.

The main challenge has been the exact and reliable characterization of these newly described IRESes, particularly from eukaryotic mRNAs. The Bonn researchers have now developed a range of versatile techniques that will enable robust characterization of IRESes in the future. These include circular RNA reporters, quantitative staining techniques of individual mRNAs in mouse embryo tissue, and determination of translation rates of individual IRES-containing mRNAs.

Such a comprehensive toolbox represents a new gold standard for the robust testing and characterization of IRESes. Strong IRES elements are directly relevant for synthetic biology and emerging mRNA therapeutics, making this research particularly exciting and promising.

Ancient Civilizations

Uncovering the Past: Archaeological Evidence of Roman Gladiators Bitten by Lions Revealed in Yorkshire

Bite marks found on a skeleton discovered in a Roman cemetery in York have revealed the first archaeological evidence of gladiatorial combat between a human and a lion.

Avatar photo

Published

on

The discovery of a skeleton in a Roman cemetery in York has provided the first archaeological evidence of gladiatorial combat between humans and lions. The bite marks found on the skeleton confirm that it was a gladiator who fought against a lion, providing a rare glimpse into the lives of these ancient fighters.

Malin Holst, a lecturer in Osteoarchaeology at the University of York, led the research team that made this groundbreaking discovery. She explained that the bite marks were likely made by a lion, which confirms that the skeletons buried at the cemetery were gladiators rather than soldiers or slaves.

“This is the final piece of evidence from work that began in 2004,” said Holst. “We have been excavating and analyzing human remains from the Roman cemetery on Driffield Terrace, and this discovery provides a unique insight into the lives of these ancient fighters.”

The skeleton was buried with two others, and overlaid with horse bones. In life, it appears to have had some issues with its spine that may have been caused by overloading to its back, inflammation of its lung and thigh, as well as malnutrition as a child, which he recovered from.

The lion bite wound — confirmed by comparing it to sample bites from a lion at a zoo — was not healed and is therefore likely to have been his cause of death. It is believed that the individual was decapitated after death, which appears to have been a ritual for some individuals in the Roman period, although the reasons for this remain unclear.

Analysis of the skeleton points towards this being a Bestarius, a gladiator role undertaken by volunteers or slaves.

The discovery has significant implications for our understanding of Roman entertainment culture. It was previously thought that gladiatorial combat only took place in major cities like Rome, but this find suggests that it was also practiced in smaller cities and towns throughout the empire.

“We often have a mental image of these combats occurring at the grand surroundings of the Colosseum in Rome,” said Holst, “but these latest findings show that these sporting events had a far reach, well beyond the centre of core Roman territories.”

York appears to have held gladiator arena events until as late as the fourth century AD. The presence of distinguished Roman leaders in York would have meant they required a lavish social life, and it is not surprising to see evidence of gladiator events, as well as such an extensive burial site for them.

The research team’s findings were published in the Journal of Science and Medical Research PLoS One, and are a collaboration between the University of York, Maynooth University, Cranfield University, Durham University, King’s College London, York Archaeology, and York Osteoarchaeology Ltd.

Continue Reading

Biochemistry

“Tailoring Gene Editing with Machine Learning: A Breakthrough in CRISPR-Cas9 Enzyme Engineering”

Genome editing has advanced at a rapid pace with promising results for treating genetic conditions — but there is always room for improvement. A new paper showcases the power of scalable protein engineering combined with machine learning to boost progress in the field of gene and cell therapy. In their study, authors developed a machine learning algorithm — known as PAMmla — that can predict the properties of about 64 million genome editing enzymes. The work could help reduce off-target effects and improve editing safety, enhance editing efficiency, and enable researchers to predict customized enzymes for new therapeutic targets.

Avatar photo

Published

on

The article “Tailoring Gene Editing with Machine Learning: A Breakthrough in CRISPR-Cas9 Enzyme Engineering” discusses how researchers from Mass General Brigham have harnessed machine learning to revolutionize the field of genome editing. By developing a machine learning algorithm called PAMmla, they’ve predicted the properties of over 64 million genome editing enzymes, significantly expanding our repertoire of effective and safe CRISPR-Cas9 enzymes.

CRISPR-Cas9 enzymes are powerful tools for editing genes, but their traditional application can have off-target effects, modifying DNA at unintended sites in the genome. The researchers’ novel approach uses machine learning to better predict and tailor these enzymes, ensuring greater specificity and accuracy in gene editing. This scalable solution has the potential to transform our understanding of genetic conditions and unlock new therapeutic targets.

The study showcases the power of PAMmla by demonstrating its utility in precise editing disease-causing sequences in primary human cells and mice. The researchers have also made a web tool available for others to use this model, enabling the community to create customized enzymes tailored for specific research and therapeutic applications.

Ben Kleinstiver, PhD, and Rachel A. Silverstein, PhD candidate, are leading authors on this study, highlighting the potential of machine learning in expanding our capabilities in gene editing. This breakthrough has significant implications for the field, offering a new era of precision and safety in genome editing technology.

Continue Reading

Biology

Unlocking the Secrets of Corn Genetics: New Discoveries Could Boost Crop Productivity and Resilience

By analyzing DNA from different cells in nearly 200 lines of maize plants, research has revealed insights that could help growers better adapt their crops to a fast-changing environment.

Avatar photo

Published

on

The discovery of new insights into corn genetics could revolutionize the way we grow crops, making them more productive and resilient in the face of a changing environment. A recent study, led by researchers at the University of Michigan, has shed light on how different cells within maize plants use genes to influence their physical traits.

According to Alexandre Marand, assistant professor of molecular, cellular and developmental biology, “most phenotypic variation comes from changes to regulation of a gene: when the gene is expressed, where it’s expressed and how much of it is expressed.” This means that subtle differences in gene regulation can have significant effects on the physical characteristics of plants.

For years, scientists have been able to sequence corn’s full genome and spot even slight genetic variations between specimens. However, these molecular-level differences often didn’t account for the large-scale differences that matter most to farmers.

The researchers began to suspect that how different cells used genes could play a crucial role in this disconnect. Although every cell in an organism shares the same genes, different cells use those genes differently.

Marand and his team’s latest study, published in the journal Science, has taken significant steps towards bridging this gap. By analyzing DNA from different cells in nearly 200 lines of maize plants, they revealed previously hidden information about gene activity inside various cell types.

“This really helps with prediction,” Marand said. “It lets us ask beforehand, ‘if we make changes, are they going to be additive or even synergistic?’ Will it be one plus one equals two? Or maybe it’s 10 — or negative 20.'”

The work also provides a head start in understanding where the best opportunities for synergy are waiting. Corn originated in tropical regions and has evolved into varieties that can now tolerate temperate climes.

By studying so many different varieties of corn, the new study shed light on evolutionary changes, helping understand how maize changed as growers selected the best performing plants in their environment.

“We can use that information to continue to improve plants and to make corn more adaptable to different climates,” Marand said. The researchers at the University of Georgia and the University of Munich also contributed to the study, which was supported by the National Institutes of Health, the National Science Foundation, and the University of Georgia Office of Research.

This breakthrough has significant implications for agriculture, allowing farmers to optimize crop growth and increase productivity in response to environmental changes. It’s a testament to the power of scientific research and collaboration to drive innovation and improve the world around us.

Continue Reading

Trending