Astrocytes are brain cells that, among other things, help neurons form active connections with each other. The exact mechanism behind this process has been a mystery. Scientists in Nicola Allen’s lab have begun to uncover more about these important cells. Allen and first author Isabella Farhy-Tselnicker discovered that astrocytes initiate communication between pairs of neurons by prompting specific changes in neurons through a protein called glypican 4. This protein influences both sending and receiving neurons, helping them make synaptic connections. It may be a target for better understanding neurodevelopmental disorders, such as autism, ADHD and schizophrenia, all of which may result at least partially from faulty communication between neurons. The work was published in Neuron on October 11, 2017.
“Busybody” protein may get on your nerves, but that’s a good thing
Sensory neurons regulate how we recognize touch and pain as well as body movement and position, but neuroscientists are only now beginning to unravel this circuitry. New research from Kuo-Fen Lee’s lab, co–first authored by Zhijiang Lee and Christopher Donnelly, and in collaboration with researchers at the University of Michigan, shows how a protein involved in many different signaling pathways plays a key role in pain signaling in the brain. This “busybody” protein, called p75, enhances the survival of proteins that support sensory neurons involved in transmitting pain signals. When p75 is removed, the survival-promoting signal of these proteins is reduced and the neurons that respond to this signal gradually degenerate. These findings could lead to new insights into neurological disorders, as well as spinal cord injuries and other traumas. The work was published on October 17, 2017, in Cell Reports.Read News Release
Every day, websites and apps crunch huge sets of information to find data points that resemble each other, such as products that are similar to past purchases. These tasks are called similarity searches, and performing them well—and fast—has been an ongoing challenge for computer scientists. Salk faculty Saket Navlakha and Charles Stevens, together with collaborator Sanjoy Dasgupta of UC San Diego, have shown that fruit fly brains, in their efforts to identify similar odors, may have found a better way to perform similarity searches. Current computer algorithms find similar items by reducing the amount of information associated with each item. Fly brains do the opposite, expanding the amount of information associated with each item, which allows them to better distinguish similar from dissimilar. When the researchers applied this approach of expanding rather than reducing information associated with data to three standard datasets, they found the fly method dramatically improved search performance. They reported their findings in Science on November 9, 2017.
Multifunctional protein contributes to blood cell development
Researchers in Martin Hetzer’s lab found a previously unknown role for a protein called nup98. In addition to helping control how certain molecules move in and out of a cell’s nucleus, nup98 helps direct the development of blood cells, enabling immature blood stem cells to differentiate into mature cell types. The team described their discovery in the December 21, 2017, issue of Genes & Development. Hetzer, first author Tobias Franks and collaborators found that when perturbed, this differentiation process can contribute to certain leukemias, making nup98 a potential target for new cancer therapies.Read News Release
Revealing the best-kept secrets of proteins
In the bustling setting of the cell, proteins encounter each other by the thousands. Despite the hubbub, each one manages to selectively interact with just the right partners thanks to specific contact regions on its surface. However, these regions have remained far more mysterious than might be expected, especially given decades of research into protein structure and function. Salk Professor Vicki Lundblad and co–first authors John Lubin and Timothy Tucey, now at Monash University, developed a new method to discover which surface contacts on proteins are critical for these cellular interactions. Their approach shows that essential new functions can be uncovered even for well-studied proteins, and has significant implications for therapeutic drug development, which depends heavily on how drugs physically interact with their cellular targets. The paper appeared in the early-access online version of Genetics on November 29, 2017.Read News Release
In the bustling setting of the cell, proteins encounter each other by the thousands. Despite the hubbub, each one manages to selectively interact with just the right partners thanks to specific contact regions on its surface. However, these regions have remained far more mysterious than might be expected, especially given decades of research into protein structure and function. Salk Professor Vicki Lundblad and co–first authors John Lubin and Timothy Tucey, now at Monash University, developed a new method to discover which surface contacts on proteins are critical for these cellular interactions. Their approach shows that essential new functions can be uncovered even for well-studied proteins, and has significant implications for therapeutic drug development, which depends heavily on how drugs physically interact with their cellular targets. The paper appeared in the early-access online version of Genetics on November 29, 2017.
