Covid 19th Vaccine The Technology that made it possible

Jason Mclellan an associate professor of molecular biosciences at university of Texas at Austin , have been studying spike proteins of  other coronavirus for half his career, his team has helped established the molecular basis for the spikes function: to attach itself tot he host cell membrane, allowing the virus to hijack the cell, they also figure out how to insert prolines, rigid amino acids  into the spike to halt this portion. Resulting in a spike protein stable enough to be used in a vaccine. It was a few years of research to determine that these amino acids could be inserted  and make it stable enough to become a vaccine.

The Development

It was within 30 days of the genome sequence being published by Chinese researches that we had already determine the structure of the proline stablished SARS-Cov2 spike, Mclellan says 4 of the 5 leading vaccines agains SARS-Cov2 currently in production, rely on his team proline strategy. And they develop that strategy with the help of microscopy tech in the form of the direct electron detection camera, or DED. Before 2010 the development of DEDs, most of the relevant features of those spikes were obscure hidden even from the world’s most popular cameras..The leading techniques for visualizing things as small as cell machinery was x-ray  chrystallography , which bounces x ray photos of the  crystaillized versions of molecules. And interprets the structure based on where they land.  Its an excellent strategy for molecules that are amenable to the crystallization process. Moreover, many proteins like the coronavirus spike, have flexible parts that hinder crystal  formation.

Protein Crystallization

The earliest proteins that crystallized, like DNA, are ones that are very stable. They don’t have any parts that are too floppy, explains Vassar College research team. Proteins DNA, they are inherently flexible. Some proteins can crystallize despite having some places that are disordered, and so in your data, chunks are missing. Some can crystallized at all. Another technique that was originally the run it up to x ray, chrystallography in many researches eyes, was cryogenic electron microscopy  (cryo-em), which fire electrons at flash-frozen samples and calculated their shape, from the scatter electron. Electrons can severely damage biological samples, so only very low doses were allowed. Making images noisy , like photographs taken with too little exposure. The scattering of electrons was recorded either on film, or, later, on charge-couple devices  (CCDs), which store date in pixels, like digital cameras do. If data was captured on film, they have to be converted to pixels before they could be fed into a computer for processing. Or to protect the silicon in CCDs, this method requires something called a glass scintillator. But the glass limited the final resolution of the image.

The cryo-em revolution

The cryo em field, kick for a period of  “resolution revolution”. The first commercially DED camera was 2008′ DE12 from direct electron in sand Diego , as sensor technology improved, the DED12 was quickly follow by the DE16  and DE64, as well as competing model from Gatan and the FEI company. The sudden availability of these multimillion dollar cameras, conviNced many crystallographers to finally switch over and join the cryo-EM team.

Designing the vaccine

In 2019 after year of contributing to vaccine research from Dartmouth Mclellan moved his lab from New Hampshire, to UT Austin to have access to a DED, for his work on Coronavirus spikes which have resisted all attempts at crystallization. Using the Gatan k3, one of  four DED cameras on the market today, Mclellan team was able to capture key stages of the spikes functions. This intimate view of it in motion allow them to design a vaccine- stable version of the spike protein that could confer immunity without risking infection. By 2020 cryo-EM had reached atomic resolution . “You can see the hydrogens on the amino acids. “Says Mclellan. Really amazing!

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