Scientists achieve 3D molecular mapping with breakthrough hybrid microscope
The microscope combines polarized fluorescence, which measures molecular orientation, with a dual-view light sheet microscope (diSPIM) that captures depth details in a sample. This technology can be useful for studying proteins, as they change their 3D orientation in response to their environment to interact with other molecules and perform their functions.
According to Talon Chandler of CZ Biohub San Francisco, the study's first author and a former University of Chicago graduate student who conducted part of this research at MBL, the instrument allows researchers to record changes in 3D protein orientation.
This capability provides insights that may be missed when looking only at a molecule's position. One example is imaging molecules in the spindle of a dividing cell, a challenge that has long been studied at MBL and other research institutions.
The study's co-author, Rudolf Oldenbourg, a senior scientist at MBL, explained that traditional microscopy, including polarized light, can effectively image the spindle when it is perpendicular to the viewing direction. However, when the spindle is tilted, the readout becomes ambiguous. The new instrument overcomes this limitation by adjusting for tilt, allowing researchers to accurately capture both the 3D orientation and position of spindle molecules, such as microtubules.
Now, the team aims to improve the system's speed to capture how the position and orientation of structures change in live samples over time. They also hope that future fluorescent probes will expand its use, allowing researchers to image a wider range of biological structures.
The idea for the microscope originated in 2016 through brainstorming sessions among microscopy innovators at MBL. Hari Shroff of HHMI Janelia, then at the National Institutes of Health (NIH) and an MBL Whitman Fellow, was using his custom-built diSPIM microscope at MBL, developed in collaboration with Abhishek Kumar, now at MBL.
The diSPIM microscope features two imaging paths that intersect at a right angle, allowing researchers to illuminate and capture the sample from both perspectives. This dual-view approach improves depth resolution compared to a single view and provides greater control over polarization during imaging.
Shroff and Oldenbourg recognized that the dual-view microscope could help overcome a limitation of polarized light microscopy - its difficulty in efficiently illuminating a sample with polarized light along the direction of light propagation. By incorporating two orthogonal views, they saw an opportunity to improve the detection of polarized fluorescence and explored using the diSPIM system for such measurements.
https://www.youtube.com/shorts/AZ3OEw3epzU
Shroff collaborated with Patrick La Riviere from the University of Chicago, whose student Talon Chandler joined the project at MBL. Chandler's doctoral thesis focused on integrating the two systems, working in Oldenbourg's lab for a year. The team, including Shalin Mehta, outfitted the diSPIM with liquid crystals to control input polarization direction.
Chandler dedicated a significant amount of time to exploring how to reconstruct the data and maximize what could be recovered from it. Co-author Min Guo, then at Shroff's previous lab at NIH, also worked extensively on this aspect, and together, they achieved their goal of full 3D reconstructions of molecular orientation and position.
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Chicago Tribune
5 days ago
- Chicago Tribune
To know them is to loath them: Oak Park's Alec Nevala-Lee finds a niche, writing about science's biggest jerks
Luis W. Alvarez, physicist, genius, conspiracy debunker, military hawk, Zelig, University of Chicago dyspeptic, to cut to the chase, was not a very pleasant man. He was not especially liked by colleagues. It's hard to tell if he was even liked by his kids. And so, for Alec Nevala-Lee of Oak Park, who has become an underrated biographer of Great Jerks in Science, Alvarez was perfect. Nevala-Lee's previous biography was on Buckminster Fuller, architect, futurist, longtime professor at Southern Illinois University, but also an infamously obtuse, inscrutable mansplainer's mansplainer — his lectures seemed to go on for days. Before that, Nevala-Lee wrote 'Astounding,' a harrowing account of the men behind mid-century science fiction, particularly editor John W. Campbell, who could be described charitably as fascist. His next book, already in the works, is about those lovable scamps behind the RAND Corporation, the most despised think tank in history. Am I nuts or do I see a pattern here? 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Deep down, our figures like this, they all have the same problems.' By the way, since you're probably wondering, for the record, Nevala-Lee is a nice guy. cborrelli@
WIRED
06-08-2025
- WIRED
Nuclear Experts Say Mixing AI and Nuclear Weapons Is Inevitable
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Last year, Air Force General Anthony J. Cotton, the military leader in charge of America's nukes, gave a long speech at a conference about the importance of adopting AI. He said the nuclear forces were 'developing artificial intelligence or AI-enabled, human led, decision support tools to ensure our leaders are able to respond to complex, time-sensitive scenarios.' What keeps Wolfsthal up at night is not the idea that a rogue AI will start a nuclear war. 'What I worry about is that somebody will say we need to automate this system and parts of it, and that will create vulnerabilities that an adversary can exploit, or that it will produce data or recommendations that people aren't equipped to understand, and that will lead to bad decisions,' he says. Launching a nuclear weapon is not as simple as one leader in China, Russia, or the US pushing a button. 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Yahoo
29-07-2025
- Yahoo
What Happens To Your Consciousness After You Die?
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