When your spinal cord takes charge
We think the brain masterminds our actions, but a surprising amount of movement-related information is processed in the spinal cord. When we move, motor circuits in the spinal cord are constantly barraged by information from sensory receptors in the skin and muscles, information as varied as what our limbs are doing or what the ground underfoot feels like. This information is critical for actions like walking or standing still. Researchers in Martyn Goulding’s lab have solved a long-standing mystery about how spinal cords know when to pay attention to certain pieces of information and when to ignore them. Goulding, first author Stephanie Koch and others, in work published in Neuron on December 7, 2017, showed that specific neurons, called RORβ interneurons, inhibit the transmission of potentially disruptive sensory information during walking, allowing for a fluid gait.Read News Release
When you see brown spots on otherwise healthy green leaves, you may be witnessing a plant’s immune response as it tries to keep a bacterial infection from spreading. Some plants are more resistant to such infections than others. To explore why, Salk scientists Joanne Chory and co–first authors Marco Bürger and Björn Willige studied a plant protein called SOBER1, which had previously been probed in relation to infection, and discovered that, counterintuitively, SOBER1 rendered plants less resistant to infection. The work, which appeared in Nature Communications on December 29, 2017, sheds light on plant resistance generally and could lead to strategies to boost plants’ natural immunity or to better contain infections that threaten to destroy an entire agricultural crop.
A research team led by Juan Carlos Izpisua Belmonte, and including co–first authors Hsin-Kai (Ken) Liao and Fumiyuki Hatanaka, developed a new version of the CRISPR/Cas9 gene-editing tool, allowing them to activate genes without creating DNA breaks. This breakthrough could circumvent a major hurdle to using gene editing in the treatment of human diseases. Most CRISPR/Cas9 systems create double-stranded DNA breaks, but many researchers are opposed to creating these breaks in humans because they can cause additional health problems.
When the brain’s support cells aren’t so supportive
Early in human development, neurons make a flurry of connections that are then pruned back to fine-tune the brain. Assistant Professor Nicola Allen and UC San Diego graduate student Matthew Boisvert discovered that genes that get switched on to sever these early connections between neurons are later activated again in support cells called astrocytes. Named for their star-shaped appearance, astrocytes make up one-third to one-half of all brain cells and are critical for neuronal function. By comparing gene expression in astrocytes in adult and aged mouse brains, the team uncovered that a genetic program is reactivated as astrocytes age, causing neurons to lose connection with each other. The discovery, which appeared in Cell Reports on January 2, 2018, hints that astrocytes may be good therapeutic targets to prevent or reverse the effects of normal aging.Read News Release
Getting straight to the heart of the matter in stem cells
The process by which embryonic stem cells develop into heart cells is complex, involving the precisely timed activation of several molecular pathways and at least 200 genes. Now, Salk Professor Kathy Jones and first author Conchi Estarás, alongside their colleagues, have found a simpler way to go from stem cells to heart cells that involves turning off a single gene, called YAP. The work, which appeared in Genes & Development on December 21, 2017, offers scientists a streamlined method to arrive at functioning heart cells (cardiomyocytes) for both research and regenerative therapies.Read News Release
Alzheimer’s drug turns back clock in cellular powerhouse
The experimental drug J147, a synthetic, modified version of the curcumin molecule found in the spice turmeric, is almost ready for human trials. The lab of Dave Schubert developed J147 while looking for plant compounds that reverse cellular and molecular aging in the brain. Since then, the team has shown J147 reverses memory deficits, drives the production of new brain cells and slows or reverses Alzheimer’s disease progression in mice. Now Schubert, first author Josh Goldberg and their colleagues have figured out how J147 works: in a study published in Aging Cell on January 9, 2018, they reported that the drug binds to an enzyme called ATP synthase, which is found in our cells’ power-generating organelles (mitochondria). The team showed that, by manipulating ATP synthase activity, they could protect brain cells from multiple toxicities associated with aging. Unraveling J147’s mechanism of action is a critical step towards clinical trials in humans.Read News Release
Research led by Satchidananda Panda, with first author Gabriele Sulli, showed how to curb cancer cell growth by blocking the cells’ access to nutrients. The key is the circadian cycle, the intrinsic clock that exists in all living things and helps control when individual cells produce and use nutrients. The team focused on REV-ERBα and REV-ERBβ, proteins that are part of the clock’s machinery and modulate cells’ ability to synthesize fats and recycle materials.
- Taking on the Big FiveCancer is not like other diseases. Most conditions have external causes—bacteria, viruses, injury—but cancer comes from inside us. Cells go rogue, divide recklessly, invade other tissues and spread throughout the body. They do things normal cells cannot do.
- Dan Lewis – Intense ConnectionFew trustees have had a connection as intensely personal as new Board Chair Dan Lewis, who knows firsthand that cures, indeed, begin with Salk. Thanks to the research of Salk Professor Tony Hunter, the drug Gleevec was born. And thanks to Gleevec, Lewis survived leukemia.
- Jared SmithNeuroscientist and self-described history geek Jared Smith wants to boldly go where no one has gone before. “If this were the 1400s,” asks Smith, “and we were Europeans exploring the world, where is the new world?” For Smith and colleagues in Xin Jin’s lab, the answer is simple: the brain.