Lifeboat Foundation

Over the recent decades, comprehensive genome-wide association studies (GWAS) have indicated the potential influence of genetic factors on one’s alcohol consumption volume and identified over 100 related variants^6,7. However, a predominant proportion of the identified variants are localized within noncoding regions, and their effect sizes tend to be small, making interpretation and identification of the causal gene challenging⁸. In addition, previous GWAS mainly utilized imputed genotype data, which only cover limited regions of the genome, and thus may have missed many potential genes. Furthermore, GWAS studies focused mainly on common variants, and few studies have investigated rare variants associated with alcohol consumption, which yield greater potential to interpret biological function and elucidate mechanisms⁹. Although there are studies that have attempted to leverage exome chip data to identify rare variants contributing to alcohol consumption, the sample size was small and limited regions of the whole exome were examined¹⁰.

The introduction of whole exome sequencing (WES) provides a great chance to overcome the limitations of previous genetic studies on alcohol consumption with a substantially larger amount of rare and ultra-rare protein-coding variants^11,12,13. Collapsing of loss-of-function (LOF) variants helps estimate the effect direction of associated genes^13,14. When combined with large-scale population cohorts with multi-modal phenotypic data, WES would greatly facilitate our understanding of the genetic underpinnings of alcohol consumption as well as its implication on physical and mental health⁶. However, to our knowledge, there have been few large-scale WES studies on alcohol consumption, let alone elucidating the potential implications of the identified genes^10,15. Meanwhile, as indicated by a previous genome-wide association study, significant genetic associations existed between alcohol consumption and several body health phenotypes⁷. The application of phenome-wide analysis for alcohol-related genes can help extend and deepen our current comprehension of the association between alcohol consumption and human health.

Hence, aiming to refine the genetic architecture of alcohol consumption, we conduct an exome-wide association study (ExWAS) for alcohol consumption among 304,119 individuals from the UK Biobank (UKB). We also examine the rare-variant associations with genes reported by previous GWAS^6,7,16,17. Finally, we provide biological insights into the identified genes via bioinformatics analyses and phenome-wide association analysis (PheWAS).

Genome editing stands as one of the most transformative scientific breakthroughs of our time. It allows us to dive into the very code of life and make precise modifications. Imagine being able to rewrite the genetic instructions that determine almost everything about an organism—how it looks, behaves, interacts with its environment, and its unique characteristics. This is the power of genome editing.

We use genome editing tools to tweak the genetic sequences of microbes, animals, and plants. Our goal? To develop desired traits and eliminate unwanted ones. This technology’s impact has been felt across biotechnology, human therapeutics, and agriculture, bringing rapid advancements and solutions.

The most widely used proteins in genome editing are Cas9 and Cas12a. These proteins are like the scissors of the genetic world, allowing us to cut and edit DNA. However, they are quite bulky, consisting of 1,000–1,350 amino acids. Advanced editing technologies like base editing and prime editing require the fusion of additional proteins with Cas9 and Cas12a, making them even bulkier. This bulkiness poses a challenge to delivering these proteins efficiently into cells, where the genetic material resides.

Scientists have connected two organoids together with an axon bundle, to study how brain areas communicate. They sent signals back and forth and responded to external stimulation. This could be a step toward biocomputing.

Learn about: axons, white matter, re-entry, optogenetics, myelination, entrainment, short-term potentiation.

Continue reading “Brain Organoids Communicate: A Step Toward ‘Organoid Intelligence’” »

In multicellular organisms, many biological pathways exhibit a curious structure, involving sets of protein variants that bind or interact with one another in a many-to-many fashion. What functions do these seemingly complicated architectures provide? And can similar architectures be useful in synthetic biology? Here, Dr. Elowitz discusses recent work in his lab that shows how many-to-many circuits can function as versatile computational devices, explore the roles these computations play in natural biological contexts, and show how many-to-many architectures can be used to design synthetic multicellular behaviors.

