LA JOLLA—Spinal cord nerve cells branching through the body resemble trees with limbs fanning out in every direction. But this image can also be used to tell the story of how these neurons, their jobs becoming more specialized over time, arose through developmental and evolutionary history. Salk researchers have, for the first time, traced the development of spinal cord neurons using genetic signatures and revealed how different subtypes of the cells may have evolved and ultimately function to regulate our body movements.
LA JOLLA—The ability to grow the cells of one species within an organism of a different species offers scientists a powerful tool for research and medicine. It’s an approach that could advance our understanding of early human development, disease onset and progression and aging; provide innovative platforms for drug evaluation; and address the critical need for transplantable organs. Yet developing such capabilities has been a formidable challenge.
LA JOLLA—Wolffia, also known as duckweed, is the fastest-growing plant known, but the genetics underlying this strange little plant’s success have long been a mystery to scientists. Now, thanks to advances in genome sequencing, researchers are learning what makes this plant unique—and, in the process, discovering some fundamental principles of plant biology and growth.
LA JOLLA—Lithium is considered the gold standard for treating bipolar disorder (BD), but nearly 70 percent of people with BD don’t respond to it. This leaves them at risk for debilitating, potentially life-threatening mood swings. Researchers at the Salk Institute have found that the culprit may lie in gene activity—or lack of it.
LA JOLLA and PALO ALTO, Calif.—The Salk Institute and BridgeBio Pharma, Inc. (Nasdaq: BBIO) today announced a three-year collaboration agreement formed to advance cutting-edge academic discoveries in genetically driven diseases toward therapeutic applications. Under the partnership, BridgeBio will help fund research programs from Salk’s world-renowned innovative cancer research, with the eventual goal of developing new therapeutics for patients in need.
LA JOLLA—The diabetes drug metformin—derived from a lilac plant that’s been used medicinally for more than a thousand years—has been prescribed to hundreds of millions of people worldwide as the frontline treatment for type 2 diabetes. Yet scientists don’t fully understand how the drug is so effective at controlling blood glucose.
LA JOLLA—In research that aims to illuminate the causes of human developmental disorders, Salk scientists have generated 168 new maps of chemical marks on strands of DNA—called methylation—in developing mice.
LA JOLLA—The human immune system is a finely-tuned machine, balancing when to release a cellular army to deal with pathogens, with when to rein in that army, stopping an onslaught from attacking the body itself. Now, Salk researchers have discovered a way to control regulatory T cells, immune cells that act as a cease-fire signal, telling the immune system when to stand down.
LA JOLLA—Chronic liver disease represents a major global public health problem affecting an estimated 844 million people, according to the World Health Organization. It is among the top causes of mortality in Australia, the UK and the United States. At the same time, it is both difficult to manage and there is no FDA-approved anti-fibrotic liver therapy. The microbiome—a complex collection of microbes that inhabit the gut—may be an unexpected indictor of health. Now, a collaborative team of Salk Institute and UC San Diego scientists have created a novel microbiome-based diagnostic tool that, with the accuracy of the best physicians, quickly and inexpensively identifies liver fibrosis and cirrhosis over 90 percent of the time in human patients.
LA JOLLA—Many cancer medications fail to effectively target the most commonly mutated cancer genes in humans, called RAS. Now, Salk Professor Geoffrey Wahl and a team of scientists have uncovered details of how normal RAS interacts with mutated RAS and other proteins in living cells for the first time. The findings, published in The Proceedings of the National Academy of Sciences on May 18, 2020, could aid in the development of better RAS-targeted cancer therapeutics.
LA JOLLA—Mitochondria, tiny structures present in most cells, are known for their energy-generating machinery. Now, Salk researchers have discovered a new function of mitochondria: they set off molecular alarms when cells are exposed to stress or chemicals that can damage DNA, such as chemotherapy. The results, published online in Nature Metabolism on December 9, 2019, could lead to new cancer treatments that prevent tumors from becoming resistant to chemotherapy.
