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Scientific and medical challenges

DNA, RNA, amino acids, fat, oils, sugars, protein, vitamins, toxins, trace elements… Very familiar and yet mysterious, these terms refer to molecules of living organisms. They are the basic building blocks of biological systems.

Finding out what their structures are, their dynamics, interactions, assemblies and transformations is essential for understanding how the living organism works, for being able to predict or imitate it and, if necessary, for acting on it to cure or harness its potential at industrial scale.

Molecules, molecular assemblies, metabolic circuits: understanding, modeling, predicting, and imitating

Representation in ribbons of the protein nsp9, in the form of a dimer at its only alpha helix and positioned on its surface representation

Representation in ribbons of the protein nsp9, in the form of a dimer at its only alpha helix and positioned on its surface representation. Two nsp9 cristals are also visible on a SARS coronavirus background observed under an electron microscope.

Research conducted within this Institute’s remit seeks to describe:

  • the structure and dynamics of the molecules in a living organism, isolated or combined in complexes;
  • the molecular mechanisms of recognition and interactions which lead to the formation of complexes;
  • the chemical or biochemical transformations of these molecules or complexes;
  • their functions, i.e. their roles in the functioning of a cell or organism and the way they are regulated.

These analyses allow for the:

  • quantification, modeling and prediction of the biological phenomena studied;
  • adjustment of biological functions, for example by modifying the molecules of a living organism, imitating and/or assembling them artificially.

These studies are involved in a wide range of research fields.

Determining the three-dimensional structure of components in living organisms

For example, the structure of a protein or protein assembly is an essential piece of data for rationally designing molecules able to stop it carrying out its role. If the protein examined plays a specific role in a disease, this type of study can result in drug identification. Accordingly, the atomic structure of ribosome, an enormous cell machinery required for gene expression, sheds light on how many antibiotics act on the way it works and on how to improve them. Such research ultimately makes it possible to prevent the resistance mechanisms which are swiftly developing, particularly in intensive care units.

Series approaches and system biology

To understand a given biological function, we therefore need to take account of a series (also called network) of interactions and reactions between biomolecules which are precisely coordinated. This is one of the aspects of "systems biology", i.e. the integration of a series of data for a quantitative analysis of biological phenomena. We can thus understand how the disturbance triggered by a disease disrupts the chain of events in question and can recommend new therapeutic approaches.

Molecules imitating the living organism

Developing molecules that imitate those in the living organism, albeit modified, is very useful in various types of application such as "molecular" imaging approaches, for a clearer vision of and insight into the living organism, or medical imaging or diagnostic tests for better prevention and treatment of diseases.

Toxicology and identification of harmful compounds

To characterize the presence of harmful compounds, sometimes in trace state and often unknown, which either originate from drugs or our environment, as well as study their biological effects, original approaches need to be developed from several disciplines making up "toxicology". This is now a key challenge for society, and is a field in which major efforts are under way, particularly through the French Environment Forum and new, highly demanding European directives, such as the REACH regulation (Registration, Evaluation, Authorization and Restriction of Chemicals), a control system intended to manage the environmental and health risks of chemicals more effectively.

Deciphering of energy mechanisms

The study of chemical reactions involved in biological processes particularly involves understanding energy transformation mechanisms. In the case of photosynthesis, i.e. the transformation of light energy into chemical energy by plants, the aim is to harness the extraordinary effectiveness of this natural phenomenon. Precisely characterizing the biological molecules involved and chemical reactions in play could certainly pave the way towards developing more effective solar panels than we can currently find on the market, imitating natural phenomena, or towards manufacturing biofuels (such as biohydrogen), by taming the processes of the living organism.

Molecular machines

In the foreground, a model reproducing the icosahedral symmetry of the rotavirus capsid.

In the foreground, a model reproducing the icosahedral symmetry of the rotavirus capsid. In the background, reconstruction of the structure of a whole rotavirus by combining radio crystallography and electron cryomicroscopy.

Characterizing biological "motors", i.e. proteins using energy (often chemical) that is naturally available to produce a mechanical force, gives us a deeper understanding of the different types of biological function, from DNA replication to protein transport. But it is also a source of inspiration for developing artificial "molecular machines". To give an example, it is thus planned to produce "molecular computers" for storing and processing information at molecular level.

Reduction of industrial risks and sustainable development

Today, biological components are used to produce all chemical industry reactions and reduce the polluting, toxic and hazardous effects of the chemical industry as far as possible. This is the very basis for a "green" chemical industry.

The three examples above fall within the field of "synthetic biology", i.e. the production of an artificial system with a given function, from naturally existing biological elements.

How are the structures and functions of the living organism studied? A multidisciplinary and integrated approach

Such research requires combined approaches, resulting from different disciplines: biology, chemistry, engineering sciences, computer technology, physics and maths. Cutting-edge tools therefore need developing for part of this disciplinary field for an ever more detailed and relevant analysis of the building blocks making up living organisms. These approaches can be compared to the development of "molecular glasses" for seeing and studying them close-up, as well as, within a broader field, for integrating them in the cell or in such biological fluids as blood, in the same way as an optical zoom would do.

Molecular structure of alpha-N-acetylgalactosaminidase of the Elisabethkingia meningosepticum bacterium in complex with the NAD+ cofactor (in yellow) and the antigen A present on the surface of type A red blood cells. In red, the known alpha-N-acetylgalactosamine molecule hydrolyzed by the enzyme.

Molecular structure of alpha-N-acetylgalactosaminidase of the Elisabethkingia meningosepticum bacterium in complex with the NAD+ cofactor (in yellow) and the antigen A present on the surface of type A red blood cells. In red, the known alpha-N-acetylgalactosamine molecule hydrolyzed by the enzyme.

Biophysical approaches enable "images" of molecular functioning to be obtained, from the atom level to more integrated levels like complex cellular machines. Progress made in detection methods now provides researchers with information on a single molecular structure, and not a population, as well as on its local dynamic transitions.

Molecular modeling undertakes to gather together data on the chemical, structural and dynamic properties of biomolecules with a view to producing models of their functions and interactions.

Biochemistry involves monitoring, understanding and analyzing all the transformations that occur in a cell, for example energy generation, molecule production, damage repair and waste elimination.

Chemistry for living organisms seeks to imitate molecules or biological reactions and therefore provides tools for studying biological functions or drugs that thwart a pathological function. Biophysical and biochemical information is also often necessary for understanding the way in which drugs act and for designing or identifying new active molecules.

Biomathematics concerns the dynamic or quantitative modeling of biological systems.

Lastly, the bioinformatics approach is a key, cross-disciplinary aspect of all this research, involving both "mining" (simulation of a property) and the prioritization of high-throughput analyses and the ad-hoc processing of innumerable amount of data acquired by hi-tech systems.

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