Caltech’s cryo-electron microscopy helps provide detailed images of coronavirus in race for vaccine

One of the key tools in the race to develop a cure or vaccine for coronavirus stems from techniques developed by a Caltech researcher decades ago.

The images that the public has seen of what exactly the novel coronavirus looks like at the molecular level were made possible in part by the technique.

Caltech biologist Alasdair McDowall is a pioneer in the field of cryo-electron microscopy.

The technique allows scientists to see the most accurate and detailed images of the virus in three dimensions and to examine closely those traits which make it infectious. Vaccine must be precision-built to defeat the virus’ sneakiest and deadliest traits.

“It is crucial to designing a new drug,” says McDowall.  A pioneer in the field of cryo-electron microscopy, McDowall’s findings 40 years ago paved the way for research that went on to win a Nobel Prize for chemistry in 2017.

Previous electron microscope techniques involved a greater degree of altering the cells being studied. As an analogy it was like trying to study the cells of a ripe tomato by looking at sun-dried pieces. It’s just not the same. McDowall found a way of preparing biological matter so it would maintain its life-like state even under a high-vacuum electron microscope. Today it allows researchers to capture highly detailed images of viruses.

“In our cryo-electron microscopy lab we can see the structure of the whole virus inside and outside. This is the beauty of our freezing technology we developed, that we are seeing the whole volume of the virus in three dimensions,” says McDowall.

Today there is an accelerating demand for cryo-EM microscopes around the world and a vigorous effort at Caltech to train people in how to use them.

How do you create a vaccine?

Vaccines harmlessly show viruses or bacteria (or even small parts of them) to the immune system. The body’s defences recognise them as an invader and then learn how to fight it.

Then if the body is ever exposed for real, it already knows how to fight the infection.

The main method of vaccination for decades has been to use the original virus.

The measles, mumps and rubella (MMR) vaccine is made by using weakened versions of those viruses that cannot cause a full-blown infection. The seasonal flu jab is made by taking the main strains of flu doing the rounds and completely disabling them.

The work on a new coronavirus vaccine is using newer, and less tested, approaches called “plug and play” vaccines. Because we know the genetic code of the new coronavirus, Sars-CoV-2, we now have the complete blueprint for building that virus.

Some vaccine scientists are lifting small sections of the coronavirus’s genetic code and putting it into other, completely harmless, viruses.

Now you can “infect” someone with the harmless bug and in theory give some immunity against infection.

Other groups are using pieces of raw genetic code (either DNA or RNA depending on the approach) which, once injected into the body, should start producing bits of viral proteins which the immune system again can learn to fight.

When will there be a coronavirus vaccine?

Research is happening at breakneck speed.

There are more than 20 vaccines in development. One has begun human trials after unusually skipping any animal research to test either the safety or the effectiveness of the vaccine.

Other scientists are at the animal research stage and hope to get the results of human trials later in the year.


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