Epigenetic changes regulate gene expression, but what regulates epigenetics? 

All the cells in an organism have the exact same genetic sequence. What differs across cell types is their epigenetics, meticulously placed chemical tags that influence which genes are expressed in each cell. Mistakes or failures in epigenetic regulation can lead to severe developmental defects. This creates a puzzling question: If epigenetic changes regulate our genetics, what is regulating them?  Salk scientists, led by biochemist Julie Law, PhD, used plant cells to discover that a type of epigenetic tag called DNA methylation can be regulated by genetic mechanisms. Prior to this study, scientists understood only how DNA methylation could be initiated by other preexisting epigenetic modifications, which didn’t explain how novel methylation patterns could arise. The discovery that the DNA itself can instruct new methylation patterns is a major paradigm shift and helps explain how a cell can modify its epigenetics to grow, respond, and recover. The findings could inform future bioengineering strategies for altering methylation patterns to repair or enhance specific cell functions, with many potential applications in medicine and agriculture.  Read news release

Could a dietary supplement make the difference between life and death during illness?  

Why is it that two people can develop the same infection but have dramatically different disease trajectories? Salk scientist Janelle Ayres, PhD, and her colleagues discovered that the kidney plays a key role in filtering inflammatory molecules out of the body after an infection, and the amino acid methionine can improve that filtration. Dietary supplementation of methionine was enough to boost kidney performance in mice and protect against inflammation-related wasting, blood-brain barrier dysfunction, and death. The findings highlight how small dietary changes can lead to big impacts in disease outcomes and could support the use of methionine in future treatments for inflammatory conditions, especially in patients with kidney dysfunction.  “Our findings add to a growing body of evidence that common dietary elements can be used as medicine. By studying these basic protective mechanisms, we reveal surprising new ways to shift individuals that are fated to develop disease and die onto trajectories of health and survival. It may one day be possible for something as simple as a supplement with dinner to make the difference between life and death for a patient.”  JANELLE AYRES  Read news release

Could biochemical engineering tools reveal new insights into lung cancer?  

For cancer cells to grow and proliferate, they must be able to rapidly build and renew their outer membranes. These membrane structures are made of fatty molecules called lipids, but technical limitations have made it difficult to measure the dynamics of lipid metabolism. In a new study, Salk scientists, led by Christian Metallo, PhD, used biochemical engineering tools and principles to address this problem.  The team successfully repurposed a technique traditionally used to model glucose and mitochondrial metabolism to now measure changes in lipid flux in tumors. They collaborated with fellow Salk cancer researcher Reuben Shaw, PhD, to study lung cancer models, identifying specific changes in metabolism depending on the genetic mutations present in a tumor. This technology will now help them identify new therapeutic candidates to target lipid metabolism in cancer and other diseases.  “What’s really cool about this new technology is that Reuben and I asked these same questions with older technology years ago, so we were especially attuned to the improvements. The new model offers much more detail and is going to allow us to better identify, validate, and target therapeutic candidates in lipid metabolism, lung cancer, and beyond.”  CHRISTIAN METALLO 

How do brains stay stable, and when might a dose of flexibility be helpful? 

Young minds are easily molded. Each new experience rewires a child’s brain circuitry, adding and removing synaptic connections between neurons. These wiring patterns become more stable with age, but biology has left some wiggle room to ensure that adult brains can still adapt and refine their circuitry as needed.  Nicola Allen, PhD, and her team have now discovered a molecule that is critical for stabilizing brain circuits in adulthood: a protein called CCN1 secreted by star-shaped cells called astrocytes. Mouse studies showed that CCN1 coordinates the maturation of multiple cell types to reduce the plasticity of the adult brain, but removing it had the opposite effect. The CCN1 pathway could now be a prime target for new therapeutics designed to support learning and plasticity in people with conditions such as Alzheimer’s disease, depression, or PTSD, or to promote neural repair after injury or stroke.  Read news release

Genome-informed restoration could save our oceans and coastlines 

Seagrasses preserve our oceans and planet by absorbing carbon dioxide, calming rough waters, and offering a safe harbor for sea life. Unfortunately, these underwater meadows are under threat, and coastal restoration efforts to replant them often fail.  In the waters of San Diego’s Mission Bay, a new hybrid seagrass has started to grow. The hybrid is a cross between the shallow-water Zostera marina and its deeper-water cousin, Zostera pacifica, whose tolerance for low-light conditions is a favorable trait as coastal waters become increasingly murky. A research team at Salk and UC San Diego, led by plant biologist Todd Michael, PhD, used advanced genomic and transcriptomic technologies to investigate the hybrid seagrass and found that it possesses specific circadian clock genes, inherited from its deep-water relative, that help it tolerate low-light conditions. The scientists say this genomic profile could make the new hybrid seagrass a promising candidate for future “genomically informed” coastal restoration efforts in California and beyond.  “With these genomic resources, we can replace trial-and-error plantings, which fail in up to 60 percent of Zostera projects, with genomically informed restoration, selecting genome-environment-matched plants to markedly improve establishment and long-term success.”  TODD MICHAEL  Read news release