Post-doctoral position: Nanotubular Self-Assembly Driven by Host–Guest Recognition
A one-year postdoctoral position (expected start date: January 2027) is available jointly at the Institut Lavoisier de Versailles (UMR 8180) and the Laboratoire de Physique des Solides (UMR 8502) within the framework of a project funded by the PSINano Paris-Saclay program.
The aim of this interdisciplinary project, situated at the crossroads of supramolecular chemistry, nanoscience, and liquid crystal science, is to design nano-systems inspired by biological microtubules that are capable of dynamic and controlled assembly and disassembly. While most artificial nanotubes lack complexity and adaptability, largely because they are constructed from a single type of building block, the project seeks to overcome this limitation by exploiting tunable host-guest interactions.
In this context, our consortium has recently demonstrated that a naturally occurring chiral macrocyclic sugar can act as a supramolecular “glue” for inorganic polyanionic species in aqueous solution, spontaneously generating supramolecular nanotubes (see Figure). Remarkably, these nanotubes are able to align and self-organize into liquid-crystalline phases, opening new opportunities for the development of adaptive and hierarchically structured materials. Building on these findings, the project pursues three main objectives: (i) establishing the relationships between the elementary building blocks and the structure of the resulting nanotubes or intermediate superstructures, (ii) controlling assembly and disassembly through external stimuli, and (iii) investigating the collective organization of nanotubes, particularly in liquid-crystalline phases.
From left to right/ View of the building blocks needed to build our first artificial nanotubes. X-ray structural model showing the ability of the building blocks to polymerize through non-covalent host-guest association. Cryo-EM images showing the nanotubes with a diameter of 16.5 nm in equimolar solution of building blocks. Small and wide scattering data (neutron and X-ray) showing the typical oscillations (Bessel function) in the low q region, indicating the existence of tubular organization.
The postdoctoral researcher should have a strong interest in the physical chemistry of self-assembling systems, soft matter, and/or host-guest chemistry. The main techniques that will be employed include multinuclear NMR spectroscopy, X-ray scattering, cryogenic transmission electron microscopy (cryo-TEM), and polarized optical microscopy. Experience with one or more of these techniques will be considered a strong asset. In addition, excellent communication and teamwork skills are expected, as the postdoctoral researcher will work closely with three principal investigators from two different laboratories.
Contact: Clément Falaise (clement.falaise@uvsq.fr), Pascale Launois (pascale.launois@cnrs.fr), and Amélie Leforestier (amelie.leforestier@universite-paris-saclay.fr), providing a CV and a cover letter.
_____________________________________
M2 Internship: Chromatin remodelling into a crystal upon spermiogenesis
Spermiogenesis is a radical process of cell differentiation whereby sperm cells acquire a compact and specialized morphology. In many animals, this entails dramatic chromatin remodelling: most histones are replaced by sperm-specific nuclear basic proteins (SNBPs), including protamines. In vitro, protamines, acting as multivalent cations, can organize long DNA molecules (>10kbp) into ~150 nm-wide toroids, and short DNA molecules (<200bp) into crystalline rods with hexagonal order. In situ configuration of the “protaminized” genome in mature sperm is largely unknown, as well as the structural transitions occurring from the initial histone-containing “bead-on-string” chromatin. In this internship, we propose to explore the structural transitions in cricket genome folding along spermiogenesis, focusing on how protamines organize the paternal genome in mature sperm in the two-spotted cricket Gryllus bimaculatus. A precise spatio-temporal dynamics of histone acetylation and the histone-to-protamine transition are critical to achieve this process. In G. bimaculatus, an emerging model organism, it occurs within cysts of synchronous spermatids.
The internship will combine cryo electron microscopy and tomography, polarization microscopy and simulations. We will follow structural transitions during spermiogenesis from the nucleosome bead-on-string chromatin expected in early cysts to the mature sperm cells. Previous studies and preliminary results suggest the entire genome there folds as a nucleus-scale (liquid) crystal.
Supervision: Amélie Leforestier (SOBIO), Guillermo Orsi (Epigenetics and Chromatin, IAB, Grenoble) & Yves Lansac (SOBIO, GREMAN, Tours Univ.).
Level: M2
Start date / duration: Winter-Spring 2027 / 6 months
Contact: amelie.leforestier@universite-paris…
_____________________________________
M2 Internship: Deciphering the structural environment of transcription in situ: interplay between RNA polymerase II and chromatin structure
Eukaryotic genomes are compacted in the nucleus as chromatin, an array of nucleosomes (~147 bp of DNA wrapped around a histone octamer) connected by short linker DNA segments. This bead-on-string structure restricts access to DNA sequences, modulating all nuclear processes, including transcription, a key step of gene expression. In eukaryotes, transcription is catalysed by RNA polymerase II (Pol II). Nucleosomes stand a major energy barrier to Pol II progression, which is associated to partial disassembly and displacements of the particle. Despite many structural studies in vitro, the interplay between chromatin organization and transcription remains poorly understood, especially in situ where the local chromatin architecture during transcription is unknown. We will explore how transcription couples to local chromatin organisation, assembly and disassembly in situ. Using cryo electron tomography (cryo-ET) combined with image analysis and simulations, we aim at characterizing the variety of nucleosome, Pol II and chromatin fold conformations within transcriptionally active regions. We have recently demonstrated the potential of this approach to resolve nucleosome and chromatin folding in situ, and explore their structural heterogeneity in relationship with their functional compartmentalization.
