#nature methods

Created line of spinal cord neural stem cells shows diverse promise

Researchers at University of California San Diego School of Medicine report that they have successfully created spinal cord neural stem cells (NSCs) from human pluripotent stem cells (hPSCs) that differentiate into a diverse population of cells capable of dispersing throughout the spinal cord and can be maintained for long periods of time.

The achievement, described in the August 6 online issue of

How a Yeast Cell Helps Crack Open the ‘Black Box’ Behind Artificial Intelligence

“It seems like every time you turn around, someone is talking about the importance of artificial intelligence and machine learning,” said Trey Ideker, a researcher at the School of Medicine and the Department of Bioengineering at the University of California San Diego. “But all of these systems are so-called ‘black boxes.’ They can be very predictive, but we don’t actually know all that much…

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New X-ray free-electron (XFEL) facilities will broaden access to this technology, facilitate methods development, and push boundaries in structural biology.

We first featured XFELs as a Method to Watch in 2011, when this newly established technology promised novel ways of studying macromolecular structure and dynamics. In 2015, we highlighted XFELs' ability to solve high-resolution macromolecular structures from a series of diffraction snapshots of tiny crystals. In 2016, we highlighted the unique abilities of XFELs for capturing very rapid protein structural dynamics.

There are still 'big' reasons why we remain excited about this technology. In 2017, experiments began at the European XFEL in Germany and the Pohang Accelerator Laboratory XFEL (PAL-XFEL) in South Korea. The SwissFEL, located in Switzerland, will begin operating next year. These facilities join the Linac Coherent Light Source (LCLS) in the USA and the SPring-8 Angstrom Compact Free-Electron Laser (SACLA) facility in Japan, which are already in operation.

These new XFELs broaden what has been very limited community access to the technology, allowing more researchers to take advantage of XFELs' unique capabilities. The European XFEL in particular has been long anticipated by many in the structural biology community—not only is it the largest facility, but also it is based on new superconducting accelerator technology that enables it to generate 27,000 X-ray flashes per second—more than 200 times the repetition rate of any other XFEL.

Powerful and ultrafast XFELs enable new approaches to macromolecular structure determination. Image: Kim Caesar/Springer Nature

The unprecedented speed and brightness offered by XFELs are crucial for certain types of experiments. XFEL pulses are so short that data can be collected before radiation damage has time to set in; this is particularly important, for example, for resolving highly radiation-sensitive active site structures of metalloproteins. Speed and resolution are also essential for capturing rapid, minute structural changes in enzymes, for example, that are impossible to detect by other methods. Another exciting application is the potential to resolve structures of single biological particles at room temperature, without crystallization, allowing them to be investigated in very close-to-physiological states.

The incredible features of the European XFEL should allow researchers to push the realm of discovery in structural biology even further. However, clever scientists need to find new ways to harness this power. The current experimental configurations used at LCLS and SACLA do not allow researchers to take advantage of the high repetition rate of the European XFEL; new approaches for sample delivery, data collection, and data analysis will be needed, especially for realizing single-particle structure analysis at high resolution.

We look forward to seeing what researchers in this field will dream up in their quest to discover new biology.

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Yale Team Discovers Way to Pinpoint ‘words’ in Genetic Book of Life

The development of the embryo into trillions of specialized cells is an intricate genetic dance orchestrated by precisely timed expression of genes. Now a team led by Yale scientists have discovered a way to track the precise bits of RNA that that control this crucial process in a living animal.

The new assay, tested on the genome of zebra fish, allows scientiststo pinpoint function of myriad of…

Nature Methods 12, 910 (2015). doi:10.1038/nmeth.3594

Nature Methods 13, 613 (2016). doi:10.1038/nmeth.3944