资源环境科技发展态势分析平台

All viruses require strategies to inhibit or evade the immune pathways of cells that they infect. The viruses that infect bacteria, bacteriophages (phages), must avoid immune pathways that target nucleic acids, such as CRISPR-Cas and restriction-modification systems, to replicate efficiently(1). Here we show that jumbo phage phi KZ segregates its DNA from immunity nucleases of its host, Pseudomonas aeruginosa, by constructing a proteinaceous nucleus-like compartment. phi KZ is resistant to many immunity mechanisms that target DNA in vivo, including two subtypes of CRISPR-Cas3, Cas9, Cas12a and the restriction enzymes HsdRMS and EcoRI. Cas proteins and restriction enzymes are unable to access the phage DNA throughout the infection, but engineering the relocalization of EcoRI inside the compartment enables targeting of the phage and protection of host cells. Moreover, phi KZ is sensitive to Cas13a-a CRISPR-Cas enzyme that targets RNA-probably owing to phage mRNA localizing to the cytoplasm. Collectively, we propose that Pseudomonas jumbo phages evade a broad spectrum of DNA-targeting nucleases through the assembly of a protein barrier around their genome.

Quantum mechanics governs the microscopic world, where low mass and momentum reveal a natural wave-particle duality. Magnifying quantum behaviour to macroscopic scales is a major strength of the technique of cooling and trapping atomic gases, in which low momentum is engineered through extremely low temperatures. Advances in this field have achieved such precise control over atomic systems that gravity, often negligible when considering individual atoms, has emerged as a substantial obstacle. In particular, although weaker trapping fields would allow access to lower temperatures(1,2), gravity empties atom traps that are too weak. Additionally, inertial sensors based on cold atoms could reach better sensitivities if the free-fall time of the atoms after release from the trap could be made longer(3). Planetary orbit, specifically the condition of perpetual free-fall, offers to lift cold-atom studies beyond such terrestrial limitations. Here we report production of rubidium Bose-Einstein condensates (BECs) in an Earth-orbiting research laboratory, the Cold Atom Lab. We observe subnanokelvin BECs in weak trapping potentials with free-expansion times extending beyond one second, providing an initial demonstration of the advantages offered by a microgravity environment for cold-atom experiments and verifying the successful operation of this facility. With routine BEC production, continuing operations will support long-term investigations of trap topologies unique to microgravity(4,5), atom-laser sources(6), few-body physics(7,8)and pathfinding techniques for atom-wave interferometry(9-12).

VirtualFlow, an open-source drug discovery platform, enables the efficient preparation and virtual screening of ultra-large ligand libraries to identify molecules that bind with high affinity to target proteins.

On average, an approved drug currently costs US$2-3 billion and takes more than 10 years to develop(1). In part, this is due to expensive and time-consuming wet-laboratory experiments, poor initial hit compounds and the high attrition rates in the (pre-)clinical phases. Structure-based virtual screening has the potential to mitigate these problems. With structure-based virtual screening, the quality of the hits improves with the number of compounds screened(2). However, despite the fact that large databases of compounds exist, the ability to carry out large-scale structure-based virtual screening on computer clusters in an accessible, efficient and flexible manner has remained difficult. Here we describe VirtualFlow, a highly automated and versatile open-source platform with perfect scaling behaviour that is able to prepare and efficiently screen ultra-large libraries of compounds. VirtualFlow is able to use a variety of the most powerful docking programs. Using VirtualFlow, we prepared one of the largest and freely available ready-to-dock ligand libraries, with more than 1.4 billion commercially available molecules. To demonstrate the power of VirtualFlow, we screened more than 1 billion compounds and identified a set of structurally diverse molecules that bind to KEAP1 with submicromolar affinity. One of the lead inhibitors (iKeap1) engages KEAP1 with nanomolar affinity (dissociation constant (K-d) = 114 nM) and disrupts the interaction between KEAP1 and the transcription factor NRF2. This illustrates the potential of VirtualFlow to access vast regions of the chemical space and identify molecules that bind with high affinity to target proteins.