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IN THIS ISSUE

Nature Plants
03/2020

How plants sound the alarm about danger

One role of plant hormones is to perceive trouble—whether an insect attack, drought or intense heat or cold—and then signal to the rest of the plant to respond. Now, Professor Joseph Ecker, Salk co-first author Mark Zander and collaborators report new details about how plants respond to a hormone called jasmonic acid, or jasmonate. The findings reveal a complex communication network and could help members of Salk’s Harnessing Plants Initiative develop crops that are hardier and more able to withstand rapid climate change.

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eLife
04/2020

New insights into how genes control courtship and aggression

Fruit flies, like many animals, engage in a variety of courtship and fighting behaviors. Assistant Professor Kenta Asahina and co-first authors Kenichi Ishii and Margot Wohl have uncovered the molecular mechanisms by which two sex-determining genes affect fruit fly behavior. The male flies’ courtship and aggression behaviors, they showed, are mediated by two distinct genetic programs. The findings, both published in eLife, demonstrate the complexity of the link between sex and behavior.

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Cell Reports
10/2019

Circadian cycles can benefit our health

Professor Satchin Panda studies circadian clocks, the internal programs that mediate our daily biological rhythms and affect our health. In two recent papers, Panda and his team examined how the body sets these clocks, while a third paper reveals what these rhythms can mean for our well-being.

In the first paper, Panda and colleagues reported a novel technique for determining how neurons communicate, which was employed in mice to uncover details about how the brain responds to light signals received by the retina. In the second study, Panda, Salk first author Ludovic Mure and colleagues reported the discovery of three cell types in the eye that detect light and align the brain’s circadian rhythm to ambient light.

In the third paper, Panda, Salk first author Emily Manoogian and colleagues described their clinical study of eating schedules based on circadian rhythms. They found that a 10-hour time-restricted eating intervention, when combined with traditional medications, resulted in a variety of health benefits for participants with metabolic syndrome, including weight loss, reduced abdominal fat, lower blood pressure and cholesterol, and more stable blood sugar and insulin levels. This pilot study could lead to a new treatment option for patients who are at risk for developing life-altering and costly medical conditions such as diabetes.

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Cell,
Science
10/2019

Understanding early cell development

After an egg is fertilized, cells begin to divide and form a blastocyst, a two-layered cluster of cells. The way a blastocyst develops has implications for whether a pregnancy is successful, how organs form, and potentially even for diseases later in life, but studying blastocysts has been a challenge. Professor Juan Carlos Izpisua Belmonte and colleagues created mouse blastocyst-like structures, dubbed “blastoids,” that had the same structure as natural blastocysts, and offering a powerful new tool to advance research by circumventing the need for natural embryos.

The Izpisua Belmonte lab also wanted to study a critical milestone in development after the formation of the blastocyst: gastrulation. This stage occurs when an embryo transforms into a three-layered structure, from which all future tissues and organs will be derived. Izpisua Belmonte led an international team to uncover new insights into gastrulation by creating a method enabling primate embryos to grow in the laboratory longer than ever before. The research, while done in nonhuman primate cells, could potentially inform approaches to regenerative medicines.

Read October 31, 2019 News Release

Read October 17, 2019 News Release
Cell Reports
12/2019

Diabetes drug has unexpected, broad implications for healthy aging

Metformin is the most commonly prescribed type 2 diabetes drug, yet scientists still do not fully know how it works to control blood sugar levels. Professor Reuben Shaw, director of Salk’s NCI-designated Cancer Center, and collaborators have used a novel technology to investigate why it functions so well. The findings, which identified a surprising number of biochemical “switches” for various cellular processes, could also explain why metformin has been shown in recent studies to extend health span and life span.

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eLife
11/2019

Alzheimer’s drug candidates reverse broader aging, study shows

Scientists from the lab of Professor David Schubert, including first author Antonio Currais and co-corresponding author Pamela Maher, have shown how the Alzheimer’s drug candidates CMS121 and J147 can slow aging in healthy older mice, blocking the damage to brain cells that normally occurs during aging and restoring the levels of specific molecules to those seen in younger brains. The research points out a new pathway that links normal aging to Alzheimer’s disease.

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Biological Psychiatry
10/2019

Altered potassium levels in neurons may cause mood swings in bipolar disorder

People with bipolar disorder experience dramatic shifts in mood, oscillating between often debilitating periods of mania and depression. Now, a sweeping new set of findings by Professor and Salk President Rusty Gage, first author Shani Stern and colleagues has revealed previously unknown details about why some neurons in bipolar patients swing between being over- or underexcited. In two recent papers, the team used experimental and computational techniques to describe variations in potassium and sodium levels in brain cells derived from people with bipolar disorder, which may help to further explain why one-third of patients respond to lithium and the rest do not.

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Nature Metabolism
12/2019

Mitochondria are the “canary in the coal mine” for cellular stress

Mitochondria, tiny structures present in most cells, are known for their energy-generating machinery. Professor Gerald Shadel, first author Zheng Wu and colleagues have discovered a new function of mitochondria: they set off molecular alarms when cells are exposed to stress or to chemicals that can damage DNA, such as chemotherapy. The results could lead to new cancer treatments that prevent tumors from becoming resistant to chemotherapy.

