Lifeboat Foundation

The genetic information of an organism is stored within DNA. It contains the code for making other molecules that make all cells and organs of the body functional. Interestingly, only 1% of DNA makes up genes, of which proteins are produced via RNA intermediaries. There is much debate on the role of the remaining DNA, but different types of RNA are thought to be produced from it and direct the fate of the cell. Even though each cell of the body contains the same DNA, how they read and process DNA to make RNA can differ quite dramatically between single cells. This has especially been known for the transcriptome, which includes all RNA that are produced from genes, but not so much for other RNA.

“Genes have been the main focus of biological research for a long time,” says lead author of the study Haruka Ozaki. “We wanted to focus on what we call read coverage of single-cell RNA sequencing (scRNA-seq) data, which also includes RNA that are not products of genes. Although we can measure the amount of different RNA a single cell produces by scRNA-seq technologies, we wanted to come up with a new method that also visualizes specifically read coverage, because only then we can get a full picture of RNA biology and how it contributes to cell biology at the single-cell level.”

To achieve their goal, the researchers developed a new computational tool that they called Millefy uses existing scRNA-seq data to visualize read coverage of single cells as a heat map, illustrating differences between individual cells on a relative scale. The researchers first demonstrated the utility of Millefy in a well-established mouse embryonic stem cell model by showing heterogeneity of read coverage between developing cells. They then applied Millefy to cancer cells from patients with triple-negative breast cancer, a particularly aggressive type of breast cancer. Not only did Millefy show heterogeneity between cancer cells in general, but it revealed heterogeneity in a specific aspect of RNA biology that had previously been unknown.

Continue reading “Seeing is believing: Visualizing differences in RNA biology between single cells” »

Andrew Sinclair does not have anything to lose. He takes a number of drugs including the anti-diabetic medication metformin, given to him by his son David, the renowned Australian biologist and professor of genetics at Harvard Medical School, to combat the ill-effects of ageing.

David Sinclair says his father remains in good health, travelling, socialising and exercising with the energy of a man far younger than his 80 years.

David Sinclair will discuss why ageing should be classified as a disease at the Festival of Dangerous Ideas.

Continue reading “Flipping the switch on the ageing process” »

How did Viruses evolve?

The evolutionary history of viruses remains unclear. Some researchers hypothesize that viruses evolved from mobile genetic elements that gained the ability to move between cells. Other researchers postulate that viruses evolved from more complex organisms that lost the ability to replicate independently. Still others hypothesize that DNA viruses gave rise to the eukaryotic nucleus or that viruses predate all cellular life-forms. Reasonable arguments can be made for all of these hypotheses. It may be that viruses arose multiple times, via each of these mechanisms. It may be that viruses arose from a mechanism yet to be described. Continuing studies of viruses and their hosts may provide us with clearer answers.

Josie Golding, Ph.D., who is the epidemics lead at the Wellcome Trust, a research charity based in London, United Kingdom, did not participate in the study but comments on its significance.

She says the findings are “crucially important to bring an evidence-based view to the rumors that have been circulating about the origins of the virus (SARS-CoV-2) causing COVID-19.”

“[The authors] conclude that the virus is the product of natural evolution,” Goulding adds, “ending any speculation about deliberate genetic engineering.”

Stanford researchers have developed a technique that reprograms cells to use synthetic materials, provided by the scientists, to build artificial structures able to carry out functions inside the body.

“We turned cells into chemical engineers of a sort, that use materials we provide to construct functional polymers that change their behaviors in specific ways,” said Karl Deisseroth, professor of bioengineering and of psychiatry and behavioral sciences, who co-led the work.

In the March 20 edition of Science, the researchers explain how they developed genetically targeted chemical assembly, or GTCA, and used the new method to build artificial structures on mammalian brain cells and on neurons in the tiny worm called C. elegans. The structures were made using two different biocompatible materials, each with a different electronic property. One material was an insulator, the other a conductor.

A study by researchers at the National Cancer Institute (NCI), part of the National Institutes of Health, offers new insight into genetic alterations associated with osteosarcoma, the most common cancerous bone tumor of children and adolescents. The researchers found that more people with osteosarcoma carry harmful, or likely harmful, variants in known cancer-susceptibility genes than people without osteosarcoma. This finding has implications for genetic testing of children with osteosarcoma, as well as their families.

The study was published March 19, 2020, in JAMA Oncology.

“With this study, we wanted to find out how many people with osteosarcoma may have been at high risk for it because of their genetics,” said Lisa Mirabello, Ph.D., of NCI’s Division of Cancer Epidemiology and Genetics (DCEG), who led the research. “We not only learned that at least a quarter of the people in the study with osteosarcoma had a variant in a gene known to predispose someone to cancer, we also uncovered variants that had never before been associated with this cancer.”

Now, in an important new resource for the scientific community published today in Nature Biotechnology, researchers in the lab of Neville Sanjana, PhD, at the New York Genome Center and New York University have developed a new kind of CRISPR screen technology to target RNA.

The researchers capitalized on a recently characterized CRISPR enzyme called Cas13 that targets RNA instead of DNA. Using Cas13, they engineered an optimized platform for massively-parallel genetic screens at the RNA level in human cells. This screening technology can be used to understand many aspects of RNA regulation and to identify the function of non-coding RNAs, which are RNA molecules that are produced but do not code for proteins.

By targeting thousands of different sites in human RNA transcripts, the researchers developed a machine learning-based predictive model to expedite identification of the most effective Cas13 guide RNAs. The new technology is available to researchers through an interactive website and open-source toolbox to predict guide RNA efficiencies for custom RNA targets and provides pre-designed guide RNAs for all human protein-coding genes.

A new variation of the gene-editing technology CRISPR-Cas9 can correct mutations in the CFTR gene — the genetic cause of cystic fibrosis (CF) — in stem cells from CF patients, a study shows.

The new approach has the ability to correct mutations without the need to excise the affected region, the researchers said.

The study, “CRISPR-Based Adenine Editors Correct Nonsense Mutations in a Cystic Fibrosis Organoid Biobank,” was published in the journal Cell Stem Cell.

Scientists can now edit multiple sites in the genome at the same time to learn how different DNA stretches co-operate in health and disease.

CRISPR-based DNA editing has revolutionized the study of the human genome by allowing precise deletion of any human gene to glean insights into its function. But one feature remained challenging—the ability to simultaneously remove multiple genes or gene fragments in the same cell. Yet this type of genome surgery is key for scientists to understand how different parts of the genome work together in the contexts of both normal physiology and disease.

Now such a tool exists thanks to the teams of Benjamin Blencowe and Jason Moffat, both professors of molecular genetics at the Donnelly Centre for Cellular and Biomolecular Research. Dubbed ‘CHyMErA’, for Cas Hybrid for Multiplexed Editing and Screening Applications, the method can be applied to any type of mammalian cell to systematically target the DNA at multiple positions at the same time, as described in a study published in the journal Nature Biotechnology.