Lifeboat Foundation

RNA-binding proteins (RBPs) are critical effectors of gene expression, and as such their malfunction underlies the origin of many diseases. RBPs can recognize hundreds of transcripts and form extensive regulatory networks that help to maintain cell homeostasis. System-wide unbiased identification of RBPs has increased the number of recognized RBPs into the four-digit range and revealed new paradigms: from the prevalence of structurally disordered RNA-binding regions with roles in the formation of membraneless organelles to unsuspected and potentially pervasive connections between intermediary metabolism and RNA regulation. Together with an increasingly detailed understanding of molecular mechanisms of RBP function, these insights are facilitating the development of new therapies to treat malignancies. Here, we provide an overview of RBPs involved in human genetic disorders, both Mendelian and somatic, and discuss emerging aspects in the field with emphasis on molecular mechanisms of disease and therapeutic interventions.

Researchers at Lund University in Sweden have discovered a new method to treat human herpes viruses. The new broad-spectrum method targets physical properties in the genome of the virus rather than viral proteins, which have previously been targeted. The treatment consists of new molecules that penetrate the protein shell of the virus and prevent genes from leaving the virus to infect the cell. It does not lead to resistance and acts independently of mutations in the genome of the virus. The results are published in the journal PLOS Pathogens.

Herpes virus infections are lifelong, with latency periods between recurring reactivations, making treatment difficult. The major challenge lies in the fact that all existing antiviral drugs to treat herpes viruses lead to rapid development of resistance in patients with compromised immune systems where the need for herpes treatment is the greatest (e.g. newborn children, patients with HIV, cancer or who have undergone organ transplantation). Both the molecular and physical properties of a virus determine the course of infection. However, the physical properties have so far received little attention, according to researcher Alex Evilevitch.

“We have a new and unique approach to studying viruses based on their specific physical properties. Our discovery marks a breakthrough in the development of antiviral drugs as it does not target specific viral proteins that can rapidly mutate, causing the development of drug resistance — something that remains unresolved by current antiviral drugs against herpes and other viruses. We hope that our research will contribute to the fight against viral infections that have so far been incurable,” says Alex Evilevitch, Associate Professor and senior lecturer at Lund University who, together with his research team, Virus Biophysics, has published the new findings.

Although Drosophila is an insect whose genome has only about 14,000 genes, roughly half the human count, a remarkable number of these have very close counterparts in humans; some even occur in the same order in the fly’s DNA as in our own. This, plus the organism’s more than 100-year history in the lab, makes it one of the most important models for studying basic biology and disease.

To take full advantage of the opportunities offered by Drosophila, researchers need improved tools to manipulate the fly’s genes with precision, allowing them to introduce mutations to break genes, control their activity, label their protein products, or introduce other inherited genetic changes.

“We now have the genome sequences of lots of different animals — worms, flies, fish, mice, chimps, humans,” says Roger Hoskins of Berkeley Lab’s Life Sciences Division. “Now we want improved technologies for introducing precise changes into the genomes of lab animals; we want efficient genome engineering. Methods for doing this are very advanced in bacteria and yeast. Good methods for worms, flies, and mice have also been around for a long time, and improvements have come along fairly regularly. But with whole genome sequences in hand, the goals are becoming more ambitious.”

O,.o Circa 2019

CRISPR/Cas9 is now a household name associated with genetic engineering studies. Through cutting-edge research described in their paper published in Scientific Reports, a team of researchers from Tokyo University of Science, Meiji University, and Tokyo University of Agriculture and Technology, led by Dr Takayuki Arazoe and Prof Shigeru Kuwata, has recently established a series of novel strategies to increase the efficiency of targeted gene disruption and new gene “introduction” using the CRISPR/Cas9 system in the rice blast fungus Pyricularia (Magnaporthe) oryzae. These strategies include quicker (single-step) gene introduction, use of small homologous sequences, and bypassing of certain prerequisite host DNA “patterns” and host component modification.

The team led by Dr Arazoe and Prof Kuwata has devised simple and quick techniques for gene editing (target gene disruption, sequence substitution, and re-introduction of desired genes) using CRISPR/Cas9 in the rice blast fungus Pyricularia (Magnaporthe) oryzae, a type of filamentous fungus. Spurred on by encouraging results, the researchers surmise, “Plants and their pathogens are still coevolving in nature. Exploiting the mutation mechanisms of model pathogenic fungi as a genome editing technique might lead to the development of further novel techniques in genetic engineering.”

