Lifeboat Foundation

Humans perceive the world around them with five senses — vision, hearing, taste, smell and touch. Many other animals are also able to sense the Earth’s magnetic field. For some time, a collaboration of biologists, chemists and physicists centred at the Universities of Oldenburg (Germany) and Oxford (UK) have been gathering evidence suggesting that the magnetic sense of migratory birds such as European robins is based on a specific light-sensitive protein in the eye. In the current edition of the journal Nature, this team demonstrate that the protein cryptochrome 4, found in birds’ retinas, is sensitive to magnetic fields and could well be the long-sought magnetic sensor.

First author Jingjing Xu, a doctoral student in Henrik Mouritsen’s research group in Oldenburg, took a decisive step toward this success. After extracting the genetic code for the potentially magnetically sensitive cryptochrome 4 in night-migratory European robins, she was able, for the first time, to produce this photoactive molecule in large quantities using bacterial cell cultures. Christiane Timmel’s and Stuart Mackenzie’s groups in Oxford then used a wide range of magnetic resonance and novel optical spectroscopy techniques to study the protein and demonstrate its pronounced sensitivity to magnetic fields.

The team also deciphered the mechanism by which this sensitivity arises — another important advance. “Electrons that can move within the molecule after blue-light activation play a crucial role,” explains Mouritsen. Proteins like cryptochrome consist of chains of amino acids: robin cryptochrome 4 has 527 of them. Oxford’s Peter Hore and Oldenburg physicist Ilia Solov’yov performed quantum mechanical calculations supporting the idea that four of the 527 — known as tryptophans — are essential for the magnetic properties of the molecule. According to their calculations, electrons hop from one tryptophan to the next generating so-called radical pairs which are magnetically sensitive. To prove this experimentally, the team from Oldenburg produced slightly modified versions of the robin cryptochrome, in which each of the tryptophans in turn was replaced by a different amino acid to block the movement of electrons.

The new system streamlines the process of fermenting plant sugar to fuel by helping yeast survive industrial toxins.

More corn is grown in the United States than any other crop, but we only use a small part of the plant for food and fuel production; once people have harvested the kernels, the inedible leaves, stalks and cobs are left over. If this plant matter, called corn stover, could be efficiently fermented into ethanol the way corn kernels are, stover could be a large-scale, renewable source of fuel.

“Stover is produced in huge amounts, on the scale of petroleum,” said Whitehead Institute Member and Massachusetts Institute of Technology (MIT) biology professor Gerald Fink. “But there are enormous technical challenges to using them cheaply to create biofuels and other important chemicals.”

CRISPR gene editing already promises to fight diseases that were once thought unassailable, but techniques so far have required injecting the tools directly into affected cells. That’s not very practical for some conditions. However, there’s just been a breakthrough. NPR reports that researchers have published results showing that you can inject CRISPR-Cas9 into the bloodstream to make edits, opening the door to the use of gene editing for treating many common diseases.

The experimental treatment tackled a rare genetic disease, transthyretin amyloidosis. Scientists injected volunteers with CRISPR-loaded nanoparticles that were absorbed by the patients’ livers, editing a gene in the organ to disable production of a harmful protein. Levels of that protein plunged within weeks of the injection, saving patients from an illness that can rapidly destroy nerves and other tissues in their bodies.

The test involved just six people, and the research team still has to conduct long-term studies to check for possible negative effects. If this method proves viable on a large scale, though, it could be used to treat illnesses where existing CRISPR techniques aren’t practical, ranging from Alzheimer’s to heart disease.

Now, in a medical first, researchers have injected a CRISPR drug into the blood of people born with a disease that causes fatal nerve and heart disease and shown that in three of them it nearly shut off production of toxic protein by their livers.

Novel treatment using messenger RNA sharply cuts production of mutant liver protein, although it’s too early to show patients with rare condition benefit.

👏😄We are rapidly approaching — from multiple directions of attack (pharmaceutical, nanotechnology, gene manipulation, etc) — the end of all forms of cancer, inherited diseases, even aging itself. It’s a great time to be alive IF you can live long enough to live forever(ish)! Which makes EVERY death that occurs in the meantime to be all the more of a punch to the gut and slap to the face. PARTICULARLY the 600 000 + people here in the US alone! It’s also another reason t… See More.

If the gene-editing tool CRISPR/Cas9 continues to show such promise it will herald a new era for the treatment of many genetic diseases.

Scientists successfully treated a rare disease with the experimental gene-editing technique. It could open the door to new ways of treating more common disorders in the future.

