Lignocellulosic biomass offers great opportunity to develop sustainable polymeric materials with functional properties. Polyfurfuryl alcohol (PFA) is a thermoset resin obtained from polycondensation of furfuryl alcohol – a biobased platform molecule. Humins which are co-produced from biorefinery operations form a macromolecular furanic network that could be valorized into thermoset applications. However, both PFA and humins after thermal curing are relatively brittle due to their high cross-link densities. Therefore, the FUTURES project aims at tailoring the structure and properties of both PFA and humins in order to foresee new domains of application for these biobased polymers. The idea is based on the intrinsic capacity of furans for ring opening leading to the formation of flexible chains containing ketonic entities within the macromolecule. An optimal balance will be found to create sufficient open structures while keeping the advantage of the remaining furanic entities. The reactivity of the ketonic groups will be exploited to generate new functionalities or properties.

Proteins and nucleic acids are functional biopolymers composed of L-amino acids and D ribose subunits that break chiral symmetry. The origin of the symmetry-breaking event is unknown. The photochemistry model by which circularly polarized light (cpl) can induce an enantiomeric excess (e.e.) in organic molecules has recently been strengthened by the observation of cpl in the star-forming region of Orion and the detection of photochemically produced organics in cometary ices by the Rosetta-Philae mission. The ‘Amino Acid Asymmetry’ (AAAs) project proposes to characterize chiroptical properties of chiral amino acids and their volatile aldehyde precursor molecules for the first time in the gas phase, where the initial asymmetric interactions between chiral photons and life’s molecular subunit precursors are assumed to occur. Gas phase circular dichroism (CD) and anisotropy spectra of amino acids have never been recorded. A special gas cell will be developed that will allow us to generate CD and anisotropy data. The gas cell, with a 500 mm optical path length, will operate in the range from the vacuum ultraviolet to the visible. The gas cell will be pressure-controlled and can be heated up to 200 °C to allow for a sufficient amino acid gas phase density. CD and anisotropy spectra of amino acids will be systematically studied in the gas phase at the Danish synchrotron facility ASTRID2. After recording the amino acid chiroptical data, we will expose amino acids in the gas phase to circularly polarized synchrotron radiation at the DESIRS beamline of the synchrotron SOLEIL in France. The asymmetry of the chiral photons will be transferred to racemic amino acids in the gas phase. After condensation of the gas-phase irradiated amino acids, the samples will be analyzed for the determination of the induced enantiomeric excess. These analyses will be performed by using enantioselective multidimensional gas chromatography at the University Nice Sophia Antipolis. Furthermore, we will simulate the photochemical and low-temperature/low-pressure interstellar formation of pristine organic molecules: Amino acids will be photo-chemically formed from C1 and N1 reactants such as methanol, ammonia, and water by using circularly polarized synchrotron radiation at the DESIRS beamline, SOLEIL. Reactants will be 13C-labeled to distinguish the photochemical products from contaminants. The AAAs project will investigate and characterize the asymmetry transfer from chiral photons to pristine chiral organic species. Data will be employed to decipher the asymmetric origin of functional biopolymers. The results obtained on the origin of the chiral molecular building blocks of life, i.e., amino acids and ribose sugars, will be interpreted using our data from both the ongoing cometary Rosetta-Philae mission and the scheduled ExoMars mission. AAAs coordinator Meierhenrich is co-investigator in both missions (COSAC and MOMA). Through the combination of laboratory with space data (comet and Mars), the AAAs project aims to decipher the asymmetric origin of life on Earth.

The PFPImaging project describes the milestones and the collaborations needed for the synthesis of fluorescent fluorogenic probes for a better super-resolution imaging of cellular targets. The state of the arts describes the existent methodologies and their insufficiencies. PFPImaging answers to the described bottlenecks when following specific research blueprints. The new blinking probes are specific, more bright and exquisitely tuned and adaptable for the super-resolution imaging of nucleic acid and protein targets. The collaborations are describing the expertise of each partner: e.g. fluorescent nucleic acid chemistry for the project leader and molecular photo-physical detection and imaging in vitro and in cellulo. We likewise pursue the aim to considerably improve the visualization of cellular tubulin to confirm our new tool’s performances. In the future, these new tools the method is generalizable to the observation of proteins and nucleic acids of cytoplasm, nucleus and other cellular compartments.

