Category Archives: Transhuman News

Packaging of a genome in phage head
For more information, log on to- http://shomusbiology.weebly.com/ This bacteriophage lecture explains the bacteriophage genome assembly and the packaging of ...

By: Suman Bhattacharjee

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Packaging of a genome in phage head - Video

XROMA - CHROMOSOME 11 - HD - THE HUMAN GENOME MUSIC PROJECT
Chromosome 11 from The Human Genome Music Project by UK Composer Stuart Mitchell - Real-time Genome Music - 3000 BPM.

By: Stuart Mitchell Music

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XROMA - CHROMOSOME 11 - HD - THE HUMAN GENOME MUSIC PROJECT - Video

PUBLIC RELEASE DATE:

25-Apr-2014

Contact: Sue McGreevey smcgreevey@partners.org 617-724-2764 Massachusetts General Hospital

A next-generation genome editing system developed by Massachusetts General Hospital (MGH) investigators substantially decreases the risk of producing unwanted, off-target gene mutations. In a paper receiving online publication in Nature Biotechnology, the researchers report a new CRISPR-based RNA-guided nuclease technology that uses two guide RNAs, significantly reducing the chance of cutting through DNA strands at mismatched sites.

"This system combines the ease of use of the widely adopted CRISPR/Cas system with a dimerization-dependent nuclease activity that confers higher specificity of action," says J. Keith Joung, MD, PhD, associate chief for Research in the MGH Department of Pathology and senior author of the report. "Higher specificity will be essential for any future clinical use of these nucleases, and the new class of proteins we describe could provide an important option for therapeutic genome editing."

Engineered CRISPR-Cas nucleases genome-editing tools that combine a short RNA segment matching its DNA target with a DNA-cutting enzyme called Cas9 have been the subject of much investigation since their initial development in 2012. Easier to use than the earlier ZFN (zinc finger nuclease) and TALEN (transcription activator-like effector nuclease) systems, they have successfully induced genomic changes in several animal models systems and in human cells. But in a previous Nature Biotechnology paper published in June 2013, Joung's team reported that CRISPR-Cas nucleases could produce additional mutations in human cells, even at sites that differed from the DNA target by as much as five nucleotides.

To address this situation, the investigators developed a new platform in which the targeting function of Cas9 was fused to a nuclease derived from a well-characterized enzyme called Fokl, which only functions when two copies of the molecule are paired, a relationship called dimerization. This change essentially doubled the length of DNA that must be recognized for cleavage by these new CRISPR RNA-guided Fokl nucleases (RFNs), significantly increasing the precision of genome editing in human cells. Importantly, Joung and his colleagues also demonstrated that these new RFNs are as effective at on-target modification as existing Cas9 nucleases that target a shorter DNA sequence.

"By doubling the length of the recognized DNA sequence, we have developed a new class of genome -editing tools with substantially improved fidelity compared with existing wild-type Cas9 nucleases and nickases (enzymes that cleave a single DNA strand)," says Joung, an associate professor of Pathology at Harvard Medical School. The research team also has developed software enabling users to identify potential target sites for these RFNs and incorporated that capability into ZiFiT Targeter, a software package freely available at http://zifit.partners.org.

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Lead author of the Nature Biotechnology report is Shengdar Tsai, PhD, of the MGH Molecular Pathology Unit. Additional co-authors are Nicolas Wyvekens, Cyd Khayter, Jennifer Foden, Vishal Thapar, Deepak Reyon, PhD, Mathew Goodwin and Martin Aryee, PhD, all of MGH Molecular Pathology. The study was supported by National Institutes of Health Director's Pioneer Award DP1 GM105378; NIH grants R01 GM088040, P50 HG005550, and R01 AR063070; and by the Jim and Ann Orr Massachusetts General Hospital MGH Research Scholar Award. Joung is a co-founder of Editas Medicine, Inc., which has an exclusive option to license the new CRISPR RNA-guided Fokl nuclease technology for therapeutic applications.

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New genome-editing platform significantly increases accuracy of CRISPR-based systems

Large sections of the genome that were once referred to as "junk" DNA have been linked to human heart failure, according to research from Washington University School of Medicine in St. Louis.

So-called junk DNA was long thought to have no important role in heredity or disease because it doesn't code for proteins. But emerging research in recent years has revealed that many of these sections of the genome produce RNA molecules that, despite not being proteins, still have important functions in the body. RNA is a close chemical cousin to DNA.

Molecules now associated with these sections of the genome are called noncoding RNAs. They come in a variety of forms, some more widely studied than others. Of these, about 90 percent are called long noncoding RNAs, and exploration of their roles in health and disease is just beginning.

In a recent issue of the journal Circulation, Washington University investigators report results from the first comprehensive analysis of all RNA molecules expressed in the human heart. The researchers studied nonfailing hearts and failing hearts before and after patients received pump support from left ventricular assist devices (LVAD). The LVADs increased each heart's pumping capacity while patients waited for heart transplants.

"We took an unbiased approach to investigating which types of RNA might be linked to heart failure," said senior author Jeanne M. Nerbonne, PhD, the Alumni Endowed Professor of Molecular Biology and Pharmacology. "We were surprised to find that long noncoding RNAs stood out. In fact, the field is evolving so rapidly that when we did a slightly earlier, similar investigation in mice, we didn't even think to include long noncoding RNAs in the analysis."

Heart failure refers to a gradual loss of heart function. The left ventricle, the heart's main pumping chamber, becomes less efficient. Blood flow diminishes, and the body no longer receives the oxygen needed to go about daily tasks. Sometimes the condition develops after an obvious trigger such as a heart attack or infection, but other times the causes are less clear.

In the new study, the investigators found that unlike other RNA molecules, expression patterns of long noncoding RNAs could distinguish between two major types of heart failure and between failing hearts before and after they received LVAD support.

"We don't know whether these changes in long noncoding RNAs are a cause or an effect of heart failure," Nerbonne said. "But it seems likely they play some role in coordinating the regulation of multiple genes involved in heart function."

Nerbonne pointed out that all types of RNA molecules they examined could make the obvious distinction: telling the difference between failing and nonfailing hearts. But only expression of the long noncoding RNAs was measurably different between heart failure associated with a heart attack (ischemic) and heart failure without the obvious trigger of blocked arteries (nonischemic). Similarly, only long noncoding RNAs significantly changed expression patterns after implantation of left ventricular assist devices.

Because of the difficulty in obtaining human heart tissue, the study's sample size was relatively small, Nerbonne said. Her team analyzed eight nonfailing hearts, eight hearts in ischemic heart failure and eight hearts in nonischemic heart failure. Though small, the study is unique because each of the 16 failing hearts was sampled twice, once before and once after LVAD support.

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Genome regions once mislabeled 'junk' linked to heart failure