Lifeboat Foundation

Researchers have discovered a “spatial grammar” in DNA that redefines the role of transcription factors in gene regulation, influencing our understanding of genetic variations and disease.

A recently uncovered code within DNA, referred to as “spatial grammar,” may unlock the secret to how gene activity is encoded in the human genome.

This breakthrough finding, identified by researchers at Washington State University and the University of California, San Diego and published in Nature, revealed a long-postulated hidden spatial grammar embedded in DNA. The research could reshape scientists’ understanding of gene regulation and how genetic variations may influence gene expression in development or disease.

To be able to make full use of these modeling systems, researchers have developed a growing toolkit of genetic modification techniques. These techniques can be applied to mature brain organoids or to the preceding embryoid bodies (EBs) and founding cells. This review will describe techniques used for transient and stable genetic modification of brain organoids and discuss their current use and respective advantages and disadvantages. Transient approaches include adeno-associated virus (AAV) and electroporation-based techniques, whereas stable genetic modification approaches make use of lentivirus (including viral stamping), transposon and CRISPR/Cas9 systems. Finally, an outlook as to likely future developments and applications regarding genetic modifications of brain organoids will be presented.

The development of brain organoids (Kadoshima et al., 2013; Lancaster et al., 2013) has opened up new ways to study brain development and evolution as well as neurodevelopmental disorders. Brain organoids are multicellular 3D structures that mimic certain aspects of the cytoarchitecture and cell-type composition of certain brain regions over a particular developmental time window (Heide et al., 2018). These structures are generated by differentiation of induced pluripotent stem cells (iPSCs) or embryonic stem cells (ESCs) into embryoid bodies followed by, or combined, with neural induction (Kadoshima et al., 2013; Lancaster et al., 2013). In principle, two different classes of brain organoid protocols can be distinguished, namely: (i) the self-patterning protocols which produce whole-brain organoids; and (ii) the pre-patterning protocols which produce brain region-specific organoids (Heide et al., 2018).

Proposed lunar biorepository could store genetic samples without electricity or liquid nitrogen. New research led by scientists at the Smithsonian proposes a plan to safeguard Earth’s imperiled biodiversity by cryogenically preserving biological material on the moon. The moon’s permanently shadowed craters are cold enough for cryogenic preservation without the need for electricity or liquid nitrogen, according to the researchers.

The paper, published today in BioScience and written in collaboration with researchers from the Smithsonian’s National Zoo and Conservation Biology Institute (NZCBI), Smithsonian’s National Museum of Natural History, Smithsonian’s National Air and Space Museum and others, outlines a roadmap to create a lunar biorepository, including ideas for governance, the types of biological material to be stored and a plan for experiments to understand and address challenges such as radiation and microgravity. The study also demonstrates the successful cryopreservation of skin samples from a fish, which are now stored at the National Museum of Natural History.

“Initially, a lunar biorepository would target the most at-risk species on Earth today, but our ultimate goal would be to cryopreserve most species on Earth,” said Mary Hagedorn, a research cryobiologist at NZCBI and lead author of the paper. “We hope that by sharing our vision, our group can find additional partners to expand the conversation, discuss threats and opportunities and conduct the necessary research and testing to make this biorepository a reality.”

An iterative engineering approach to improve prime editor delivery helped scientists correct genetic vision defects in mice.

A new study, funded by the National Institute of Mental Health and the National Institute of Neurological Disorders and Stroke, describes a promising way to carry genetic material into the brain to reach cellular targets.

A new open-access RNA sequencing dataset, MAGE, of 731 individuals across geographically diverse human populations provides a valuable resource to study genetic diversity and evolution and expands the capacity to identify new genetic associations.

It’s no revelation that the human body undergoes natural wear and tear as we age. But you might be surprised to discover that this process isn’t as gradual as we’d presumed.

A recent study reveals some remarkable truths about aging, specifically when and how our bodies start to ‘break down’

The man at the helm of the study is Michael Snyder. Chair of genetics at Stanford School of Medicine and recognized for his exceptional contribution to the field, his team’s research provides some fascinating insights into the specifics of our biological aging process.

Bacteria defend themselves from viral infection using diverse immune systems, many of which sense and target foreign nucleic acids. Defense-associated reverse transcriptase (DRT) systems provide an intriguing counterpoint to this immune strategy by instead leveraging DNA synthesis, but the identities and functions of their DNA products remain largely unknown. Here we show that DRT2 systems execute an unprecedented immunity mechanism that involves de novo gene synthesis via rolling-circle reverse transcription of a non-coding RNA (ncRNA). Unbiased profiling of RT-associated RNA and DNA ligands in DRT2-expressing cells revealed that reverse transcription generates concatenated cDNA repeats through programmed template jumping on the ncRNA. The presence of phage then triggers second-strand cDNA synthesis, leading to the production of long double-stranded DNA. Remarkably, this DNA product is efficiently transcribed, generating messenger RNAs that encode a stop codon-less, never-ending ORF (neo) whose translation causes potent growth arrest. Phylogenetic analyses and screening of diverse DRT2 homologs further revealed broad conservation of rolling-circle reverse transcription and Neo protein function. Our work highlights an elegant expansion of genome coding potential through RNA-templated gene creation, and challenges conventional paradigms of genetic information encoded along the one-dimensional axis of genomic DNA.

One-Sentence Summary Bacterial reverse transcriptases synthesize extrachromosomal genes via rolling-circle amplification to confer potent antiviral immunity.

Columbia University has filed a patent application related to this work. S.H.S. is a co-founder and scientific advisor to Dahlia Biosciences, a scientific advisor to CrisprBits and Prime Medicine, and an equity holder in Dahlia Biosciences and CrisprBits.

In the quest to unravel the complexities of neural circuits, scientists are beginning to use genetically encoded voltage indicators (GEVIs) to visualize electrical activity in the brain. These indicators are crucial for understanding how neurons communicate and process information. However, the effectiveness of one-photon (1P) versus two-photon (2P) voltage imaging has remained a topic of debate. A recent study by researchers at Harvard University sheds light on the relative merits and limitations of these two imaging techniques, providing valuable insights for the scientific community.