LA JOLLA—While scientists know of about 25,000 genes that code for biologically important proteins, additional, smaller genes hiding in our DNA may be just as important. But these tiny lines of genetic code have proven tough to track down.
LA JOLLA—Although graduating from school, a first job and marriage can be important events in life, some of the most significant events happen far earlier: in the first few days after a sperm fertilizes an egg and the cell begins to divide.
LA JOLLA—Breast cancer is one of the most prevalent cancers, and some forms rank among the most difficult to treat. Its various types and involvement of many different cells makes targeting such tumors difficult. Now, Salk Institute researchers have used a state-of-the-art technology to profile each cell during normal breast development in order to understand what goes wrong in cancer.
LA JOLLA—In 2017, Salk scientists reported that tilting a frozen protein sample as it sat under an electron microscope was an effective approach to acquiring better information about its structure and helping researchers understand a host of diseases ranging from HIV to cancer. Now, they have developed a mathematical framework that underlies some of those initial observations.
LA JOLLA—The brain’s prefrontal cortex, which gives us our ability to solve problems and plan ahead, contains billions of cells. But understanding the large diversity of cell types in this critical region, each with unique genetic and molecular properties, has been challenging.
LA JOLLA—The ability to edit genes in living organisms offers the opportunity to treat a plethora of inherited diseases. However, many types of gene-editing tools are unable to target critical areas of DNA, and creating such a technology has been difficult as living tissue contains diverse types of cells.
LA JOLLA—In the nucleus of every living cell, long strands of DNA are tightly folded into compact chromosomes. Now, thanks to a new computational approach developed at the Salk Institute, researchers can use the architecture of these chromosome folds to differentiate between types of cells. The information about each cell’s chromosome structure will give scientists a better understanding of how interactions between different regions of DNA play a role in health and disease. The study was published in the Proceedings of the National Academy of Sciences the week of July 8, 2019.
LA JOLLA—The Salk Institute announced that Helmsley-Salk Fellow Patrick Hsu has been named to MIT Technology Review’s prestigious annual list of Innovators Under 35. Every year, the media company recognizes a list of exceptionally talented technologists whose work has great potential to transform the world.
LA JOLLA—What makes us human, and where does this mysterious property of “humanness” come from? Humans are genetically similar to chimpanzees and bonobos, yet there exist obvious behavioral and cognitive differences. Now, researchers from the Salk Institute, in collaboration with researchers from the anthropology department at UC San Diego, have developed a strategy to more easily study the early development of human neurons compared with the neurons of nonhuman primates. The study, which appeared in eLife on February 7, 2019, offers scientists a novel tool for fundamental brain research.
LA JOLLA—We’ve all heard the expression: “what doesn’t kill you makes you stronger.” Now, research led by a Salk Institute scientist suggests why, at a cellular level, this might be true. The team reports that brief exposures to stressors can be beneficial by prompting the cell to trigger sustained production of antioxidants, molecules that help get rid of toxic cellular buildup related to normal metabolism.
LA JOLLA—One reason we’re supposed to eat a variety of colorful fruits and vegetables is because they contain nutritious compounds called antioxidants. These molecules counteract the damage to our bodies from harmful products of normal cells called reactive oxygen species (ROS).
LA JOLLA—Most people have heard of the CRISPR/Cas9 gene-editing technology, which acts as targeted molecular scissors to cut and replace disease-causing genes with healthy ones. But DNA is only part of the story; many genetic diseases are caused by problems with RNA, a working copy of DNA that is translated into proteins.
LA JOLLA—Is it better to do a task quickly and make mistakes, or to do it slowly but perfectly? When it comes to deciding how to fix breaks in DNA, cells face the same choice between two major repair pathways. The decision matters, because the wrong choice could cause even more DNA damage and lead to cancer.
