Salk scientists discover how early life experiences influence DNA in the adult brain

Salk Institute scientists report in the journal Science that the type of mothering a female mouse provides her pups actually changes their DNA. The work lends support to studies about how childhood environments affect brain development in humans and could provide insights into neuropsychiatric disorders such as depression and schizophrenia.

According to Salk, most cells in the mammalian brain undergo changes to their DNA that make each neuron slightly different from its neighbor. Some of these changes are caused by “jumping” genes—known as long interspersed nuclear elements (LINEs)—that move from one spot in the genome to another. In 2005, Salk scientist Rusty Gage and his team discovered that a jumping gene called L1, which was already known to copy and paste itself into new places in the genome, could jump in developing neuronal brain cells.

As reported in Science, the team recently discovered a correlation between maternal care and L1 copy number: Mice with attentive mothers had fewer copies of the jumping gene L1, and those with neglectful mothers had more L1 copies, and thus more genetic diversity in their brains. Further research showed that mice with neglectful mothers had noticeably fewer methylated L1 genes than those with attentive mothers, suggesting that methylation is the mechanism responsible for the mobility of the L1 gene.

Palgrave Communications: “Will the Sustainable Development Goals be fulfilled? Assessing present and future global poverty”

Palgrave Communications, an affiliate of Nature, has published an article by the Converting Geospatial Observations into Socioeconomic Data project lead Jesús Crespo Cuaresma and his colleagues. The article focuses on their efforts to assess the potential future trends in poverty as a means of monitoring progress toward the fulfillment of the Sustainable Development Goals (SDGs) set forth by the United Nations. Crespo Cuaresma et al. have developed an econometric tool that provides a methodological framework to carry out projections of poverty rates worldwide and aims at assessing absolute poverty changes at the global level under different scenarios. The framework builds upon the combination of new estimates of the worldwide distribution of income and macroeconomic projections of population by age and educational attainment level, as well as income per capita, which have been recently developed in the context of climate change research.

The research is being undertaken in conjunction with the World Data Lab (WDL), an economist-founded organization dedicated to deploying new methods in data collection, data curation and dissemination, laying the groundwork to advance social and economic research on poverty in the most underdeveloped regions worldwide. Included in these efforts is the Converting Geospatial Observations project, which NOMIS is supporting. The project aims to develop the first-ever sub-national income model for Kenya. Jesús Crespo Cuaresma is head of the Institute of Macroeconomics at the Vienna University of Economics and Business.

Jacob Corn named Professor of Genome Biology at ETH Zurich

Jacob Corn has been appointed Professor of Genome Biology at ETH Zurich. Corn is the founding scientific director of the Innovative Genomics Institute and adjunct assistant professor at the University of California, Berkeley. His research aims to bring about the end of genetic disease through the development and application of next-generation genome editing technologies — improving human health through the fundamental understanding of disease mechanisms.

Corn’s experience extends to therapeutic areas that include infectious disease, neurobiology and oncology, and his work has redefined our understanding of DNA replication. He computationally designed protein inhibitors from scratch and discovered biological mechanisms for challenging therapeutic targets.

The key objective of the ETH professorship, which is funded by NOMIS in cooperation with the Lotte und Adolf Hotz-Sprenger Stiftung, is to study the functional elements encoded in complex genomes through comparative analysis, seeking to deepen our understanding of how the genetic variation in the human population is related to disease susceptibility.

Corn is exploring processes that detect and repair damage to DNA, using these findings to repair, switch on or off, or replace genes in the genome at a defined position. This knowledge is important for both therapeutic use as well as basic and applied research.

Christian Haass is awarded world’s top brain research prize

NOMIS board member Christian Haass and three other neuroscientists — Bart De Strooper, Michel Goedert and John Hardy — are the recipients of the 2018 Brain Prize for their groundbreaking research on the genetic and molecular basis of Alzheimer’s disease. The research pioneered by these four European scientists has revolutionized our understanding of the changes in the brain that lead to Alzheimer’s disease and related types of dementia.

