Lifeboat Foundation

Coronaviruses have brought about three massive outbreaks in the past two decades. Each step of its life cycle invariably depends on the interactions among virus and host molecules. The interaction between virus RNA and host protein (IVRHP) is unique compared to other virus-host molecular interactions, and has emerged to be a very hot topic in recent studies.

These studies provide essential information for a deeper understanding of IVRHP, which represents not only an attempt by viruses to promote their translation/replication, but also the host’s endeavor to combat viral pathogenicity. In other words, there is an urgent need to have a panorama of coronavirus RNA-Host protein interactions, which will then aid in the discovery of new antiviral therapies.

On October 6, 2022, Prof. Zhu Feng from College of Pharmaceutical Sciences in Zhejiang University, Prof. Han Lianyi from College of Life Sciences in Fudan University and Prof. Lin Tao from College of Pharmaceutical Sciences in Hangzhou Normal University published an article titled “CovInter: Interaction Data between Coronavirus RNAs and Host Proteins” in Nucleic Acids Research.

A team of scientists at Whitehead Institute and the Broad Institute of MIT and Harvard have systematically evaluated the functions of more than 5,000 essential human genes using a novel, pooled, imaged-based screening method. Their analysis harnesses CRISPR/Cas9 to knock out gene activity and forms a first-of-its-kind resource for understanding and visualizing gene function in a wide range of cellular processes with both spatial and temporal resolution.

The team’s findings, published in the journal Cell, span over 31 million individual cells and include quantitative data on hundreds of different parameters that enable predictions about how genes work and operate together.

“For my entire career, I’ve wanted to see what happens in cells when the function of an essential gene is eliminated,” said Iain Cheeseman, a senior author of the study and a member of Whitehead Institute. “Now, we can do that, not just for one gene but for every single gene that matters for a human cell dividing in a dish, and it’s enormously powerful. The resource we’ve created will benefit not just our own lab but labs around the world.”

Using an approach based on CRISPR proteins, MIT researchers have developed a new way to precisely control the amount of a particular protein that is produced in mammalian cells.

This technique could be used to finely tune the production of useful proteins, such as the monoclonal antibodies used to treat cancer and other diseases, or other aspects of cellular behavior. In their new study, which appears in Nature Communications, the researchers showed that this system can work in a variety of mammalian cells, with very consistent results.

“It’s a highly predictable system that we can design up front and then get the expected outcome,” says William C.W. Chen, a former MIT research scientist. “It’s a very tunable system and suitable for many different biomedical applications in different cell types.”

A team of researchers at Umeå University has discovered that an enzyme in human cells has probably evolved from an ancient single-celled organism. The enzyme’s unique properties mean that it could be used as a building block in the design of new enzymes, for example in processing wood raw materials. The discoveries are presented in Science Advances.

Life on Earth is divided into three groups of organisms: bacteria, archaea and eukaryotes, with humans belonging to the last group, the eukaryotes. One theory is that we evolved from archaea, which in turn may have evolved from bacteria.

Now, a team of researchers from the Department of Chemistry at Umeå University has discovered clear traces of an archaea (odinarchaeota) in an enzyme found in the nucleus of human cells. The human enzyme is called AK6 and has a variety of functions, such as energy metabolism, genome stabilization and programmed cell death.

The human genome has just over 20,000 genes coding for proteins. Yet, it produces at least ten times that many different non-coding RNA molecules, which can often take on more than one shape. At least some of this RNA structurome is functional in physiology or pathophysiology.

In an invited review for Nature Reviews Genetics, Danny Incarnato, a molecular geneticist from the University of Groningen (The Netherlands), and his colleague Robert C. Spitale from the University of Irvine in California (USA) describe ways to develop the, as yet, largely untapped potential of RNA structures.

RNA is perhaps best known as the intermediate between genome and protein synthesis: messenger RNA molecules copy the genetic code of a gene in the cell’s nucleus and transport it to the cytoplasm, where ribosomes translate the code into a protein. However, RNA is also a key regulator of almost every cellular process and the structures that are adopted by RNA molecules are thought to often be key to their functions.

Artificial intelligence has long been a hot topic: a computer algorithm “learns” by being taught by examples: What is “right” and what is “wrong.” Unlike a computer algorithm, the human brain works with neurons—cells of the brain. These are trained and pass on signals to other neurons. This complex network of neurons and the connecting pathways, the synapses, controls our thoughts and actions.