The working component of the CRISPR/Cas9 system binds to the target gene region (DNA) and causes a site-specific double-stranded break (DSB) in the DNA. Effective binding of this component requires a certain “motif” or “pattern” called the protospacer-adjacent motif (PAM), which follows downstream of the target gene region.

For more than two decades, I have been working to improve several staple food crops in Africa, including bananas, plantains, cassavas and yams. As principal scientist and a plant biotechnologist at the International Institute for Tropical Agriculture in Nairobi, I aim to develop varieties that are resistant to pests and diseases such as bacterial wilt, Fusarium wilt (caused by the fungus F. oxysporum) and banana streak virus.

[Editor’s note: Abdullahi Tsanni is a freelance science journalist based in Abuja, Nigeria.]

In 2011, my team and I created a set of tools, the only one of its kind in Africa, for changing DNA sequences so that we could develop genetically modified and genome-edited products in sub-Saharan Africa. In 2018, we pioneered the first application of CRISPR gene-editing technology to deactivate banana streak virus in plantains. This technology overcame a major hurdle in banana breeding on the continent, and is the first reported successful use of genome editing to improve bananas.

The honeybee (Apis mellifera) is an important insect pollinator of wild flowers and crops, playing critical roles in the global ecosystem. Additionally, the honeybee serves as an ideal social insect model. Therefore, functional studies on honeybee genes are of great interest. However, until now, effective gene manipulation methods have not been available in honeybees. Here, we reported an improved CRISPR/Cas9 gene-editing method by microinjecting sgRNA and Cas9 protein into the region of zygote formation within 2 hr after queen oviposition, which allows one-step generation of biallelic knockout mutants in honeybee with high efficiency. We first targeted the Mrjp1 gene. Two batches of honeybee embryos were collected and injected with Mrjp1 sgRNA and Cas9 protein at the ventral cephalic side and the dorsal posterior side of the embryos, respectively. The gene-editing rate at the ventral cephalic side was 93.3%, which was much higher than that (11.8%) of the dorsal-posterior-side injection. To validate the high efficiency of our honeybee gene-editing system, we targeted another gene, Pax6, and injected Pax6 sgRNA and Cas9 protein at the ventral cephalic side in the third batch. A 100% editing rate was obtained. Sanger sequencing of the TA clones showed that 73.3% (for Mrjp1) and 76.9% (for Pax6) of the edited current-generation embryos were biallelic knockout mutants. These results suggest that the CRISPR/Cas9 method we established permits one-step biallelic knockout of target genes in honeybee embryos, thereby demonstrating an efficient application to functional studies of honeybee genes. It also provides a useful reference to gene editing in other insects with elongated eggs.

Initially discovered in bacteria, CRISPR-based genome editing endonucleases have proven remarkably amenable for adaptation to insects. To date, these endonucleases have been utilized in a plethora of both model and non-model insects including diverse flies, bees, beetles, butterflies, moths, and grasshoppers, to name a few, thereby revolutionizing functional genomics of insects. In addition to basic genome editing, they have also been invaluable for advanced genome engineering and synthetic biology applications. Here we explore the recent genome editing advancements in insects for generating site-specific genomic mutations, insertions, deletions, as well as more advanced applications such as Homology Assisted Genome Knock-in (HACK), potential to utilize DNA base editing, generating predictable reciprocal chromosomal translocations, and development gene drives to control the fate of wild populations.

Researchers in Australia are shining a spotlight on a safer delivery method for targeted CRISPR gene therapies—and they’re using literal illumination to pull it off.

Scientists and biomedical engineers from the University of New South Wales Sydney say they’ve developed a light-sensitive liposome that can ferry CRISPR molecules to specific sites in the body. When hit with LED light, the liposomes unleash their CRISPR payloads to hunt down faulty genes.

The CRISPR-Cas9 gene-editing tool consists of a guide RNA that homes in on a target in the DNA, and the Cas9 enzyme, which cuts the DNA much like a pair of molecular scissors. A slate of companies is exploring the technology to treat cancer and even blindness, but the therapy is traditionally delivered using viruses, which can themselves spur unwanted immune responses and other side effects.

Senescence in cancer cells

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Sometimes, too much of a good thing can turn out to be bad. This is certainly the case for the excessive cell growth found in cancer. But when cancers try to grow too fast, this excessive speed can cause a type of cellular aging that actually results in arrested growth. Scientists at Duke-NUS Medical School have now discovered that a well-known signaling pathway helps cancers grow by blocking the pro-growth signals from a second major cancer pathway.

Continue reading “Getting it just right: The Goldilocks model of cancer” »