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Science
11/2019

Brain biomarker predicts compulsive drinking

Although alcohol use is ubiquitous in modern society, only a portion of individuals develop alcohol use disorders or addiction. Yet, scientists have not understood why some individuals are prone to developing drinking problems, while others are not. Professor Kay Tye and colleagues have discovered a brain circuit that controls alcohol drinking behavior in mice. The findings suggest a biomarker for predicting the development of compulsive drinking and may pave the way for a better understanding of human binge drinking and addiction.

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Nature Communications
10/2019

Microproteins have major implications for human disease

Roughly 25,000 genes code for biologically relevant proteins, most of which are large chains of 300 or more linked amino acids. But, increasingly, “microproteins,” with fewer than 100 amino acids, are being found to have important roles in health and disease.

In a study published in October, Professor Alan Saghatelian, co-corresponding author Uri Manor, first author Qian Chu and colleagues showed that the microprotein PIGBOS contributes to mitigating cell stress. In the second study, published in December, Saghatelian and first author Thomas Martinez identified over 2,000 new, small genes that may encode for microproteins—expanding the number of human genes by 10 percent. Both publications provide a better understanding of human biology that may eventually have implications for diseases ranging from cancer to diabetes.

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Cell
01/2020

A road map for ovarian health and aging

Izpisua Belmonte’s lab published additional work uncovering how ovaries age in nonhuman primates in unprecedented detail. This road map reveals several genes that could be used as biomarkers and could point to therapeutic targets for diagnosing and treating female infertility and age-associated ovarian diseases, such as ovarian cancer, in humans.

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Frontiers in Physiology
02/2020

Mysterious tuft cells found to play role in pancreatitis

The function of tuft cells—cells sensitive to chemical changes—in the pancreas has largely remained a mystery. Now, Professor Geoffrey Wahl, co-first authors Kathleen DelGiorno and Razia Naeem, and colleagues have uncovered how tuft cells form during pancreatic inflammation as well as their surprising role in immunity, using mouse models of pancreatitis. The findings could lead to the development of new biomarkers to test for pancreatitis and pancreatic cancer.

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Cell
02/2020

Eat less, live longer

If you want to reduce levels of inflammation throughout your body, delay the onset of age-related diseases and live longer—eat less food. That’s the conclusion of a new study led by a collaborative group of scientists, including Salk Professor Juan Carlos Izpisua Belmonte, that provides the most detailed report to date of the cellular effects of a calorie-restricted diet in rats. While the benefits of caloric restriction have long been known, the new results show how this restriction can protect against aging in cellular pathways.

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Cell Stem Cell
01/2020

Team links rapid brain growth in autism to DNA damage

Research into the developing brain, led by Professor and Salk President Rusty Gage, first author Meiyan Wang and colleagues, revealed a unique pattern of DNA damage that arises in brain cells derived from individuals with a macrocephalic form of autism spectrum disorder (ASD). They found that cells from people with this type of ASD not only proliferate more, but also naturally experience more replication stress, spurring DNA damage. The observation helps explain what might go awry in the brain during cell division and development to cause the disorder.

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Science
01/2020

Advances in imaging technique and new insight into how HIV drugs work at atomic level

Assistant Professor Dmitry Lyumkis’ team uses and optimizes an advanced imaging technique called cryo-electron microscopy (cryo-EM) to visualize large protein complexes within cells and to uncover how these structures work. In the fall, Lyumkis and Philip Baldwin co-authored a study that provides a foundation for quantitatively determining how differences in viewing angles affect the resulting 3D structures of proteins. Then, in January, Lyumkis, Salk co-first author Dario Passos and colleagues reported on how a powerful class of HIV drugs binds to a key piece of HIV machinery. By resolving this complex in 3D for the first time while different drugs were attached, the researchers discovered structural reasons for why these therapies are so potent.

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Protein & Cell
01/2020

Drug combo reverses arthritis in rats

People with osteoarthritis, or “wear and tear” arthritis, have limited treatment options: pain relievers or joint replacement surgery. Research co-led by Professor Juan Carlos Izpisua Belmonte and Salk co-first authors Paloma Martinez-Redondo and Isabel Guillen-Guillen, has discovered that a powerful combination of two experimental drugs reverses the cellular and molecular signs of osteoarthritis in rats as well as in isolated human cartilage cells.

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Journal of Biological Chemistry
05/2020

Experimental drug boosts levels of good fats

Professor Alan Saghatelian, first author Meriç Erikci Ertunc and a collaborative team of scientists have identified two genes that can regulate levels of healthy fats called FAHFAs, in mice. Because FAHFAs decrease inflammation and increase insulin sensitivity, a better understanding of the activity of their regulatory genes may eventually lead to therapies for people with diabetes and inflammation. They found that the loss of the genes led to higher-than-normal levels of the beneficial FAHFAs, while blocking the genes’ activity with an experimental drug also increased FAHFA levels.

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