Biological signals are much more diverse when compared with those in conventional computers. For instance, neurons in a biological neural network communicate with ions, biomolecules and neurotransmitters. More specifically, neurons communicate either chemically—by emitting the messenger substances such as neurotransmitters—or via electrical impulses, so-called “action potentials” or “spikes”.

Artificial neurons are a current area of research. Here, the efficient communication between the biology and electronics requires the realization of artificial neurons that emulate realistically the function of their biological counterparts. This means artificial neurons capable of processing the diversity of signals that exist in biology. Until now, most artificial neurons only emulate their biological counterparts electrically, without taking into account the wet biological environment that consists of ions, biomolecules and neurotransmitters.

A paralyzed man who cannot speak or type was able to spell out over 1,000 words using a neuroprosthetic device that translates his brain waves into full sentences, US researchers said Tuesday.

“Anything is possible,” was one of the man’s favorite phrases to spell out, said the first author of a new study on the research, Sean Metzger of the University of California San Francisco (UCSF).

Continue reading “Brainwave-reading implant lets paralyzed man spell out 1,100 words” »

A new approach to stem cell therapy that uses antibodies instead of traditional immunosuppressant drugs robustly preserves cells in mouse brains and has potential to fast-track trials in humans, a Michigan Medicine study suggests.

For this study, researchers used monoclonal antibodies to suppress the immune system in mice and compared the results to traditional immunosuppression with the medications tacrolimus and mycophenolate mofetil. They tracked implanted human neural stem cell survival using luciferase, the protein that makes fireflies glow.

Results published in Clinical and Translational Medicine reveal that suppression with monoclonal antibodies enabled long-term survival of human stem cell transplants in mouse brains for at least six to eight months, while the cell grafts did not survive more than two weeks in most animals when using standard immunosuppressant drugs.

). At P7, Pten^flx/flx and Pten^flx/flxRaptor^flx/flx animals were co-injected into the dentate gyrus with a retrovirus encoding a fluorophore (GFP) with a downstream Cre, and a control retrovirus with just a fluorophore (mCherry) and no Cre (Figure 3A). Here, the GFP-expressing newborn granule neurons are KOs for their respective flox genes, while mCherry-expressing neurons serve as their in-tissue WT controls. To investigate the role of mTORC1 in development of Pten KO-mediated somal hypertrophy, we quantified soma size of retrovirally infected immunolabeled granule neurons at P28. We observed that Pten KO neurons had significantly greater soma size when compared with their WT control. This increase in soma size was completely rescued in Pten and Raptor double knockout (DKO) neurons (Table S1A and Figures 3B and 3D). We further examined the role of mTORC1 in aberrant migration of Pten KO granule neurons. The Pten KO neurons migrate significantly farther from the hilus along the GCL, when compared with their WT control. This farther migration was completely rescued in Pten and Raptor DKO neurons (Table S1B and Figures 3B and 3E). The dendritic spine density was also found to be significantly increased in Pten KO neurons. This increase in number of spines in middle molecular layer was reduced to WT density in Pten and Raptor DKO neurons (Table S1C and Figures 3C and 3F). Additionally, the decrease in spine head diameter seen in Pten KO neurons was rescued in Pten and Raptor DKO neurons (Table S1D). However, the increased spine length of Pten KO neurons persisted in the Pten and Raptor DKO neurons (Table S1E). These data suggest that Pten loss-mediated neuronal hypertrophy can be rescued by targeting Raptor to disrupt mTORC1.

To examine the role of mTORC1 in the Pten loss-mediated dendritic overgrowth of granule neurons, we reconstructed and quantified retrovirally infected immunolabeled Pten KO granule neurons, as well as Pten and Raptor DKO granule neurons at P28 (Figures 4A and 4B). We observed that Pten KO granule neurons had more elaborate dendritic arbor. Sholl analysis revealed that Pten KO neurons had an increased number of intersections, when compared with WT control neurons. This increase was completely rescued in Pten and Raptor DKO neurons (Table S1F and Figure 4C). The total dendritic length was also increased in Pten KO neurons, which was rescued in Pten and Raptor DKO neurons (Table S1G and Figure 4D). Further analysis revealed that Pten KO neurons have more primary dendrites protruding directly out of the soma, when compared with their WT control. This increase in number of primary dendrites was completely rescued in Pten and Raptor DKO neurons (Table S4A and Figure S2A).