When Haass, professor at Ludwig-Maximilians-University of Munich and at the German Center for Neurodegenerative Diseases, started to work on Alzheimer’s disease in 1990, very little was known about the cellular mechanisms involved in this disease. He focused on the generation and metabolism of amyloid, the major component of the disease that signifies plaques. Haass hypothesized that amyloid production may be normal and not necessarily part of a pathological process, which at the time was the widely accepted general opinion in the field. This pivotal finding was highly significant and has since led to the development of therapies to lower amyloid production in patients. Working with Hardy, Haass has demonstrated how amyloid is generated and how genetic mutations seen in families with very aggressive and rare forms of Alzheimer’s affect its production.

Most recently, Haass has generated mouse models to investigate inflammation in neurodegenerative disorders, which according to his findings may at least initially play a protective role. He found that genetic mutations alter the function of special immune cells called microglia in the brain that can lead to Alzheimer’s disease. This has stimulated a completely new approach to designing possible new therapies by modulating the activity of microglia.

The Brain Prize, awarded by the Lundbeck Foundation in Denmark, is worth one million euros. Awarded annually, it recognizes one or more international scientists who have distinguished themselves by an outstanding contribution to neuroscience.

SRF: “The fight against forgetting”

NOMIS Distinguished Scientist Tony Wyss-Coray appeared on the Swiss television program, Einstein, which aired on Feb. 15, 2018. The story, “Kampf gegen das Vergessen” (“The fight against forgetting”), addresses the crippling effects of Alzheimer’s disease and highlights Wyss-Coray’s promising research in this direction. Professor of neurology and neurological sciences at Stanford University, Wyss-Coray’s groundbreaking findings suggest that the plasma in our blood directly influences aging. His most recent studies have shown that circulatory factors can modulate neurogenesis, neuroimmunity and cognitive function in mice and that blood-derived factors from young mice or humans can rejuvenate the aging mouse brain.

NOMIS is supporting Wyss-Coray’s continued research into identifying the circulatory factors that influence aging and using those factors to rejuvenate the aging or degenerated brain.

Einstein is a weekly Schweizer Radio und Fernsehen (SRF) newsmagazine.

Salk Institute: “Alzheimer’s drug turns back clock in powerhouse of cell”

Salk researchers have identified the molecular target of J147. The experimental drug is something of a modern elixir of life; it’s been shown to treat Alzheimer’s disease and reverse aging in mice and is almost ready for clinical trials in humans. Now, Salk scientists have solved the puzzle of what, exactly, J147 does. In a paper published January 7, 2018, in the journal Aging Cell, they report that the drug binds to a protein found in mitochondria, the energy-generating powerhouses of cells. In turn, they showed, it makes aging cells, mice and flies appear more youthful.

“This really glues together everything we know about J147 in terms of the link between aging and Alzheimer’s,” says Dave Schubert, head of Salk’s Cellular Neurobiology Laboratory and the senior author on the new paper. “Finding the target of J147 was also absolutely critical in terms of moving forward with clinical trials.”

Schubert’s group developed J147 in 2011, after screening for compounds from plants with an ability to reverse the cellular and molecular signs of aging in the brain. J147 is a modified version of a molecule (curcumin) found in the curry spice turmeric. In the years since, the researchers have shown that the compound reverses memory deficits, potentiates the production of new brain cells, and slows or reverses Alzheimer’s progression in mice. However, they didn’t know how J147 worked at the molecular level.

In the new work, led by Schubert and Salk Research Associate Josh Goldberg, the team used several approaches to home in on what J147 is doing. They identified the molecular target of J147 as a mitochondrial protein called ATP synthase that helps generate ATP—the cell’s energy currency—within mitochondria. They showed that by manipulating its activity, they could protect neuronal cells from multiple toxicities associated with the aging brain. Moreover, ATP synthase has already been shown to control aging in C. elegans worms and flies.

The Salk Institute has been a NOMIS partner since 2008.

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Aging Cell
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