LA JOLLA—Scientists have, for the first time, corrected a disease-causing mutation in early stage human embryos with gene editing. The technique, which uses the CRISPR-Cas9 system, corrected the mutation for a heart condition at the earliest stage of embryonic development so that the defect would not be passed on to future generations.
LA JOLLA—Stretched out, the DNA from all the cells in our body would reach Pluto. So how does each tiny cell pack a two-meter length of DNA into its nucleus, which is just one-thousandth of a millimeter across?
LA JOLLA—(May 4, 2017) Salk Institute scientists have developed a novel technology to correct disease-causing aberrations in the chemical tags on DNA that affect how genes are expressed. These types of chemical modifications, collectively referred to as epigenetics or the epigenome, are increasingly being considered as important as the genomic sequence itself in development and disease.
LA JOLLA—Salk scientists and collaborators have shed light on a longstanding question about what leads to variation in stem cells by comparing induced pluripotent stem cells (iPSCs) derived from identical twins. Even iPSCs made from the cells of twins, they found, have important differences, suggesting that not all variation between iPSC lines is rooted in genetics, since the twins have identical genes.
LA JOLLA—When scientists talk about laboratory stem cells being totipotent or pluripotent, they mean that the cells have the potential, like an embryo, to develop into any type of tissue in the body. What totipotent stem cells can do that pluripotent ones can’t do, however, is develop into tissues that support the embryo, like the placenta. These are called extra-embryonic tissues, and are vital in development and healthy growth.
LA JOLLA—FedEx, UPS, DHL—when it comes to sending packages, choices abound. But the most important delivery service you may not have heard of? mRNA. That’s short for messenger RNA, which is how your DNA sends blueprints to the protein-assembly factories of your cells. When a protein is faulty, delivering synthetic mRNA to cells could trigger production of a functional version. And that’s a message people with a variety of genetic diseases want to hear.
LA JOLLA—Most of us would be lost without Google maps or similar route-guidance technologies. And when those mapping tools include additional data about traffic or weather, we can navigate even more effectively. For scientists who navigate the mammalian genome to better understand genetic causes of disease, combining various types of data sets makes finding their way easier, too.
LA JOLLA—We all know how hard it is to find something small like a dropped contact lens that blends into the background. It’s similarly tough for biologists to find tiny proteins against the complex background of the cell. But, increasingly, scientists are learning that such microproteins, which are overlooked by traditional detection methods, also have important biological roles to play.
LA JOLLA—We put things into a container to keep them organized and safe. In cells, the nucleus has a similar role: keeping DNA protected and intact within an enveloping membrane. But a new study by Salk Institute scientists, detailed in the November 2 issue of Genes & Development, reveals that this cellular container acts on its contents to influence gene expression.
LA JOLLA—Mitochondria, the power generators in our cells, are essential for life. When they are under attack—from poisons, environmental stress or genetic mutations—cells wrench these power stations apart, strip out the damaged pieces and reassemble them into usable mitochondria.
LA JOLLA–Scientists have discovered a previously unknown wellspring of genetic diversity in humans, chimps and most other primates. This diversity arises from a new component of itinerant sections of genetic code known as jumping genes.
LA JOLLA–Healthy brain, muscle, eye and heart cells would improve the lives of tens of thousands of people around the world with debilitating mitochondrial diseases. Now, researchers at the Salk Institute have gotten one step closer to making such cures a reality: they’ve turned cells from patients into healthy, mutation-free stem cells that can then become any cell type. The new approach is described July 15, 2015 in Nature.
LA JOLLA–Mice that have a genetic version of mitochondrial disease can easily be mistaken for much older animals by the time they are nine months old: they have thinning grey hair, osteoporosis, poor hearing, infertility, heart problems and have lost weight. Despite having this disease at birth, these mice have a “secret weapon” in their youth that staves off signs of aging for a time.
LA JOLLA–For thousands of women around the globe carrying a mitochondrial disease, having a healthy child can be a gamble. This set of diseases affect mitochondria, tiny powerhouses that generate energy in the body’s cells and are passed exclusively from mother to child.