CRISPR meets machine learning

If a donor template is not provided when CRISPR cuts the DNA, broken ends are fixed by natural repairing mechanisms in a way that is considered stochastic and heterogeneous. This makes template-free editing impractical beyond gene disruption, right? Wrong, according to a study published in Nature by Richard Sherwood and colleagues. Continue reading

Picture of the week

bimaternal pups

Healthy adult bimaternal mouse (born to two mothers) with offspring of her own.
Credit: Leyun Wang

Single-gender worlds will remain a sci-fi fantasy. Gay and lesbian couples won’t become parents this way for the foreseeable future. This kind of manipulation is just too risky for humans. But unisexually reproducing mice are an impressive accomplishment, and CRISPR stands out again as a powerful research tool, opening up brand new possibilities for the study of genomic imprinting. For further details, please see the STAT News article about the Cell Stem Cell paper by Zhi-Kun Li.

Anti-CRISPR and the Red Queen

red queen

The battle for survival between bacteria and bacteriophages can be framed according to the Red Queen hypothesis. To avoid extinction bacteria must evolve new mechanisms of resistance, such as CRISPR immunity. Viruses, in turn, must evolve countermeasures to inactivate these resistance mechanisms, such as anti-CRISPR proteins. These natural inhibitors may well become biotech tools useful to keep genome-editing in check and are a minefield waiting to be explored. Jennifer Doudna and Joseph Bondy-Denomy used bioinformatics to find some of them, and have just published their findings in Science. Paraphrasing Dobzhansky’s famous dictum, nothing in biotechnology makes sense except in the light of evolution.

CRISPRing the Neanderthal’s mind

Neanderthal_minibrains

Sapiens vs Neanderthalized brain organoids (credit A. Muotri)

Taking a peek into the brain of a Neanderthal specimen would be a dream for whoever is interested in the evolution of human intelligence. To get an idea of the cognitive abilities of our closest relatives, so far, anthropologists and neuroscientists could only study the fossil and archaeological record, but a new exciting frontier is opening up where paleogenetics meets organoids and CRISPR technologies. By combining these approaches, two labs are independently developing mini-brains from human pluripotent stem cells edited to carry Neanderthal mutations. Alysson Muotri did it at UC San Diego, as Jon Cohen reported in Science last week. Svante Pääbo is doing it at the Max Planck Institute in Leipzig, as revealed by The Guardian in May. Forget George Church’s adventurous thoughts on cloning Neanderthals. The purpose here is to answer one of the most captivating questions ever asked: did the mind of these ancient men and women, who interbred with our sapiens ancestors before going extinct, work differently from ours? Last but not least, with respect to the ethics of experimenting with mini-brains, don’t miss the perspective published in Nature.

CRISPR diving the coral reef

coral-bleachingThey are not super-corals genetically edited to repopulate the reef. However, the Acropora millepora described in PNAS last week are the first baby polyps ever CRISPRed in a lab, by a team involving Stanford University, UT-Austin and the Australian Institute of Marine Science in Townsville. These uncontroversial organisms pave the way for future experiments to reveal the molecular basis of vulnerability to bleaching, the fatal loss of algal symbionts triggered by global warming. Most corals reproduce once or twice a year, ejecting huge quantities of sex cells resembling underwater snowflakes. The time window of these spawning events can be predicted quite accurately, so researchers can sample the reef at the right moment and collect early embryos for genetic manipulation. We discussed the experiment results and future perspectives of gene editing in corals with the paper’s first author Phil Cleves.

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Playing a three of CRISPR kind

three acesIt is Science but it could be mistaken for The CRISPR Journal. The latest issue indeed runs three papers by three CRISPR aces – David Liu, Jennifer Doudna, and Feng Zhang – about the cutting-edge fields of biological recorders and advanced diagnostic tests. Continue reading

Rec-Stop-Play: CRISPR becomes a biological recorder

biological recorder 2When using a standard tape recorder you just have to press the buttons. Now a Columbia University team has devised a system for doing the same in living systems, recording changes taking place inside the cells. How does it work? This biological recorder, described in a study appearing in Science, is called TRACE and may help us chronicle what happens in open settings such as marine environments or in habitats difficult to access such as the mammalian gut. It records molecular fluctuations instead of sounds, capturing metabolic dynamics, gene expression changes and lineage-associated information across cell populations. The medium is DNA rather than magnetic tape. Sequencing is like playing. But how is the DNA recording done? Continue reading