Drosophila suzukii is an invasive species causing severe damages to the fruit industry in Europe and North America. Indeed, in contrast with other drosophilids that exclusively target decaying fruit, D. suzukii has evolved a preference for laying eggs in ripening fruit, precipitating their decay. D. suzukii is one of the most important pest insect in Europe, that target a broad range of fruit species, and for which we have no efficient control strategies. We have previously established that the egg laying on ripening fruits is mediated by olfactory cues. The goals of this project are (1) determining which fruit odors elicit egg laying in D. suzukii, (2) identifying the Olfactory Receptors sensing these odors, and (3) identifying novel ligands for these receptors that can be used in integrated pest management strategies. To achieve these goals we will combine analytical chemistry, computational modeling, and neurogenetics and genome editing technics that we have developed for D. suzukii.

There is currently an urgent need for new antibiotics in order to overcome the steady emergence of multidrug-resistant bacteria and the associated human and economic cost. For the development of new antimicrobial agents, two major issues must be overcome: the difficulty to permeate bacterial membranes and the toxicity of compounds. Furthermore, the available number of specific targets remains restricted. All these issues led to a strong decrease in the efforts done toward the discovery of new antibiotics both in industry and in academia. In this context, the purpose of this project is the discovery of new antibiotics targeting original and so far unexploited targets: bacterial toxin-antitoxin (TA) systems. TA systems are small genetic elements composed of a toxin gene and its cognate antitoxin both coding for corresponding toxin and antitoxin products. The toxins of all known TA systems are proteins able to inhibit bacterial cell growth or lead to cell death, whereas the antitoxins are either proteins or small regulatory RNAs that neutralize the toxin. Here, we decided to target type I TA systems where the antitoxin is a non-coding RNA that binds to the messenger RNA (mRNA) coding for the toxin thus inhibiting its translation. In order to validate the proposed strategy, we propose to target a particular type I TA system of the major human gastric pathogen Helicobacter pylori which is a gram negative bacterium infecting about 50% of the entire world population. We recently discovered a new family of type I TA systems in H. pylori called AapA/IsoA systems whose regulation relies on a double kissing-loop interaction between the AapA toxin mRNA and the IsoA antitoxin RNA. This TA system is present in multiple copies on the chromosome (multiple loci) of this bacterium. A small molecule that would be able to inhibit the interaction between the antitoxin and the mRNA of the toxin at these multiple loci could turn on the expression of several bacterial toxins thus leading to bacterial cell death. Also, we recently demonstrated that the inhibition of this system by the aminoglycoside neomycin leads to the activation of the toxin synthesis. Based on our experience about the design and the synthesis of selective RNA ligands, a large library of new compounds constituted of various known RNA binding domains will be prepared using a multicomponent synthetic methodology. The synthesized compounds will be evaluated for their ability to disrupt the loop-loop interaction between the antitoxin and the toxin mRNA using in vitro assays. Their biological evaluation in bacterial cultures will also allow for the study of (i) their ability to induce toxin synthesis, (ii) their antimicrobial activity, (iii) their ability to penetrate inside bacteria and eventually (iv) their toxicity against eukaryotic cells. The most active compounds will be finally optimized thanks to the proposed highly versatile synthetic methodology in order to improve their biological activity and their pharmacodynamic/pharmacokinetic properties toward in vivo studies. It is important to note that compounds bearing activity as inhibitors of toxin-antitoxin systems would be not only interesting therapeutic tools for antimicrobial development, but also biochemical tools toward a better understanding of toxin-antitoxin systems mechanisms that remains still largely unknown. The expected results of this project are (i) the identification of new RNA ligands targeting loop-loop complexes formation and (ii) the development of an innovative antimicrobial approach by turning on the expression of TA systems toward the eradication of bacterial infection. In conclusion, we present here an original approach toward the validation of TA systems as promising antimicrobial targets and potentially the discovery of new antibacterial compounds against H. pylori infections. The same approach could be further applied to other major pathogens such as Staphylococcus aureus and Mycobacterium tuberculosis.