Light-directed evolution of dynamic, multi-state, and computational protein functionalities
TL;DR
This technique could revolutionize biotechnology by making it easier to create proteins that act like biological switches, sensors, or even computers inside living cells. Such programmable proteins could lead to better medical treatments, more efficient biomanufacturing, or new types of biological devices that respond to environmental changes in real-time.
Evolving dynamic, multi-state, and computational protein functionalities is challenging because it requires selection pressure on all the states of a protein of interest (POI) and the transitions between them. To create a continuous directed evolution paradigm for such properties, we genetically engineered budding yeast for optogenetic input to switch a POI "on" and "off," which, in turn, controls a Cdk1 cyclin that is essential for one cell-cycle stage but detrimental for another. The method, "optovolution," generates dynamic selection pressure on POI cycling at the timescale of tens of minutes. We used it to evolve 19 new variants of the LOV transcription factor El222, including in vivo green-light-responsive variants allowing LOV color-multiplexing. Evolving the PhyB-Pif3 optogenetic system, we discovered that loss of YOR1 makes supplementing phycocyanobilin (PCB) unnecessary. Finally, we demonstrated the generality of the method by evolving a non-light-responsive AND gate (PEST-rtTA). Optovolution makes difficult-to-engineer protein functionalities continuously evolvable.
- 1Developed 'optovolution' - a method that uses light to create continuous evolutionary pressure on proteins that need to switch between different states
- 2Successfully evolved 19 new variants of the LOV light-sensing protein, including versions that respond to green light for better color control
- 3Discovered that removing the YOR1 gene eliminates the need for an expensive supplement (PCB) when evolving light-responsive proteins
- 4Proved the method works beyond light-responsive proteins by evolving a non-light AND gate protein
- 5Created selection pressure that operates on a timescale of tens of minutes, much faster than traditional evolution methods
Adversarial AI reveals mechanisms and treatments for disorders of consciousness
Imagine your brain is like a city with millions of roads and traffic systems. When you're awake and conscious, traffic flows in complex, coordinated patterns. In a coma, something has gone wrong — but we've never had a great way to figure out exactly which roads are broken or how to fix them. This study built a very smart AI that learned to tell the difference between 'awake brain' and 'coma brain' by studying hundreds of thousands of brainwave recordings. Then, like a detective, the AI was pitted against a simulated model of the brain to figure out: what changes in the brain's wiring would explain the difference? The AI figured out — on its own, without being told — that two key things go wrong in a coma: a specific circuit deep in the brain (called the basal ganglia indirect pathway) gets disrupted, and the brain's 'braking system' (inhibitory neurons) starts working too hard in the wrong places. The researchers then checked these predictions against real patient data, and both checked out. The AI also suggested that zapping a specific deep brain region with high-frequency electrical pulses might help wake people up — and early evidence from human patients supports this idea.
Gene conversion empowers natural selection in a clonal fish species
Unfortunately, the content of this research abstract could not be accessed due to paywall restrictions. Without being able to read the actual findings about gene conversion in clonal fish species, I cannot provide an accurate explanation of what the researchers discovered or why it matters.
The path to room-temperature superconductivity: A programmatic approach
Room-temperature superconductivity, a game-changer for technology, is still a tough puzzle, but advancements in prediction and engineering could help solve it. By improving our understanding of how to create new superconductors and control their properties, we might soon unlock this incredible phenomenon that can enhance energy efficiency and revolutionize many technologies.
Direct detection of an asteroid’s heliocentric deflection: The Didymos system after DART
NASA crashed a spacecraft into an asteroid moon called Dimorphos in 2022, and scientists have now measured that this impact actually nudged the entire asteroid system slightly off its path around the Sun. This is the first time humans have measurably changed how a celestial body orbits the Sun, proving that we can potentially deflect dangerous asteroids heading toward Earth.