- August 2, 2022
NASA and CASIS Chase Old Research Paradigms In Orbit
The revolution will not be crystallized: a new method sweeps through structural biology, Nature
“In labs around the world, cryo-electron microscopes such as this one are sending tremors through the field of structural biology. In the past three years, they have revealed exquisite details of protein-making ribosomes, quivering membrane proteins and other key cell molecules, discoveries that leading journals are publishing at a rapid clip. Structural biologists say – without hyperbole – that their field is in the midst of a revolution: cryo-electron microscopy (cryo-EM) can quickly create high-resolution models of molecules that have resisted X-ray crystallography and other approaches, and labs that won Nobel prizes on the back of earlier techniques are racing to learn this upstart method. The new models reveal precisely how the essential machinery of the cell operates and how molecules involved in disease might be targeted with drugs.”
Keith’s note: NASA has been thumping on the value of using the microgravity environment afforded by spaceflight as a way to create large, ultra-pure protein crystals – the kind you need to get the best structural measurements using x-ray crystallography. It was a cool idea with considerable merit. Full disclosure: part of my job at NASA back in the 90s was to promote this type of research and I did so enthusiastically. But it took NASA a long time to actually try this in space while the real world back on Earth pushed ahead.
Now, the ability to use exceptionally small amounts of material on Earth using high-precision, ultra-powerful x-ray sources has allowed materials developed for ground-based crystallography that exceed what is obtained from research using space-based materials. Recently crystallography itself, in its traditional form, is now being eclipsed by new methods that offer even more precise structural information – with no apparent need for the trip to and from space.
So where is NASA in this story?
NASA wants everyone to think that they are poised on the cusp of cutting edge technology in space when it comes to using ISS. That is often the case in some instances, but not in this one. On 30 January 2014 Nature magazine had a series of articles along the theme of “Crystallography Turns 100”. Neither NASA or microgravity/space-based crystallography research are mentioned. Science magazine did a similar feature in March 2016. Again, no mention of NASA or space-based research.
CASIS and the ISS National Laboratory are the ones who have the lead on all of this. Yet they seem to be stuck in a research paradigm that has always been behind the curve. Speeding up access time to ISS has helped – but not in this area of research. They are flying out-of-date technology to an exceptionally expensive research facility and calling it cutting edge. If you try and engage CASIS or ISS National Laboratory folks in a discussion on this topic they just look at you funny. But when they gather the faithful at their annual meetings, its a mutual admiration love fest. More choir practice in an echo chamber – NASA-style.
Perhaps the most bizzarre and irresponsible aspect of this all is that the ISS National Lab and CASIS routinely ignore and steadfastly refuse to post online the weekly SPACELINE Current Awareness research results paid for (since 1999) by NASA. Here is an archive – the only one there is – and it is on my website. What does this say about the capabilities of CASIS and the ISS National Lab when their staff refuses to disseminate their agency’s own research results?
The ISS is an amazing research facility unparalleled in human history with regard to the unique environment it operates in. To be certain, NASA has put some very creative things up there and continues to do so. But when it comes to biotech NASA has (at best) second rate science planners using this resource for stuff that the research community writ large would describe as out dated. When will NASA wake up and realize that it needs to clean house at CASIS and ISS National Laboratory? NASA needs world class staff to run a world class research facility in orbit.
– Science News CASIS Would Rather You Not See, earlier post
– Space Station Science Has Been Left in the Dust – Again, earlier post
– Using the ISS: Once Again NASA Has Been Left in the Dust, earlier post
– Realizing the Research Potential of the ISS Once and for All, earlier post
– While NASA Flies In Circles Technology Advances Back on Earth, earlier post
– One More Reason Not To Use the ISS?, earlier post
Cryo-electron microscopy reconstruction of the bacteriophage phi6 procapsid sliced open to show the four types of protein, NIH Larger image
Near-atomic resolution of protein structure by electron microscopy holds promise for drug discovery, NIH
“Cryo-EM is positioned to become an even more useful tool in structural biology and cancer drug development,” said Douglas Lowy, M.D., acting director, NCI. “Even for proteins that are not amenable to crystallization, it could enable determination of their 3D structures at high resolution.”
Structure of the toxic core of ?-synuclein from invisible crystals, Nature
“Here we describe crystals of NACore that have dimensions smaller than the wavelength of visible light and thus are invisible by optical microscopy. As the crystals are thousands of times too small for structure determination by synchrotron X-ray diffraction, we use micro-electron diffraction to determine the structure at atomic resolution.”