A new combined method for gene editing may finally give scientists a tool fine enough to probe life’s most nuanced processes. What combinations of mutations help cancer cells survive? Which cells in the brain are involved in the onset of Alzheimer’s disease? How do immune cells conduct their convoluted decision- making processes? Researchers at the Weizmann Institute of Science in Rehovot have now combined two powerful research tools – CRISPR gene editing and single- cell genomic profiling – in a method that may finally help us get answers to these questions and many more.
The new technology enables researchers to manipulate gene functions within single cells, and understand the results of each change in extremely high resolution. A single experiment with this method, according to the scientists, may be equal to thousands of experiments conducted using previous approaches, and it may advance the field of genetic engineering for medical applications.
The gene-editing technique CRISPR is already transforming biology research around the world, and its clinical use in humans is just around the corner. CRISPR was first discovered in bacteria as a primitive acquired immune system, which cuts and pastes viral DNA into their own genomes to fight viruses. In recent years, this bacterial system has been adopted by researchers to snip out or insert nearly any gene in any organism or cell, quickly and efficiently.
“But CRISPR, on its own, is a blunt research tool, since we often have trouble observing or understanding the outcome of this genomic editing,” said immunology Prof. Ido Amit, who led the study.
“Most studies so far have looked for black-or-white types of effects,” added Dr. Diego Jaitin, of Amit’s lab group, “but the majority of processes in the body are complex and even chaotic.” The team’s findings have been published in Cell.
Amit and colleagues have been developing the second arm of the new method – single-cell RNA sequencing, a rapidly advancing field that is making an impact on many areas of research and biotechnology. By sequencing the messenger RNA molecules in each individual cell – messages that indicate cellular activity – the researchers are able to uncover the molecular makeup of each cell, and to discern a nuanced range of cell identities and functions in a given cell population.
“It is a new molecular microscope,” says Amit.
Thousands of cells from a particular tissue in the body can be sequenced at once in his lab, uncovering variation in cell identities and functions. This method has been used to understand everything from the effects of fetal brain development, to how common immune cells function differently in the various tissues of our body, including their involvement in cancer or neurodegeneration. But single-cell sequencing has mostly been an observatory tool, providing a snapshot of a given tissue sample.
Combing CRISPR with the fine resolution of single- cell RNA sequencing can enable researchers to actively tinker with the genes in cells, and then to understand their functions within numerous cell types in a variety of situations. The challenge was to adapt the CRISPR gene editing technology so it could be used in combination with single-cell sequencing.
“The advent of CRISPR presented a true leap in the ability to understand and start editing immune circuits,” concluded Amit. “We are hoping that our approach will be the next leap forward, providing, among other things, the ability to engineer immune cells for immunotherapy.”
NUTS TO YOU FOR IMPROVED HEALTH
People who eat at least 20 grams of nuts per day have a lower risk of heart disease, cancer and other diseases. The analysis of all current studies on nut consumption and disease risk has revealed a handful of nuts can cut people’s risk of coronary heart disease by nearly 30%, of cancer by 15% and of premature death by 22%.
This daily consumption of nuts was also associated with a reduced risk of dying from respiratory disease by about a half, and diabetes by nearly 40%, although the researchers note that there is less data about these diseases in relation to nut consumption. The study, led by researchers from Imperial College London and the Norwegian University of Science and Technology, was recently published in the journal BMC Medicine.
The meta-analysis included 29 published studies from around the world that involved up to 819,000 participants, including more than 12,000 cases of coronary heart disease, 9,000 cases of stroke, 18,000 cases of cardiovascular disease and cancer, and more than 85,000 deaths.
While there was some variation between the populations that were studied, such as between men and women, people living in different regions or people with different risk factors, the researchers found that nut consumption was associated with a reduction in disease risk across most of them.
Study co-author Dagfinn Aune said, “We found a consistent reduction in risk across many different diseases, which is a strong indication that there is a real underlying relationship between nut consumption and different health outcomes. It’s quite a substantial effect for such a small amount of food.”
The study included all kinds of tree nuts, such as hazel nuts and walnuts, as well as peanuts – which are actually legumes. The results were in general similar whether total nut intake, tree nuts or peanuts were analyzed. Nuts and peanuts are high in fiber, magnesium, and polyunsaturated fats – nutrients that are beneficial for cutting cardiovascular disease risk and can reduce cholesterol levels. Some nuts, particularly walnuts and pecan nuts are also high in antioxidants, which can fight oxidative stress and possibly reduce cancer risk.
Even though nuts are quite high in fat, they are also high in fiber and protein, and there is some evidence that suggests nuts might actually reduce your risk of obesity over time. But don’t exaggerate by eating a whole bag daily; nuts are fattening, too.