Lifeboat Foundation

Identifying therapeutic targets for neurodegenerative conditions is often challenging due to the limited accessibility of reproducible, scalable in vitro cell models. Genome-level CRISPR screens are useful for these studies but performing screens that include the necessary replicates requires billions of cells. Human iPSC-derived cells can provide the needed scale, however, the complex process of directed differentiation is time-consuming, resource-intensive, and rarely feasible. Furthermore, delivering ribonucleases by transfection or transduction is inefficient in human iPSC-derived cells, especially delicate cell types like neurons. As a result, scientists often rely on immortalized cell lines, which do not accurately represent human biology or disease states, to run large-scale CRISPR screens.

In this GEN webinar, two experts will discuss solutions for running large-scale CRISPR screens to identify therapeutic targets for neurodegenerative diseases. They will present ioCRISPR-Ready Cells™: human iPSC-derived cells precision reprogrammed with opti-ox™, that constitutively express Cas9 nuclease, which are built for rapidly generating gene knockouts and CRISPR screens. During the webinar, you’ll learn about two peer-reviewed studies that performed large scale CRISPR knockout screens using opti-ox powered glutamatergic neurons with stable Cas9 expression. The first study demonstrates a loss-of-function genetic screen using a human druggable genome library. The second study investigated possible regulators of the RNA binding motif 3 protein, whose enhanced expression is highly neuroprotective both in vitro and in vivo.

A cancer drug in the final stages of clinical trials may be able to help treat a range of inflammatory diseases including gout, heart failure, cardiomyopathy, and atrial fibrillation, according to scientists at the University of Cambridge.

Their findings are published in the Journal of Clinical Investigation in an article titled, “PLK1 inhibition dampens NLRP3 inflammasome-elicited response in inflammatory disease models.”

“Unabated activation of the NLR family pyrin domain–containing 3 (NLRP3) inflammasome is linked with the pathogenesis of various inflammatory disorders. Polo-like kinase 1 (PLK1) has been widely studied for its role in mitosis,” wrote the researchers. “Here, using both pharmacological and genetic approaches, we demonstrate that PLK1 promoted NLRP3 inflammasome activation at cell interphase. Using an unbiased proximity-dependent biotin identification (Bio-ID) screen for the PLK1 interactome in macrophages, we show an enhanced proximal association of NLRP3 with PLK1 upon NLRP3 inflammasome activation. We further confirmed the interaction between PLK1 and NLRP3 and identified the interacting domains.”

In this study we aimed to detect epigenetic and genetic loci associated with PTSD in a homogeneous cohort of traumatized police officers. Both a genome-wide and hypothesis-driven replication approach did not result in DMPs between PTSD patients and trauma-exposed controls. GSE analysis on the top 100 DMPs showed, however, a plausible association of the dopaminergic neurogenesis pathway with PTSD. Furthermore, we observed one DMR located at the PAX8 gene suggesting consistent hypermethylation in PTSD patients. Genetic analyses yielded three CpG-SNPs significantly associated with PTSD. Of these, one CpG-SNP, located at the CACNA1C locus, was also significantly associated with PTSD in an independent replication sample of trauma-exposed children. Notably, this result shows that the Illumina 450K array is not restricted to epigenetic surveys but can provide informative genetic data as well.

Although our sample was small, it was highly homogenous as all participants were former or current police officers, and cases and controls were matched for sex, age, education, and years of police service. All participants reported multiple prior traumatic events, without significant group differences in reported types of traumatic experiences. PTSD patients fulfilled current diagnostic criteria for PTSD, while our trauma-exposed controls had minimal PTSD symptoms and did not report lifetime PTSD or other trauma-related psychiatric disorders. Thus our controls were apparently resilient to adverse mental health outcome of trauma. This study design, including extreme phenotypes following similar trauma load, was considered to favor detection of PTSD-associated loci, as also suggested by others [22]. Nevertheless, our genome-wide survey clearly remains limited in statistical power.

Emmett Short discusses these comments on this episode of Lifespan News.

But first, the mad scientist David Sinclair, this time with Peter Diamandis at Abundance 360, giving more details into human trials for the genetic engineering side of the technology versus the chemical and pill side of the technology. Which would you want more? We’ll also hear David’s thoughts on how AI will affect the advancement of this tech. Spoiler: A lot. I’m going to play the best parts and add my commentary along the way.

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According to the Chinese Ministry of State Security, “certain countries” are likely working on incredibly potent ethnic bioweapons.

China has blown the whistle on the potential dangers of what it calls “genetic weapons” that could prove to be an incredibly potent weapon of mass destruction, the Global Times reports. On Monday, October 20, 2023, the Chinese Ministry of State Security released a statement on WeChat warning that a “certain” foreign non-governmental organization (NGO) had recruited Chinese “volunteers” to collect biodiversity distribution data under the guise of biological species research to steal China’s species data.

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This Review discusses how embryonic transcriptional programs, such as epithelial–mesenchymal plasticity and stemness, may be harnessed in adult tissues to drive processes and diseases such as regeneration and cancer.

Caps on the ends of chromosomes are critical for maintaining genetic integrity and promoting healthy aging.

A new study is finding that greener neighborhoods protect telomeres which prevent aging on a genetic level.

The role of telomeres in aging

Telomeres are repetitive sequences of DNA found at the ends of chromosomes that play a crucial role in preserving the integrity and stability of the genetic material within a cell.

Continue reading “Greener neighborhoods stop us from aging on a genetic level” »