About Michael Elowitz.
Michael Elowitz is a Howard Hughes Medical Institute Investigator and Roscoe Gilkey Dickinson Professor of Biology and Biological Engineering at Caltech. Dr. Elowitz’s laboratory has introduced synthetic biology approaches to build and understand genetic circuits in living cells and tissues. As a graduate student with Stanislas Leibler, Elowitz developed the Repressilator, an artificial genetic clock that generates gene expression oscillations in individual E. coli cells. Since then, his lab has continued to design and build synthetic genetic circuits, bringing a “build to understand” approach to bacteria, yeast, and mammalian cells. He and his group have shown that gene expression is intrinsically stochastic, or ‘noisy’, and revealed how noise functions to enable probabilistic differentiation, time-based regulation, and other functions. Currently, Elowitz’s lab is bringing synthetic approaches to understand and program multicellular functions including multistability, cell-cell communication, epigenetic memory, and cell fate control, and to provide foundations for using biological circuits as therapeutic devices. His lab also co-develops systems such as “MEMOIR” that allows cells to record their own lineage histories and tools for RNA export, and precise gene expression. Elowitz received his PhD in Physics from Princeton University and did postdoctoral research at Rockefeller University. Honors include the HFSP Nakasone Award, MacArthur Fellowship, Presidential Early Career Award, Allen Distinguished Investigator Award, the American Academy of Arts and Sciences, and election to the National Academy of Sciences.

Continue reading “Many-to-Many Networks: Multifunctional Modules for Multicellularity — Michael Elowitz” »

Summary: Researchers have discovered how glial cells can be reprogrammed into neurons through epigenetic modifications, offering hope for treating neurological disorders. This reprogramming involves complex molecular mechanisms, including the transcription factor Neurogenin2 and the newly identified protein YingYang1, which opens chromatin for reprogramming.

The study reveals how coordinated epigenome changes drive this process, potentially leading to new therapies for brain injury and neurodegenerative diseases.

Researchers have significantly improved gene-editing techniques. This new method, called eePASSIGE, can insert or replace entire genes in human cells with much higher efficiency than previous methods. This advancement could lead to a single gene therapy for diseases caused by various mutations in a single gene, like cystic fibrosis. Traditionally, gene therapy required a different treatment for each mutation.

EePASSIGE combines prime editing, which edits small stretches of DNA, with new enzymes that insert large pieces of DNA. This allows scientists to introduce a healthy copy of a gene directly where it belongs in the genome.

“This is one of the first examples of targeted gene integration with potential for therapeutic applications,” said Dr. David Liu, senior author of the study. “If these efficiencies translate to patients, many genetic diseases could be treated.”

Learn more about the Cognitive Science Student Association and the California Cognitive Science Conference at https://cssa.berkeley.edu.

Amy Arnsten — Yale University.

Continue reading “The Effects of Stress on Prefrontal Cortical Function” »

Restraining or slowing ageing hallmarks at the cellular level have been proposed as a route to increased organismal lifespan and healthspan. Consequently, there is great interest in anti-ageing drug discovery. However, this currently requires laborious and lengthy longevity analysis. Here, we present a novel screening readout for the expedited discovery of compounds that restrain ageing of cell populations in vitro and enable extension of in vivo lifespan.

Using Illumina methylation arrays, we monitored DNA methylation changes accompanying long-term passaging of adult primary human cells in culture. This enabled us to develop, test, and validate the CellPopAge Clock, an epigenetic clock with underlying algorithm, unique among existing epigenetic clocks for its design to detect anti-ageing compounds in vitro. Additionally, we measured markers of senescence and performed longevity experiments in vivo in Drosophila, to further validate our approach to discover novel anti-ageing compounds. Finally, we bench mark our epigenetic clock with other available epigenetic clocks to consolidate its usefulness and specialisation for primary cells in culture.

We developed a novel epigenetic clock, the CellPopAge Clock, to accurately monitor the age of a population of adult human primary cells. We find that the CellPopAge Clock can detect decelerated passage-based ageing of human primary cells treated with rapamycin or trametinib, well-established longevity drugs. We then utilise the CellPopAge Clock as a screening tool for the identification of compounds which decelerate ageing of cell populations, uncovering novel anti-ageing drugs, torin2 and dactolisib (BEZ-235). We demonstrate that delayed epigenetic ageing in human primary cells treated with anti-ageing compounds is accompanied by a reduction in senescence and ageing biomarkers. Finally, we extend our screening platform in vivo by taking advantage of a specially formulated holidic medium for increased drug bioavailability in Drosophila. We show that the novel anti-ageing drugs, torin2 and dactolisib (BEZ-235), increase longevity in vivo.

Researchers have developed a genetic algorithm for designing phononic crystal nanostructures, significantly advancing quantum computing and communications.

The new method, validated through experiments, allows precise control of acoustic wave propagation, promising improvements in devices like smartphones and quantum computers.

Quantum Computing Revolution