Genetics – Lifeboat News: The Blog

Apr 24
2023

Study finds new pathway for clearing misfolded proteins

Misfolded proteins are toxic to cells. They disrupt normal functions and cause some age-related human degenerative diseases, like Alzheimer’s, Parkinson’s, and Huntington’s diseases. Cells work constantly to eliminate misfolded proteins, but these clearance mechanisms are still poorly understood.

In a new study published April 20 in Nature Cell Biology, researchers at Stanford University discovered a previously unknown cellular pathway for clearing misfolded proteins from the nucleus, the compartment where the cell stores, transcribes, and replicates its DNA. Keeping junk away from those processes is critical to normal cellular function. The new pathway could be a target for age-related disease therapies.

To find the new pathway, researchers in the lab of Judith Frydman, the Donald Kennedy Chair in the School of Humanities and Sciences, integrated several genetic, imaging, and biochemical approaches to understand how yeast cells dealt with misfolded proteins. For the experiments, the team restricted misfolded proteins to either the nucleus or the cytoplasm—the area inside the cell but outside the nucleus. The team visually followed the fate of the misfolded proteins through live-cell imaging and super-resolution microscopy.

Apr 23
2023

Hematopoietic Transfer of the Anti-Cancer and Lifespan-Extending Capabilities of A Genetically Engineered Blood System

A causal relationship exists among the aging process, organ decay and dis-function, and the occurrence of various diseases including cancer. A genetically engineered mouse model, termed Eklf^K74R/K74R or Eklf (K74R), carrying mutation on the well-conserved sumoylation site of the hematopoietic transcription factor KLF1/ EKLF has been generated that possesses extended lifespan and healthy characteristics including cancer resistance. We show that the high anti-cancer capability of the Eklf (K74R) mice are gender-, age-and genetic background-independent. Significantly, the anti-cancer capability and extended lifespan characteristics of Eklf (K74R) mice could be transferred to wild-type mice via transplantation of their bone marrow mononuclear cells. Targeted/global gene expression profiling analysis has identified changes of the expression of specific proteins and cellular pathways in the leukocytes of the Eklf (K74R) that are in the directions of anti-cancer and/or anti-aging. This study demonstrates the feasibility of developing a novel hematopoietic/ blood system for long-term anti-cancer and, potentially, for anti-aging.

The authors have declared no competing interest.

Apr 23
2023

Childhood abuse and biological sex linked to epigenetic changes in functional neurological disorder

Functional movement/conversion disorder (FMD), part of the spectrum of Functional Neurological Disorder (FND), is a neuropsychiatric condition marked by a range of neurological symptoms, including tremors, muscular spasms and cognitive difficulties. Despite being the second-most common cause of referrals to neurology outpatient clinics after headache, scientists have struggled to pin down the disorder’s root cause. Female sex and a history of childhood trauma are factors associated with higher risk of developing FMD, but it’s been unclear why.

A new study from investigators of the Brigham and Women’s Hospital, in collaboration with researchers at the National Institute of Neurological Disorders and Stroke, demonstrated that FMD is characterized by epigenetic changes, and that women and childhood abuse survivors with FMD have different epigenetic profiles linked to this condition. Their study, which examined the genomes of over 100 individuals and was recently published in Progress in Neuro-Psychopharmacology and Biological Psychiatry, is the first to demonstrate the occurrence of epigenetic changes in FMD.

“This study finally takes FMD out of a cloud of confusion and provides a neuroscientifically grounded explanation for why childhood trauma and female sex are associated with this disorder,” said lead author Primavera A. Spagnolo, MD, Ph.D., scientific director of the Mary Horrigan Connors Center for Women’s Health and Gender Biology and assistant professor of psychiatry at HMS.

Apr 23
2023

Epigenetic Test #5: Impact of NMN?

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Apr 21
2023

Scientists discover how X chromosome gets its shape, solving one of life’s greatest mysteries

Scientists in Britain have finally solved one of the greatest mysteries of life: how chromosomes get their X shape. Chromosomes, discovered in the late 1800s, are DNA molecules which contain the genetic material of an organism.

All chromosomes, without exception, either go through or end up with an X shape before the cells of an organism divide.

But it was always a mystery how they are X-shaped. While Biology students across the world study that chromosomes get their shape during cell division, the exact reason behind their X shape was not known.

