Sparking a revolution in structural biology

In the early 1980s, EMBL Heidelberg Group Leader Jacques Dubochet and technician Alasdair McDowall discovered that flash-freezing proteins in liquid ethane could preserve their structure during microscopy – a process called vitrification. It was a critical advance that laid the groundwork for the rise of cryo-EM and brought Dubochet and two other scientists the Nobel Prize in Chemistry in 2017.

Today, cryo-EM is game-changing, enabling large molecules to be imaged quickly and facilitating the development of new drugs and vaccines. Scientists from around the world have used cryo-EM to determine virus structures responsible for some of the world’s greatest disease threats, such as hepatitis B and C, Zika, dengue, and tick-borne encephalitis. In 2020, cryo-EM also yielded precise images of the virus that caused COVID-19, assisting vaccine development.

Pioneering tools that improve research for all

Scientific breakthroughs are often only made possible through innovative technological developments. And EMBL Grenoble’s scientists are extremely deft at technological improvements that – for example – make beamlines and synchrotrons work even better. It’s why the partnership between EMBL Grenoble and the European synchrotron, ESRF, has played a significant role in developing and advancing cutting-edge crystallography technologies used in biosciences and medical research. By collaborating with the manufacturer Arinax, researchers and engineers from EMBL Grenoble helped commercialise this pioneering instrumentation and automate the entire sample-handling process.

The inventions include micro-diffractometer devices, which enable automated, high-precision positioning of protein crystals in an X-ray beam, significantly increasing the efficient use of beamtime at synchrotrons. As of 2021, Arinax had installed micro-diffractometers in over 15 synchrotrons around the world. The ability to adjust technologies to researchers’ needs is just one reason why instruments developed at EMBL are – and will continue to be – widely used by the scientific community.

In the 20th century, the world battled three influenza pandemics: in 1918, 1957, and 1968. Since then, molecular biology has made important strides in understanding these RNA-based viruses. Beyond viruses, RNA is central to many fundamental processes in the cells of living organisms. Unsurprisingly, the  breakdown of RNA-related processes is therefore associated with a myriad of  diseases, emphasising the importance of understanding the complex biology of RNAs. 

EMBL – since the mid-1980s – has been at the heart of advancing RNA research, contributing significantly to unravelling the complexities of RNA-mediated biological mechanisms. Specifically, EMBL’s structural biologists provided insights into the biology of RNA-based viruses such as the influenza virus, opening new doors to structure-based anti-influenza drug design that ultimately created Savira Pharmaceuticals, a company dedicated to identifying and developing effective anti-influenza drugs. 

This kind of research also demanded the progression of state-of-the-art techniques at EMBL, such as cryo-EM, to see the molecular mechanisms behind RNA’s participation in essential cellular processes in unprecedented detail. During the recent SARS-CoV-2 pandemic, EMBL research helped better understand this RNA-based virus. Studies using cryo-EM, for example, enabled scientists to understand important structures of this virus to develop effective COVID-19 vaccines. Additionally, EMBL RNA research over the decades has been fundamental to our current understanding of RNA-splicing mechanisms, nuclear-cytoplasmic transport, mRNA translation, RNA stability, and intracellular transport. More recently, EMBL scientists spearheaded the discovery of RNA binding proteins and riboregulation.