New Method Tracks How Brain Cells Age

Fluorescence light micrograph of neurons derived from induced pluripotent stem cells. (IKELOS GmbH/Dr. Christopher B. Jackson/Science Photo Library)

Hospital nurseries routinely place soft bands around the tiny wrists of newborns that hold important identifying information such as name, sex, mother, and birth date. Researchers at Rockefeller University are taking the same approach with newborn brain cells—but these neonates will keep their ID tags for life, so that scientists can track how they grow and mature, as a means for better understanding the brain’s aging process. As described in a September 28, 2023 paper in Cell, the new method developed by Rockefeller geneticist Junyue Cao, PhD, and his colleagues is called TrackerSci (pronounced “sky”). This low-cost, high-throughput approach has already revealed that while newborn cells continue to be produced through life, the kinds of cells being produced vary greatly in different ages. This groundbreaking work, led by co-first authors grad students Ziyu Lu and Melissa Zhang from Cao’s lab, promises to influence not only the study of the brain but also broader aspects of aging and disease across the human body. The open-access Cell article is titled “Tracking Cell-Type-Specific Temporal Dynamics in Human and Mouse Brains.”

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UCLA-Led Team Develops Key Improvement to Nobel Prize-Winning Technology of Cryo-Electron Microscopy (Cryo-EM); Modification Enables High-Quality Images of Smaller Proteins

An electron microscope image of scaffolds attached to the protein KRAS (background). The left circle highlights one imaging scaffold, the second displays the 3D structure of the imaging scaffold bound to KRAS, and the third shows a close-up of KRAS attached to the cancer drug AMG510. See larger image at end.

The scientists who received the 2017 Nobel Prize in chemistry were honored for their development of a technique called cryo-electron microscopy, or cryo-EM. The technology was revolutionary because it enabled scientists to see the atomic structure of biological molecules in high resolution. But cryo-EM still had a catch: It was only effective for imaging large molecules. Now, UCLA biochemists, working with pharmaceutical industry scientists, have developed a solution that will make it possible for cryo-EM to acquire high-quality images of smaller protein molecules also. The scientists engineered a 20-nanometer, cube-shaped protein structure, called a scaffold, with rigid tripod-like protrusions that hold the small proteins in place. The scaffold can be digitally removed from the picture when the imaging is being processed, leaving a composite 3D image of just the small protein scientists are analyzing.

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Decoding the Complexity of Alzheimer’s Disease: By Analyzing Epigenomic and Gene Expression Changes That Occur in Alzheimer’s Disease, Researchers Identify Cellular Pathways That Could Become New Drug Targets

Alzheimer’s disease affects more than 6 million people in the United States, and there are very few FDA-approved treatments that can slow the progression of the disease. In hopes of discovering new targets for potential Alzheimer’s treatments, MIT researchers have performed the broadest analysis yet of the genomic, epigenomic, and transcriptomic changes that occur in every cell type in the brains of Alzheimer’s patients. Using more than 2 million cells from more than 400 postmortem brain samples, the researchers analyzed how gene expression is disrupted as Alzheimer’s progresses. They also tracked changes in cells’ epigenomic modifications, which help to determine which genes are turned on or off in a particular cell. Together, these approaches offer the most detailed picture yet of the genetic and molecular underpinnings of Alzheimer’s.

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Elk Hoof Disease Likely Causes Systemic Changes

Elk treponeme-associated hoof disease, previously thought to be limited to deformations in elks’ hooves, appears to create molecular changes throughout the animal’s system, according to epigenetic research from Washington State University (WSU). The findings, published September 16, 2023 in the journal Scientific Reports, also suggest those changes may be heritable. It remains to be seen though whether this means subsequent generations of elk may be more, or less, prone to catching the devastating disease that severely impairs the elk’s ability to find food and escape predators. The open-access article is titled “Systemic Epigenome-Wide Association Study of Elk Treponeme-Associated Hoof Disease.”

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Compound d16 Reduces Tumor Growth and Overcomes Therapeutic Resistance in Mutant p53-Bearing Cancers

p53
Researchers at Baylor College of Medicine have developed a new compound called d16 that can reduce tumor growth and overcome therapeutic resistance in mutant p53-bearing cancers in the lab. The findings, published in the journal Cancer Research Communications, a journal of the American Association for Cancer Research, open opportunities for new combination therapies for these difficult-to-treat cancers. The open-access article is titled” DNA2 Nuclease Inhibition Confers Synthetic Lethality in Cancers with Mutant p53 and Synergizes With PARP Inhibitors.”

