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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.

Scientists at Leipzig University, in collaboration with colleagues at Vilnius University in Lithuania, have developed a new method to measure the smallest twists and torques of molecules within milliseconds. The method makes it possible to track the gene recognition of CRISPR-Cas protein complexes, also known as “genetic scissors”, in real time and with the highest resolution. With the data obtained, the recognition process can be accurately characterised and modelled to improve the precision of the genetic scissors. The results obtained by the team led by Professor Ralf Seidel and Dominik Kauert from the Faculty of Physics and Earth Sciences have now been published in the prestigious journal Nature Structural and Molecular Biology.

When bacteria are attacked by a virus, they can defend themselves with a mechanism that fends off the genetic material introduced by the intruder. The key is CRISPR-Cas protein complexes. It is only in the last decade that their function for adaptive immunity in microorganisms has been discovered and elucidated. With the help of an embedded RNA, the CRISPR complexes recognize a short sequence in the attacker’s DNA. The mechanism of sequence recognition by RNA has since been used to selectively switch off and modify genes in any organism. This discovery revolutionized genetic engineering and was already honored in 2020 with the Nobel Prize in Chemistry awarded to Emmanuelle Charpentier and Jennifer A. Doudna.

Occasionally, however, CRISPR complexes also react to gene segments that differ slightly from the sequence specified by the RNA. This leads to undesirable side effects in medical applications. “The causes of this are not yet well understood, as the process could not be observed directly until now,” says Dominik Kauert, who worked on the project as a PhD student.

A cell’s identity is based on the genes it expresses, and scientists have been studying gene expression mechanisms for many years. But the process involves molecules that are too small to see, until the recent development of a technique called expansion microscopy. With expansion microscopy, scientists preserve tissue, and then enlarge it; this can make very small structures much easier to see. Researchers have now improved the technology, and even after increasing the size of zebrafish embryonic cell nuclei by 4,000 times, they were able to see the influence of individual molecules on gene expression. The findings, which have enhanced our understanding of gene regulation, have been reported in Science.

With this technique, investigators can now visualize the fundamental processes of the cell that form the basis of life. “We can see processes that we could only imagine before,” said co-senior study author Antonio Giraldez, Ph.D., Fergus F. Wallace Professor of Genetics at Yale School of Medicine.

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Research on mu heavy chain knockout mice (MuMt^-; B^null), which are mice that are genetically incapable of producing mature B-cells, has suggested that B-cells amplify the metabolic effects of diseases, especially diabetes and insulin resistance. Since type 2 diabetes (T2D) and hyperthyroidism, both of which are autoimmune conditions, are strongly correlated with PCOS, scientists have attempted to investigate an autoimmune trigger for PCOS, which has remained unsuccessful.

Study findings

In the present study, researchers evaluate previously hypothesized factors associated with cyst formation and inflammation, which include B-cell frequency, hyperandrogenemia, and autoantibodies.

Scientists discovered that a synthetic cell with a reduced genome could evolve as quickly as a normal cell. Despite losing 45% of its original genes, the cell adapted and demonstrated resilience in a laboratory experiment lasting 300 days, effectively showcasing that evolution occurs even under perceived limitations.

“Listen, if there’s one thing the history of evolution has taught us is that life will not be contained. Life breaks free. It expands to new territories, and it crashes through barriers painfully, maybe even dangerously, but… ife finds a way,” said Ian Malcolm, Jeff Goldblum’s character in Jurassic.

The Jurassic period is a geologic time period and system that spanned 56 million years from the end of the Triassic Period about 201.3 million years ago to the beginning of the Cretaceous Period 145 million years ago. It constitutes the middle period of the Mesozoic Era and is divided into three epochs: Early, Middle, and Late. The name “Jurassic” was given to the period by geologists in the early 19th century based on the rock formations found in the Jura Mountains, which were formed during the Jurassic period.

A genetic editing system similar to CRISPR-Cas9 has been uncovered for the first time in eukaryotes – the group of organisms that include fungi, plants, and animals. The system, based on a protein called Fanzor, can be guided to precisely target and edit sections of DNA, and that could open up the possibility of its use as a human genome editing tool.

The research team, led by Professor Feng Zhang at the McGovern Institute for Brain Research at MIT and the Broad Institute of MIT and Harvard, began to suspect that Fanzor proteins might act as nucleases – enzymes that can chop up nucleic acids, like DNA – during a previous investigation.

Continue reading “Newfound CRISPR-Like System In Animals Could Be Used To Manipulate Human Genomes” »

Plants have the unique ability to regenerate entirely from a somatic cell, i.e., an ordinary cell that does not typically participate in reproduction. This process involves the de novo (or new) formation of a shoot apical meristem (SAM) that gives rise to lateral organs, which are key for the plant’s reconstruction.

At the cellular level, SAM formation is tightly regulated by either positive or negative regulators (genes/protein molecules) that may induce or restrict shoot regeneration, respectively. But which molecules are involved? Are there other regulatory layers that are yet to be uncovered?

To seek answers to the above questions, a research group led by Nara Institute of Science and Technology (NAIST), Japan studied the process in Arabidopsis, a plant commonly used in genetic research. Their research—which was published in Science Advances —identified and characterized a key negative regulator of shoot regeneration.