Progeria Treatment Breakthroughs and Genome Shrinking Efforts
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The Quest to Shrink Genomes
The synthetic yeast initiative is a global collaboration aimed at creating the first synthetic eukaryotic genome. Researchers are chemically synthesizing each chromosome of Saccharomyces cerevisiae in laboratories worldwide. In this process, they are also integrating additional features, such as short DNA sequences around each gene, which allow for the genes to be cut out and rearranged randomly, a technique known as "scrambling."
A recent study published in Genome Biology by scientists from the Shenzhen Institute of Synthetic Biology and the Manchester Institute of Biotechnology focused on scrambling the left arm of chromosome 12, referred to as synXIIL. This rearrangement led to the discovery that 39 out of 65 nonessential genes could be entirely removed following the scrambling process. The project is ongoing, and the international team plans to assemble all synthesized chromosomes, potentially allowing for large-scale genome reduction.
Base Editing Rescues Progeria Syndrome in Mice
Progeria, a genetic disorder characterized by accelerated aging, affects children who typically only live about 14 years due to a mutation in the LMNA gene (specifically a C•G-to-T•A change). A new study in Nature describes how researchers employed an adenine base editor—capable of converting A•T base pairs to G•C pairs—to correct this mutation in live mice and fibroblast cells from affected children.
The application of the base editor to fibroblast cells resulted in an impressive 87–91% mutation correction. In mice, a single injection of a virus containing the adenine base editor nearly doubled their median lifespan, extending it from 215 days to 510 days.
A New Enzyme Enhances Photosynthesis
Photosynthesis, Earth's essential metabolic process, is often inefficient, with RuBisCO, a key protein, fixing only three carbon dioxide molecules per second. In contrast, carbonic anhydrase operates at a much higher efficiency, processing one million molecules per second.
A recent study introduced a novel pathway called TaCo (tartronyl-CoA), which integrates glycolate directly into central carbon metabolism. This pathway, unlike natural photosynthesis, assimilates carbon dioxide without releasing it. The research team created a unique enzyme, not found in nature, to establish this pathway. Tobias Erb, a lead author from the Max Planck Institute for Terrestrial Microbiology, noted that the TaCo pathway could serve as an alternative to photorespiration and connect with other synthetic carbon fixation processes, such as the CETCH cycle.
Rapid-Fire Highlights
- Researchers enhanced wheat crops by inserting five genes, providing them protection against Puccinia graminis, the fungus responsible for stem rust, leading to significant yield preservation.
- A naturally occurring single-guide RNA for S. pyogenes Cas9 was discovered, simplifying genetic editing techniques.
- David Baker's lab developed 2D protein materials designed with "dihedral protein building blocks".
- A new engineered leucyl tRNA synthetase-tRNA pair allowed researchers to incorporate citrulline into proteins at specific locations.
- A study proposed a statistical approach to genetic engineering, improving the efficiency of modifications.
- Researchers engineered a protein sequence that successfully targeted and killed Mycobacterium tuberculosis, sparing surrounding lung tissue.
Have a great week ahead!
Until Friday,
— Niko
Bonus Tweet: David Liu discusses base editors and their role in correcting the mutation responsible for progeria, a highlight from this newsletter.