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2023 Rockefeller Award Honoring Women Scientists Goes to Lily Jan and Eve Marder

Groundbreaking neuroscientists Lily Jan and Eve Marder have jointly received the 2023 Pearl Meister Greengard Prize, an award which recognizes outstanding women scientists. The award was presented by Ellen V. Futter, president emerita of the American Museum of Natural History, in a ceremony on The Rockefeller University campus on September 20. “This year’s awardees are two outstanding scientists who have made fundamental contributions to neurobiology,” says Michael W. Young, PhD, Richard and Jeanne Fisher Professor, Nobel Laureate, and Chair of the Pearl Meister Greengard Prize selection committee. “Lily Jan’s work led to the first molecular description of the potassium channel, which allows a nerve to carry electrical impulses, and Eve Marder has revealed how populations of neurons interact to produce behavior and how behavioral flexibility can be built into neural circuits.”

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New Faculty Member at Rockefeller Works to Untangle Mysteries of RNA Folding

An essentially inert thread of genetic information, RNA reaches its potential upon folding into specific 3D structures. Only then can RNA catalyze biochemical reactions, aid in protein synthesis, and regulate the cell. Life as we know it therefore hinges not only on RNA, but on a given RNA strand adopting just the right shape to do its job. But little is known of the intricate choreography behind RNA folding. Decoding that process could unlock treatments for neurological diseases that have been linked to RNA misfolding, such as amyotrophic lateral sclerosis (ALS). It could also lead to novel drugs for short-circuiting replication of RNA viruses such as SARS-CoV-2. Untold discoveries may be unleashed once scientists unpack what makes one of life’s most fundamental molecules tick. Steve L. Bonilla, PhD, the newest addition to The Rockefeller University faculty and one of the first scientists who used cryo-electron microscopy (cryo-EM) to capture small and dynamic RNA 3D structures, is a structural biologist who studies how RNA folds and how the structure of RNA helps viruses replicate. Dr. Bonilla will join Rockefeller on October 1, 2023 as a tenure-track assistant professor, and Head of the Laboratory of RNA Structural Biology and Biophysics.

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Impact of Parental Relatedness on Type 2 Diabetes and Other Common Diseases Uncovered; Risk of Developing Several Complex Genetic Diseases May Be Increased by the Level of Consanguinity in Individuals, Scientists Find, Using a New Pioneering Approach That Removes Confounding by Sociocultural Factors

A new study finds that consanguinity–unions between close relatives–may increase the risk of common diseases such as type 2 diabetes and post-traumatic stress disorder (PTSD). Researchers from the Wellcome Sanger Institute and their collaborators at Queen Mary University of London analyzed the genomic data of diverse groups to investigate the relationship between autozygosity–a measure of genetic relatedness between an individual’s parents–and the prevalence of common diseases, with a novel method that reduces confounding due to sociocultural factors. The scientists focused their analysis on the Genes & Health cohort, which consists of British individuals of Pakistani and Bangladeshi descent, as well as individuals of both European and South Asian descent from the UK Biobank. The Genes & Health Community Advisory Board worked with the researchers to produce a publicly accessible document aimed at the lay public, explaining the study’s motivations, methodology, and findings1.

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The Buck Institute and Phenome Health Establish Partnership; Famed Scientist Lee Hood Will Co-Direct the Center for Phenomic Health at the Buck

Dr. Leroy Hood

The Buck Institute for Research on Aging and Phenome Health are joining forces in the quest to understand the biology of aging. Phenome Health, a Seattle-based nonprofit research organization led by CEO Lee Hood, MD, PhD, uses a data-driven approach to health and disease that integrates diverse types of biological big data.  The new Center for Phenomic Health at the Buck will be co-led by Dr. Hood, who joins the Buck as Chief Innovation Officer and Distinguished Professor, and by Eric Verdin, MD, Buck President and CEO. Dr. Hood is a world-renowned scientist whose technology (automated DNA sequencing) paved the way for the Human Genome Project. He is a member of the National Academy of Sciences, the National Academy of Engineering, and the National Academy of Medicine. Of the more than 6,000 scientists worldwide who belong to one or more of these academies, Dr. Hood is one of only 20 people elected to all three. Dr. Hood has co-founded 17 biotech companies and the Institute of Systems Biology. His many national and international awards include the Lasker Prize, the Kyoto Prize, and the National Medal of Science. His most recent book, coauthored with long-time collaborator Dr. Nathan Price, is titled “The Age of Scientific Wellness: Why the Future of Medicine Is Personalized, Predictive, Data-Rich, and in Your Hands.” Dr. Hood will continue to run his laboratory at Seattle’s Institute for Systems Biology which he co-founded in 2000.

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Our Internal Clock Plays Key Role in Optimizing Mental Performance

Whether you are an early bird or a night owl, your internal clock plays a critical role in maximizing your mental performance, according to a recent study from the Baycrest Centre for Geriatric Care in Toronto. This effect is so strong that it can significantly impact academic performance for adolescent students and the results of brain health assessments for older adults. “A person’s tendency to be a morning or an evening person is called their chronotype. Because of differences in chronotypes, we see significant differences in the time of day at which people are best at paying attention, learning, solving problems, making complex decisions and more,” says Dr. Lynn Hasher, Senior Scientist at Baycrest’s Rotman Research Institute, the study’s lead author and a key leader in this field of research.

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