Description du sujet de thèse

NANOLIFE - At the interface of chemistry, geology, and biology: Do natural nanostructures promote the oligomerization of nucleotides and the formation of DNA and RNA strands?
One of the great mysteries of prebiotic chemistry concerns the appearance of polynucleotides, the molecular carriers of the genetic code. Life depends on the formation of simple organic building blocks such as nucleobases and nucleotides, which can form in a "primitive soup." However, the polymerization of these building blocks into nucleic acids (DNA, RNA) remains mysterious, as it cannot occur in an abiotic environment without enzymes. How can this energy barrier be overcome?
Role of Mineral Surfaces - Preliminary Results:
The oligomerization of nucleotides on the surface of clay minerals is a long-studied hypothesis, but the molecular mechanisms remain poorly understood. Nanominerals, by creating confined environments, could promote oligomer formation through over-concentration. Imogolites, natural nanotubes present in volcanic soils, are particularly interesting. Their outer layer of aluminum oxyhydroxides allows interactions with organic acids and phosphate groups, promoting the adsorption of monomers and potentially catalyzing the formation of oligonucleotides.

Recent work has shown that a covalent bond forms between the surface of imogolites and the phosphate groups of nucleotides, revealing surface reactivity superior to that of clays (Rose et al, in prep). However, the formation of oligonucleotides on nanotube supports remains unanswered. Other preliminary results indicate that di- and tetranucleotides can form from nucleotide-lipid aggregates. Is this amplified in the presence of imogolite?
Objectives
This PhD topic aims to explore the oligomerization of nucleotides and nucleo-lipids on surfaces by studying whether imogolites can activate the phosphate group and form oligonucleotides under prebiotic conditions. Various parameters will be modulated to promote the appearance of biopolymers, particularly the structural and surface properties of imogolites (hydrophilic or hydrophobic surfaces, creation of structural defects, incorporation of trace metals, etc.). The candidate will seek to understand the formation of oligonucleotides after 1) adsorption of monomers on nanometric support and if 2) organic nanovesicles promote, through confinement, the interactions between mineral surfaces and nucleotides.
Méthodology
The candidate will synthesize imogolites and conduct adsorption experiments with different nucleotides, nucleotide-lipids, and oligonucleotides. They will use separation and characterization tools such as ultrafiltration, UV-Vis spectroscopy, circular dichroism, high-resolution mass spectrometry, liquid NMR, Zeta potential, solid NMR, FTIR, and XAS on synchrotron radiation to examine the nanotubes and the structure of surface complexes.

We are looking for a motivated candidate with a strong interest in interdisciplinary projects. The required profile is as follows:
Knowledge
 Manage and solve problems in various fields of organic, inorganic, and/or physical chemistry
 Understand the basics of the structure of matter and the reactivity of chemical systems
 Organic chemistry, stereochemistry, properties of major functions
 Inorganic chemistry, elements, and properties - structure of edifices
 Thermodynamics, solution chemistry, kinetics
 Coordination chemistry and inorganic chemistry
 Respect scientific ethics
 Analyze, interpret experimental data, develop arguments, and write a synthesis report
 Master practical knowledge and technologies related to the discipline: implement and carry out an experimental approach autonomously, use the most common measuring devices and techniques, identify sources of error, analyze experimental data and consider their modeling, validate a model by comparing its predictions with experimental results, appreciate the limits of validity of a model

Operational Skills
o Physico-chemically characterize substances
o Use the main identification and analysis techniques: spectroscopy (IR, UV, visible, NMR, etc.) and separation techniques, mass spectrometry, etc.
o Use the main synthesis and purification techniques
o Acquire skills in observing, analyzing, and describing technical and chemical systems
o Know how to verify and implement various regulations regarding hygiene and safety

Contexte de travail

The project benefits from expert partners, including CEREGE, a pioneer in the study of environmental nanomaterials, and ARNA, specialized in bio-organic chemistry and nanotechnologies. An international collaboration with Duke University (Department of Civil and Environmental Engineering, M. Wiesner Group) will explore the role of nanometric vesicles associated with imogolites in promoting the oligomerization of nucleolipids. Additionally, Duke University coordinates an international project INFRAMES (International Network For Researching, Advancing, and Assessing Materials for Environmental Sustainability), which will support the mobility of the PhD student between France and the USA.

CEREGE is located on the Petit Arbois plateau, Technopole Environnement Arbois-Méditerranée, Avenue Louis Philibert, Les Milles-Aix-en-Provence