Apr 20
2023

Dr. Oded Rechavi: Genes & the Inheritance of Memories Across Generations | Huberman Lab Podcast

In this episode, my guest is Oded Rechavi, Ph.D., professor of neurobiology at Tel Aviv University and expert in how genes are inherited, how experiences shape genes and remarkably, how some memories of experiences can be passed via genes to offspring. We discuss his research challenging long-held tenets of genetic inheritance and the relevance of those findings to understanding key biological and psychological processes including metabolism, stress and trauma. He describes the history of the scientific exploration of the “heritability of acquired traits” and how epigenetics and RNA biology can account for some of the passage of certain experience-based memories. He discusses the importance of model organisms in scientific research and describes his work on how stressors and memories can be passed through small RNA molecules to multiple generations of offspring in ways that meaningfully affect their behavior. Nature vs. nurture is a commonly debated theme; Dr. Rechavi’s work represents a fundamental shift in our understanding of that debate, as well as genetic inheritance, brain function and evolution.

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Apr 18
2023

Every base everywhere all at once: pangenomics comes of age

Multi-genome assemblies called pangenomes can capture genetic diversity in a species, but researchers are still working out how best to build and explore them.

Apr 17
2023

How do Viruses Reproduce?

https://youtube.com/watch?v=QHHrph7zDLw&feature=share

How do viruses make more copies of themselves? They do this by taking over human cells. When a virus infects a cell, it hijacks the protein-making machinery of the cell by releasing its own genetic code, or instructions, into the cell. Now, instead of making proteins for the body, the cell starts working for the virus, helping it replicate. The cell makes more and more virus particles that are released to go on and infect more cells.

Play a Kahoot! trivia game based on this animation: http://www.vaccinemakers.org/trivia.

Watch the related animation, “A Virus Attacks a Cell,” to learn how viruses get into our cells to begin the process of reproduction: https://youtu.be/jkNxmTrrZSk.

Animation created by and for the Vaccine Makers Project.
The Vaccine Makers Project gratefully acknowledges the ongoing collaboration and partnership with XVIVO, creator of medical animations and scientific media: https://xvivo.com.
Copyright © 2016, Medical History Pictures, Inc. All rights reserved.

The Vaccine Makers Project (VMP) is the classroom-based program of the Vaccine Education Center at the Children’s Hospital of Philadelphia (VEC at CHOP). The Center’s team is composed of scientists, physicians, mothers and fathers devoted to the study and prevention of infectious diseases. The Center was launched in October 2000 to provide accurate, comprehensive and up-to-date information about vaccines and the diseases they prevent. The VMP program is committed to public education about vaccine science via scientifically supported, historically accurate, and emotionally compelling content.

Access the VMP’s free classroom materials: http://www.VaccineMakers.org.

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Apr 16
2023

Feng Zhang’s Delivery Platform Launched by Aera Therapeutics

Finally got around to reading through the Feng Zhang laboratory’s amazing SEND (Selective Endogenous ENcapsidation for cellular Delivery) paper!

[Link: https://www.science.org/doi/10.1126/science.abg6155] The authors describe a new gene therapy delivery vehicle which leverages virus-like particles (VLPs) originally produced within human cells. These VLPs arise from ancient retroviral genomic fragments that were integrated into the human genome long ago and eventually were utilized to benefit our own physiology. Because they are recognized as ‘self’ by the immune system, the VLPs have potential as a novel gene therapy delivery modality. In this paper, Segel et al.

Aera’s strategy is to harness these proteins, and structures, to move the cargo of genetic medicines: RNAi, antisense RNA, mRNA, or a genetic editing payload, for example. To date, proteins and nucleic acids have been packaged. The company’s first goal is to move smaller nucleic acids like ASOs and siRNA from cell to cell.

What is known about PNPs is “quite limited,” said Akinc. Their role in the human body is particularly opaque. The literature goes back only to 2018. They are called virus-like particles (VLPs) in the literature, but Aera thinks that PNP is a more technically accurate name.

Aera Therapeutics is announcing its launch today, they said, with “a vision to harness its proprietary delivery platform to unlock the potential of genetic medicines.” Akinc doesn’t specify any disease targets but emphasizes the unmet need for diseases that affect the central nervous system.