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Summary: Blood tests revealed specific epigenetic biomarkers for schizophrenia. Researchers applied machine learning to analyze the CoRSIVs region of the human genome to identify the schizophrenia biomarkers. Testing the model with an independent data set revealed the AI technology can detect schizophrenia with 80% accuracy.

Source: Baylor College of Medicine.

An innovative strategy that analyzes a region of the genome offers the possibility of early diagnosis of schizophrenia, reports a team led by researchers at Baylor College of Medicine. The strategy applied a machine learning algorithm called SPLS-DA to analyze specific regions of the human genome called CoRSIVs, hoping to reveal epigenetic markers for the condition.

Using a technique called optogenetics, researchers added light-sensitive proteins to the man’s retina, giving him a blurry view of objects.

When the Human Genome Project reached its ambitious goal of mapping the entire human genome, it seemed the world was entering an era of personalized medicine, where evidence from our own specific genetic material would guide our care.

That was 2003, and nearly a generation after that spectacular collaborative achievement, we are still waiting for that promise to materialize. We may know that a person carries a gene associated with breast cancer, for example, but not whether that person will go on to develop the disease.

New research by McMaster University evolutionary biologist Rama Singh suggests the reason is that there is another, hidden layer that controls how genes interact, and how the many billions of possible combinations produce certain results. That layer is composed of largely uncharted biochemical pathways that control gene expression in cells through chemical reactions.

Modified RNA CRISPR boosts gene knockdown in human cells.

In the latest of ongoing efforts to expand technologies for modifying genes and their expression, researchers in the lab of Neville Sanjana, PhD, at the New York Genome Center (NYGC) and New York University (NYU) have developed chemically modified guide RNAs for a CRISPR system that targets RNA instead of DNA. These chemically-modified guide RNAs significantly enhance the ability to target – trace, edit, and/or knockdown – RNA in human cells.

Longevity. Technology: In the study published in Cell Chemical Biology, the research team explores a range of different RNA modifications and details how the modified guides increase efficiencies of CRISPR activity from 2-to 5-fold over unmodified guides. They also show that the optimised chemical modifications extend CRISPR targeting activity from 48 hours to four days.

Continue reading “RNA CRISPR gene editing boosts gene knockdown in human cells” »

From the time of Aristotle, it has been known that the human liver has the greatest regenerative capacity of any organ in the body, being able to regrow even from a 70% amputation, which has enabled live-donor transplants. Although the liver regenerates fully upon injury, the mechanisms that regulate how to activate or stop the process and when regeneration is terminated, are still unknown. Researchers at the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) in Dresden (Germany), at the Gurdon Institute (Cambridge, UK) and at the University of Cambridge (Biochemistry Department) have now found that a regulatory cell type—mesenchymal cell—can activate or stop liver regeneration. The mesenchymal cells do so by the number of contacts they establish with the regenerating cells (epithelial cells). This study suggests that mistakes in the regeneration process, which can give rise to cancer or chronic liver diseases, are caused by the wrong number of contacts between both populations. The work is described in a paper published in the journal Cell Stem Cell on 2nd August 2021.

The molecular mechanisms by which adult liver cells trigger the regenerative response remain largely unknown. Approximately 29 million people in Europe suffer from a chronic liver condition such as cirrhosis or liver cancer. They are a major cause of morbidity and mortality with liver diseases accounting for approximately two million deaths per year worldwide. Currently, there is no cure and liver transplants are the only treatment for liver failure. Scientists are therefore exploring new options for how to trigger the regenerative capacity of the liver as an alternative means to restore function.

Although visible signs of aging are usually unmistakable, unraveling what triggers them has been quite a challenge. Researchers at Baylor College of Medicine and collaborating institutions have discovered that a cellular phenomenon called cryptic transcription, which had been previously described and linked to aging in yeasts and worms, is elevated in aging mammalian stem cells.

The team reports in the journal Nature Aging that cryptic transcription occurs because a cellular mechanism that keeps it in check falls apart as cells get old. The findings suggest that strategies that control cryptic transcription could have pro-longevity effects.

“In previous work, we showed that cryptic transcription in yeasts and worms is not only a marker of aging but also a cause,” said corresponding author Dr. Weiwei Dang, assistant professor of molecular and human genetics and the Huffington Center on Aging at Baylor. “Reducing the amount of this aberrant transcription in these organisms prolonged their lifespan.”

A new discovery explains what determines the number and position of genetic exchanges that occur in sex cells, such as pollen and eggs in plants, or sperm and eggs in humans.

When sex cells are produced by a special cell division called meiosis, chromosomes exchange large segments of DNA. This ensures that each new cell has a unique genetic makeup and explains why, with the exception of identical twins, no two siblings are ever completely genetically alike. These exchanges of DNA, or crossovers, are essential for generating genetic diversity, the driving force for evolution, and their frequency and position along chromosomes are tightly controlled.

Co-first author of the study Dr. Chris Morgan explains the significance of this phenomenon: “Crossover positioning has important implications for evolution, fertility and selective breeding. By understanding the mechanisms that drive crossover positioning we are more likely to be able to uncover methods to modify crossover positioning to improve current plant and animal breeding technologies.”

In the latest of ongoing efforts to expand technologies for modifying genes and their expression, researchers have developed chemically modified guide RNAs for a CRISPR system that targets RNA instead of DNA. These chemically-modified guide RNAs significantly enhance the ability to target — trace, edit, and/or knockdown — RNA in human cells.

In a study published today in Cell Chemical Biology, the team explores a range of different RNA modifications and details how the modified guides increase efficiencies of CRISPR activity from 2-to 5-fold over unmodified guides. They also show that the optimized chemical modifications extend CRISPR targeting activity from 48 hours to four days. The researchers worked in collaboration with scientists at Synthego Corporation and New England BioLabs, bringing together a diverse team with expertise in enzyme purification and RNA chemistry. To apply these optimized chemical modifications, the research team targeted cell surface receptors in human T cells from healthy donors and a “universal” segment of the genetic sequence shared by all known variants of the RNA virus SARS-COV-2, which is responsible for the COVID-19 pandemic.

Increasing the efficiencies and “life” of CRISPR-Cas13 guides is of critical value to researchers and drug developers, allowing for better gene knockdown and more time to study how the gene influences other genes in related pathways.

“CRISPR RNA guide delivery can be challenging, with knockdown time limited due to rapid guide degradation. We were inspired by the guide modifications developed for other DNA-targeting CRISPRs and wanted to test if chemically modified guides could improve knockdown time for RNA-targeting CRISPR-Cas13 in human cells,” says Alejandro Méndez-Mancilla, PhD, a postdoctoral scientist in the lab and co-first author of the study.

Last week, a young woman with sickle cell anemia became the first person in the United States to have her cells altered with CRISPR gene editing technology. Here’s what that means for the future treatment of genetic diseases.