Move over, gene-editing proteins—there’s a smaller, cheaper, more specific genetic engineering tool on the block: DNAzymes—small DNA molecules that can function like protein enzymes.

Researchers at the University of Illinois Urbana-Champaign have developed a technique that, for the first time, allows DNAzymes to target and cut double-stranded DNA, overcoming a significant limitation of the technology. DNAzymes have been used in biosensing, DNA computing and many other applications. However, when it comes to genetic engineering applications such as gene editing or gene therapy, they have faced a challenge: DNAzymes have only been able to target sites on single-stranded DNA, while the DNA coding for genes in cells is double-stranded. The researchers published their new technique in the Journal of the American Chemical Society.

“DNAzymes have many advantages, including higher stability, smaller size and lower cost than protein enzymes. These advantages perfectly fit the requirement for genetic engineering tools,” said study leader Yi Lu, a professor of chemistry at Illinois. “No DNAzymes could alter double-stranded DNA until this work. By making that happen, we open the door for DNAzymes to enter the entire world of genetic engineering.”

To understand how the clones can create millions of copies of themselves and yet remain functional, Oldroyd and his team compared the genomes of Cape honeybee workers with those of their queen and her offspring.

After forcing the Cape queen to reproduce asexually by fitting her with surgical tape that prevented her from mating, the team examined certain DNA sequences of both the Cape queen and the 25 larvae she produced. Then, they did the same for four Cape honeybee workers and their 63 larvae.

The team discovered that the asexually reproduced offspring of the queen had levels of recombination (DNA mixing) 100 times greater than the genetically identical cloned offspring of the workers — a finding that suggests the Cape worker bees have evolved a mutation that prevents recombination. Without the risk of a one-third loss of genetic material caused by the asexual reshuffling process, the workers are free to continually create perfect copies of themselves.

Genome-embedded ribonucleotides arrest replicative DNA polymerases (Pols) and cause DNA breaks. Whether mammalian DNA repair Pols efficiently use template ribonucleotides and promote RNA-templated DNA repair synthesis remains unknown. We find that human Polθ reverse transcribes RNA, similar to retroviral reverse transcriptases (RTs). Polθ exhibits a significantly higher velocity and fidelity of deoxyribonucleotide incorporation on RNA versus DNA. The 3.2-Å crystal structure of Polθ on a DNA/RNA primer-template with bound deoxyribonucleotide reveals that the enzyme undergoes a major structural transformation within the thumb subdomain to accommodate A-form DNA/RNA and forms multiple hydrogen bonds with template ribose 2′-hydroxyl groups like retroviral RTs. Last, we find that Polθ promotes RNA-templated DNA repair in mammalian cells. These findings suggest that Polθ was selected to accommodate template ribonucleotides during DNA repair.

Polymerase θ (Polθ) is a unique DNA polymerase-helicase fusion protein in higher eukaryotes whose A-family polymerase domain evolved from Pol I enzymes (Fig. 1A) (1, 2). However, contrary to most Pol I enzymes, Polθ is highly error-prone and promiscuous (3–6), performs translesion synthesis (TLS) opposite DNA lesions (3, 7, 8), and facilitates microhomology-mediated end-joining (MMEJ) of double-strand breaks (DSBs) by extending partially base-paired 3′ single-stranded DNA (ssDNA) overhangs at DSB repair junctions (5, 9–12). Polθ is not expressed in most tissues but is highly expressed in many cancer cells, which corresponds to a poor clinical outcome (13, 14). Furthermore, Polθ confers resistance to genotoxic cancer therapies and promotes the survival of cells deficient in DNA damage response pathways (11, 13–16). Thus, Polθ represents a promising cancer drug target.

Intriguingly, Polθ has an inactive proofreading domain due to acquired mutations (Fig. 1A) (2). Inactivating the 3′-5′ proofreading function of closely related A-family bacterial Pol I Klenow fragment (KF) enables this polymerase to reverse transcribe RNA like retroviral reverse transcriptases (RTs), which lack proofreading activity (fig. S1A) (17, 18). Because Polθ is highly error-prone and promiscuous and contains an inactive proofreading domain, we hypothesized that it has RNA-dependent DNA synthesis activity. Given that ribonucleotides are the most frequently occurring nucleotide lesion in genomic DNA that arrest replicative Pols and cause DNA breaks (19, 20), we also envisaged that Polθ would tolerate template ribonucleotides during its DNA repair activities and thus promote RNA-templated DNA repair synthesis (RNA-DNA repair). Although RNA-DNA repair mechanisms have been demonstrated in genetically engineered yeast cells (21, 22), they remain obscure in mammalian cells.