Lifeboat Foundation

A bold project to read the complete genetic sequences of every known vertebrate species reaches its first milestone by publishing new methods and the first 25 high-quality genomes.

It’s one of the most audacious projects in biology today – reading the entire genome of every bird, mammal, lizard, fish, and all other creatures with backbones.

And now comes the first major payoff from the Vertebrate Genomes Project (VGP): near complete, high-quality genomes of 25 species, Howard Hughes Medical Institute (HHMI) Investigator Erich Jarvis with scores of coauthors report April 28, 2021, in the journal Nature. These species include the greater horseshoe bat, the Canada lynx, the platypus, and the kākāpō parrot – one of the first high-quality genomes of an endangered vertebrate species.

An acquired mutation in the cancer-causing gene PIK3CA can make blood vessel malformations in the brain worse, possibly explaining why these abnormal clusters sometimes rapidly increase in size and cause stroke or seizures, shows new research.

Research from the University of Pennsylvania and Duke University shows an acquired mutation in the cancer-causing gene PIK3CA can trigger uncontrolled growth in cerebral cavernous malformations often leading to strokes or seizures in those affected.

While the CRISPR-Cas9 gene editing system has become the poster child for innovation in synthetic biology, it has some major limitations. CRISPR-Cas9 can be programmed to find and cut specific pieces of DNA, but editing the DNA to create desired mutations requires tricking the cell into using a new piece of DNA to repair the break. This bait-and-switch can be complicated to orchestrate, and can even be toxic to cells because Cas9 often cuts unintended, off-target sites as well.

Alternative gene editing techniques called recombineering instead perform this bait-and-switch by introducing an alternate piece of DNA while a cell is replicating its genome, efficiently creating genetic mutations without breaking DNA. These methods are simple enough that they can be used in many cells at once to create complex pools of mutations for researchers to study. Figuring out what the effects of those mutations are, however, requires that each mutant be isolated, sequenced, and characterized: a time-consuming and impractical task.

Researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University and Harvard Medical School (HMS) have created a new gene editing tool called Retron Library Recombineering (RLR) that makes this task easier. RLR generates up to millions of mutations simultaneously, and “barcodes” mutant cells so that the entire pool can be screened at once, enabling massive amounts of data to be easily generated and analyzed. The achievement, which has been accomplished in bacterial cells, is described in a recent paper in PNAS.

Mitochondria are the energy suppliers of our body cells. These tiny cell components have their own genetic material, which triggers an inflammatory response when released into the interior of the cell. The reasons for the release are not yet known, but some cardiac and neurodegenerative diseases as well as the aging process are linked to the mitochondrial genome. Researchers at the Max Planck Institute for Biology of Aging and the CECAD Cluster of Excellence in Aging research have investigated the reasons for the release of mitochondrial genetic material and found a direct link to cellular metabolism: when the cell’s DNA building blocks are in short supply, mitochondria release their genetic material and trigger inflammation. The researchers hope to find new therapeutic approaches by influencing this metabolic pathway.

Our body needs energy—for every metabolic process, every movement and for breathing. This energy is produced in tiny components of our body cells, the so-called mitochondria. Unlike other cell components, mitochondria have their own genetic material, mitochondrial DNA. However, in certain situations, mitochondria release their DNA into the interior of the cell, causing a reaction from the cell’s own immune system and being associated with various diseases as well as the aging process. The reasons for the release of mitochondrial DNA are not yet known.

The findings are published around the 35th anniversary of the nuclear disaster.

But the biotech industry has argued that much of gene-editing simply accelerates processes that occur naturally, and that GMO-style regulation would shackle efforts to develop sustainable crops or advance research into human disease.

The European Commission launched a review of EU rules on genetically modified organisms (GMOs) on Thursday, opening the door to a possible loosening of restrictions for plants resulting from gene-editing technology.

Prompted by a 2018 ruling from the European Union’s top court that techniques to alter the genome of an organism should be governed by existing EU rules on GMOs, the Commission concluded that its 2001 legislation was “not fit for purpose”.

Continue reading “EU calls for rethink of GMO rules for gene-edited crops” »

O,.o What a cure for cancer! o.o

Researchers are leveraging the messenger RNA (mRNA) technology used to develop the Pfizer-BioNTech and Moderna COVID-19 vaccines for possible treatments for a range of other diseases, including HIV and cancer.

This has long been thought possible with mRNA technology, but infectious diseases were something of the low-hanging fruit, and the COVID-19 pandemic drove the innovations.

Continue reading “MRNA Tech Used in COVID-19 Vaccines Could be Used to Cure HIV, Cancer and More” »

Why not add a light switch instead?

This month, a team from the University of California, San Francisco (UCSF) reimagined CRISPR to do just that. Rather than directly acting on genes—irrevocably dicing away or swapping genetic letters— the new CRISPR variant targets the biological machinery that naturally turns genes on or off.

Translation? CRISPR can now “flip a light switch” to control genes—without ever touching them directly. It gets better. The new tool, CRISPRoff, can cause a gene to stay silent for hundreds of generations, even when its host cells morph from stem cells into more mature cells, such as neurons. Once the “sleeping beauty” genes are ready to wake up, a complementary tool, CRISPRon, flips the light switch back on.

Cryopreservation, or the long-term storage of biomaterials at ultralow temperatures, has been used across cell types and species. However, until now, the practical cryopreservation of the fruit fly (Drosophila melanogaster)—which is crucial to genetics research and critical to scientific breakthroughs benefiting human health—has not been available.

“To keep alive the ever-increasing number of fruit flies with unique genotypes that aid in these breakthroughs, some 160000 different flies, laboratories and stock centers engage in the costly and frequent transfer of adults to fresh food, risking contamination and genetic drift,” said Li Zhan, a postdoctoral associate with the University of Minnesota College of Science and Engineering and the Center for Advanced Technologies for the Preservation of Biological Systems (ATP-Bio).

In new research published in Nature Communications, a University of Minnesota team has developed a first-of-its-kind method that cryopreserves fruit fly embryos so they can be successfully recovered and developed into adult insects. This method optimizes embryo permeabilization and age, cryoprotectant agent composition, different phases of nitrogen (liquid vs. slush), and post-cryopreservation embryo culture methods.