π Health and biotech π Science and technology

Biomolecules: three techniques at the cutting edge of research

3 episodes

1

Cryogenic electron microscopy: the resolution revolution?
2

Quirky RNA to combat SARS-CoV-2
3

How can we monitor dynamics of biomolecules in real-time?

Épisode 1/3

Cryogenic electron microscopy: the resolution revolution?

Pierre-Damien Coureux , Assistant Professor in Electron Microscopy at BIOC* at École Polytechnique (IP Paris)

On April 20th, 2022

5 min reading time

Pierre-Damien Coureux

Assistant Professor in Electron Microscopy at BIOC* at École Polytechnique (IP Paris)

Key takeaways

Modern structural biology was born in the 1950s with the first publication of the DNA double helix structure and the first structures of proteins, which were awarded two Nobel prizes in 1962.
Although the first electron microscopes existed well before the 1950s and made it possible to observe materials at high resolution, for a long time the molecules of living organisms remained difficult to observe with this technique. In biology, this structural approach was thus often considered to be a big magnifying glass.
Over the last ten years or so, the technique has made revolutionary advances, allowing molecules to be seen at the atomic scale and as small as haemoglobin.
If Covid had appeared 15 years ago, researchers would never have been able to obtain its structure so quickly.
The next challenge is to see the interior of cells in sufficient detail to locate all the known atomic models of life and to understand their interactions.

Épisode 2/3

Quirky RNA to combat SARS-CoV-2

Jean-Louis Mergny, Inserm Research Director and Head of the Biology Department at IP Paris

On April 20th, 2022

4 min reading time

Jean-Louis Mergny

Inserm Research Director and Head of the Biology Department at IP Paris

Key takeaways

Many avenues for better treatments to treat coronavirus have emerged, but mainly doctors have also made huge strides in terms of early detection of patients and intensive care protocols.
Targeting a virus is very difficult, as we have seen with the slow development of effective treatments for HIV or hepatitis.
However, a clinical lead has opened up with the promising effects of a protein known as NSP3, which blocks virus proliferation.
Developing a drug candidate is nevertheless a long process, and a treatment proposed by Jean-Louis Mergny has started the preclinical phase in rodents to first assess their distribution and possible toxicity in vivo.

Épisode 3/3

How can we monitor dynamics of biomolecules in real-time?

On April 20th, 2022

3 min reading time

Pascale Changenet

CNRS Research Director in biophysics at Ecole Polytechnique (IP Paris)

François Hache

CNRS Research director and Professor of Physics at Ecole Polytechnique (IP Paris)

Key takeaways

Changes in the helix structure of proteins and DNA can happen in a few tens of femtoseconds (10 x 10-15 seconds). With such a short time window, observing such processes remains an experimental challenge.
Chirality is an important component of life. A molecule is chiral when it is not superimposable with its mirror image, meaning that the same molecule can have two possible shapes.
The technique known as circular dichroism plays on these 'chiral' shapes, which absorb polarised light in different ways. This can be used to create a unique signal for each possible conformation – like a barcode – to trace changes in its conformations over time.
With advances in AI, it is becoming possible to reliably predict the 3D structure of proteins from their sequences, notably with the new Alpha Fold 2 algorithm.
Understanding the effects of the interaction of certain molecules targeting DNA on its structure is an avenue to be explored for new research in pharmacology or medicine.

Contributors

Pierre-Damien Coureux

Assistant Professor in Electron Microscopy at BIOC* at École Polytechnique (IP Paris)

After a PhD in structural biology on myosin molecular motors at Institut Curie in 2004, he left for the United States to study bacterial and plant photoreceptors using several approaches including electron microscopy. He was recruited in 2008 at the Ecole Polytechnique and works mainly on the cellular machines that synthesise our proteins: the ribosomes, with those of the Archaea as a study model. He was appointed head of CIMEX in 2020 and is also involved in teaching biology at X.

*BIOC: a joint research unit CNRS, École Polytechnique - Institut Polytechnique de Paris

Other contributions

Cryogenic electron microscopy: the resolution revolution?

Jean-Louis Mergny

Inserm Research Director and Head of the Biology Department at IP Paris

A graduate of Ecole Normale Supérieure (Paris), Jean-Louis Mergny completed his PhD on the roles of nucleic acids followed by post-doctoral position in Basel, Switzerland. In 2009, he moved to the Institut Européen de Chimie Biologie (IECB) in Bordeaux where he was later appointed director. At the end of his 10-year term at IECB in 2020, he moved on to continue his research projects at the LOB (*a joint research unit CNRS, École Polytechnique - Institut Polytechnique de Paris, Inserm) in the Paris. The Covid crisis incited him to reorient my research projects towards pathogens with the aim of developing new therapeutic approaches against viral infections. He was appointed Head of the Biology Department at the Institut Polytechnique de Paris in September 2021, and became Co-Head of the " Engineering for Health " Interdisciplinary Center (E4H* https://www.ip-paris.fr/en/research/interdisciplinary-centers/e4h) in 2022. Co-author of over 300 original articles, he has collected over 41,000 citations according to Google Scholar.