This experimental internship in the field of structural biology includes complete cryo-ET workflow from sample preparation (sample vitrification by high pressure freezing, cryo-sectioning, cryo-CLEM) to cryo-tomogram acquisition on high end instruments. According to the advancement, it will also include first data analyses: tomogram reconstruction & denoising, particle picking & segmentation, sub-tomogram averaging. We dispose of a large set of preliminary data for training and test of data analysis tools.
We are seeking candidates with a background in Cell Biology, Biophysics and/or Physics. Supervision: Amélie Leforestier (LPS) & Mikhail Eltsov (IGBMC, Illkirch).
Level: M2
Start date / duration: Winter-Spring 2027 / 6 months
Contact: amelie.leforestier@universite-paris…
_____________________________________
Deciphering Hepatitus B Virus assembly through machine learning
Hepatitis B is a chronic disease affecting nearly 300 million people worldwide and causing approximately 1 million deaths annually. It is caused by the Hepatitis B Virus (HBV), a 35 nm nanocapsule composed of proteins and lipids that protect the viral genetic code. The virus replicates in infected cells through a self-assembly process, enabling molecular components to form new infectious viral particles. Antiviral molecules that disrupt this self-assembly step are currently under development in laboratories, with some even in clinical trials. However, a mystery remains: How do these molecules disrupt virus formation? What is their influence on its structure and assembly kinetics?
At the intersection of physics, virology, and chemistry, our international consortium (Institut de Biologie Intégrative de la Cellule @ Gif-sur-Yvette, Emory University, University of California Riverside) is able to reconstitute in vitro part of the virus in the presence of antivirals. Using high-resolution X-ray scattering (SOLEIL synchrotron), we capture massive datasets in reciprocal space, which are key to uncovering the nanoscale assembly mechanisms of HBV.
The goal of the internship is to develop a machine learning model capable of decoding the structural parameters of viral particles from their scattering signatures. To achieve this, you will:
– Build a database of particles in the process of assembly using a Monte Carlo code.
– Train an algorithm to reconstruct nanometric morphologies from a Fokker-Planck assembly model, either through regularized regression or recurrent neural networks, depending on performance.
– Test it on recently collected datasets from the synchrotron and interpret the underlying mechanisms regulated by antivirals and/or crowding agents.
The intern should have a strong interest in physical modeling and complex data analysis. Proficiency in Python is required, but specialized libraries can be learned on the job. Finally, a curiosity for the biomedical applications of physics and AI is essential.
Level: M1 or M2
Start date / duration: Spring 2027 / between 3 and 6 months
Contact: Guillaume Tresset
Biomolecular condensates sustained by antagonistic enzymatic activities
A decade of research has focused on membrane-less organelles, also known as biomolecular condensates, which play a key role in many essential cellular functions. These condensates facilitate biochemical reactions involved in metabolism, homeostasis, stimulus response, as well as pathological processes such as fibrillation or viral production. Unlike membrane-bound compartments, their formation can be described as a phase separation within the active environment of living cells. The chemical reactions occurring within them consume « fuel » (such as ATP) and release « waste, » maintained by external mechanisms, thus placing the system in a non-equilibrium state. Their physical behavior deviates from classical predictions, exhibiting counterintuitive phenomena such as blocked growth or spontaneous scission.
Although cellular condensates typically contain dozens of distinct proteins and RNAs, it is possible to reconstitute in vitro condensates that closely resemble native intracellular bodies using only short peptides and polyuridine RNA. This reductionist approach has improved our understanding of the microscopic forces and « molecular grammar » underlying phase separation. A major breakthrough is that these polypeptides can be modified to serve as substrates for kinases, enabling dynamic regulation of phase behavior in vitro through phosphorylation. By exploiting this mechanism, condensates can be reversibly assembled and disassembled using a pair of enzymes (kinase/phosphatase). This property is particularly significant as it reproduces the phosphorylation-mediated regulation observed in vivo during cellular phase separation.
In this project, we will explore the dynamics of biomolecular condensates sustained by the antagonistic activities of kinase and phosphatase, mimicking the intracellular environment. A fluidic device will be fabricated using 3D printing and adapted to a confocal microscope to study how active processes modulate the formation and dissolution of condensates. Numerical simulations, based on a simple model of phase separation under active conditions, will help interpret the experimental data. These unprecedented measurements will reveal the liquid-like properties of model condensates under conditions close to those of the cytoplasm.
Level: M1 or M2
Start date / duration: Spring 2027 / between 3 and 6 months
Contact: Guillaume Tresset