| Weill Cornell Medicine and New York Genome Center researchers, in collaboration with Oxford Nanopore Technologies, have developed a new method to assess on a large scale the three-dimensional structure of the human genome, or how the genome folds. The genome is the complete set of genetic instructions, DNA or RNA, enabling an organism to function. | |
| Using this method, the researchers demonstrated that cell function, including gene expression, may be affected by groups of simultaneously interacting regulatory elements in the genome rather than pairs of these components. Their findings, published in Nature Biotechnology (“Team architecture in 3D genomic interactions revealed through nanopore sequencing”), may help shed light on the relationship between genome structure and cellular identity. | |
| “Knowing the three-dimensional genome structure will help researchers better understand how the genome functions, and particularly how it encodes different cell identities,” said senior author Dr. Marcin Imieliński, associate professor of pathology and laboratory medicine and computational genomics in computational biomedicine at Weill Cornell Medicine and a core member of the New York Genome Center. “The ways that we’ve had to study genome structure have given us amazing insights, but there have also been key limitations,” he said. | |
| For example, previous technology to assess the genome’s three-dimensional structure has allowed researchers to study how frequently two loci, or physical locations on the genome, interact with one another. Traditionally, pairs of loci called enhancers and promoters – components in the genome that interact with one another to influence gene expression – have been observed. | |
| Information about these pairings offers incomplete insight into genome structure and function. For instance, linking a folding pattern to how the genome encodes for a specific cell identity – like a liver, lung or epithelial cell – has been difficult, said Imieliński, who is also a member of the Englander Institute for Precision Medicine and the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine. Scientists have theorized that this folding influences gene expression. “But how cell types are encoded, particularly in the structure of DNA, has been a mystery,” he said. | |
| Imieliński and his research team, including first author Aditya Deshpande, a recent graduate of the Tri-Institutional Ph.D. Program in Computational Biology & Medicine working in Imieliński’s lab, developed a new genome-wide assay and algorithm that allows them to study groups of loci, not just pairs. | |
| They adapted a traditional technology, Hi-C (chromatin conformation capture), which assesses a mixture of DNA and protein to analyze three-dimensional genome structure, to nanopore sequencing, or the high-throughput sequencing of long, continuous strands of DNA molecules. The resulting assay, which the researchers called Pore-C, enabled them to observe tens of millions of three-dimensional locus groupings. | |
| They also developed statistical methods to determine which locus groupings were important, based on whether they interacted cooperatively to affect gene expression. “Many three-dimensional interactions of the genome are not important,” Imieliński said. “Our analytic methods help us prioritize the group interactions that are likely to matter for genome function.” As a key finding of the study, the researchers found that the most significant cooperative groupings of DNA elements occurred around genes associated with cell identity. | |
| Future experiments will explore which specific groupings of genomic components are essential for various aspects of cell identity. The new technology may also help researchers to understand how stem cells, the immature, master cells of the body, differentiate into different cell types. | |
| In addition, researchers may be better able understand abnormalities in cancer cells. “In the future, this technology may be really helpful in understanding how cancer cell genomes are rearranged, and how those rearrangements drive the altered cell identities that enable cancers to grow and spread” Imieliński said. |
News
Scientists Melt Cancer’s Hidden “Power Hubs” and Stop Tumor Growth
Researchers discovered that in a rare kidney cancer, RNA builds droplet-like hubs that act as growth control centers inside tumor cells. By engineering a molecular switch to dissolve these hubs, they were able to halt cancer [...]
Platelet-inspired nanoparticles could improve treatment of inflammatory diseases
Scientists have developed platelet-inspired nanoparticles that deliver anti-inflammatory drugs directly to brain-computer interface implants, doubling their effectiveness. Scientists have found a way to improve the performance of brain-computer interface (BCI) electrodes by delivering anti-inflammatory drugs directly [...]
After 150 years, a new chapter in cancer therapy is finally beginning
For decades, researchers have been looking for ways to destroy cancer cells in a targeted manner without further weakening the body. But for many patients whose immune system is severely impaired by chemotherapy or radiation, [...]
Older chemical libraries show promise for fighting resistant strains of COVID-19 virus
SARS‑CoV‑2, the virus that causes COVID-19, continues to mutate, with some newer strains becoming less responsive to current antiviral treatments like Paxlovid. Now, University of California San Diego scientists and an international team of [...]
Lower doses of immunotherapy for skin cancer give better results, study suggests
According to a new study, lower doses of approved immunotherapy for malignant melanoma can give better results against tumors, while reducing side effects. This is reported by researchers at Karolinska Institutet in the Journal of the National [...]
Researchers highlight five pathways through which microplastics can harm the brain
Microplastics could be fueling neurodegenerative diseases like Alzheimer's and Parkinson's, with a new study highlighting five ways microplastics can trigger inflammation and damage in the brain. More than 57 million people live with dementia, [...]
Tiny Metal Nanodots Obliterate Cancer Cells While Largely Sparing Healthy Tissue
Scientists have developed tiny metal-oxide particles that push cancer cells past their stress limits while sparing healthy tissue. An international team led by RMIT University has developed tiny particles called nanodots, crafted from a metallic compound, [...]
Gold Nanoclusters Could Supercharge Quantum Computers
Researchers found that gold “super atoms” can behave like the atoms in top-tier quantum systems—only far easier to scale. These tiny clusters can be customized at the molecular level, offering a powerful, tunable foundation [...]
A single shot of HPV vaccine may be enough to fight cervical cancer, study finds
WASHINGTON -- A single HPV vaccination appears just as effective as two doses at preventing the viral infection that causes cervical cancer, researchers reported Wednesday. HPV, or human papillomavirus, is very common and spread [...]
New technique overcomes technological barrier in 3D brain imaging
Scientists at the Swiss Light Source SLS have succeeded in mapping a piece of brain tissue in 3D at unprecedented resolution using X-rays, non-destructively. The breakthrough overcomes a long-standing technological barrier that had limited [...]
Scientists Uncover Hidden Blood Pattern in Long COVID
Researchers found persistent microclot and NET structures in Long COVID blood that may explain long-lasting symptoms. Researchers examining Long COVID have identified a structural connection between circulating microclots and neutrophil extracellular traps (NETs). The [...]
This Cellular Trick Helps Cancer Spread, but Could Also Stop It
Groups of normal cbiells can sense far into their surroundings, helping explain cancer cell migration. Understanding this ability could lead to new ways to limit tumor spread. The tale of the princess and the [...]
New mRNA therapy targets drug-resistant pneumonia
Bacteria that multiply on surfaces are a major headache in health care when they gain a foothold on, for example, implants or in catheters. Researchers at Chalmers University of Technology in Sweden have found [...]
Current Heart Health Guidelines Are Failing To Catch a Deadly Genetic Killer
New research reveals that standard screening misses most people with a common inherited cholesterol disorder. A Mayo Clinic study reports that current genetic screening guidelines overlook most people who have familial hypercholesterolemia, an inherited disorder that [...]
Scientists Identify the Evolutionary “Purpose” of Consciousness
Summary: Researchers at Ruhr University Bochum explore why consciousness evolved and why different species developed it in distinct ways. By comparing humans with birds, they show that complex awareness may arise through different neural architectures yet [...]
Novel mRNA therapy curbs antibiotic-resistant infections in preclinical lung models
Researchers at the Icahn School of Medicine at Mount Sinai and collaborators have reported early success with a novel mRNA-based therapy designed to combat antibiotic-resistant bacteria. The findings, published in Nature Biotechnology, show that in [...]
