Engineering artificial organelles in cells: intracellular phase transition and pathological RNA granules
Internship title: Engineering artificial organelles in cells: intracellular phase transition and pathological RNA granules
Name: Department of Chemistry – ENS
Affiliation: UMR8640 – Department of Chemistry – Ecole Normale Supérieure
Address: 24 Rue Lhomond
Name: Zoher GUEROUI
Phone number: 0144322409
Name: Zoher GUEROUI / Audrey COCHARD
Phone number: 0144322409
Subject Keywords: Synthetic Biology, RNA, Liquid Liquid Phase Separation, Protein engineering, “Omic”
Tools and methodologies: Protein/RNA engineering, Cell Biophysics/biology, Quantitative Optical Microscopy/Imaging, Single Molecule FISH
Summary of lab\’s interests: We use interdisciplinary and quantitative approaches to study some aspects of biological systems
Current research projects include:
1. Self-organization of biological systems (Intracellular Phase Transitions, Reaction Diffusion processes, …)
2. The engineering of microorganisms as programmable factories to implement genetically-encoded functions, or to produce nanomaterials.
These projects benefit from several key collaborators based in France (Biologists at IBENS / SU / Collège de France) and in Japan (CiRA, Kyoto University). The Laboratory is developing interdisciplinary research between Biophysics, Biology, and Synthetic Biology. The Master student will benefit from strong preliminary experiments.
Project summary: Membrane-less organelles are ubiquitous functional sub-units of cells that are involved in many vital functions such as RNA regulation, shaping the general gene expression output. Importantly, their dysfunction is linked to viral infection, cancer, and neurodegenerative diseases. For instance, the solidification of RNA-protein membrane-less organelles into toxic aggregates have been associated to pathological diseases such as amyotrophic lateral sclerosis (ALS). Beyond their molecular composition, these organelles are very complex regarding their biochemical and biophysical properties, which implies the development of novel tools for their study.
By combining chemical biology, biophysics and cell biology, our team has recently developed a novel methodology to form artificial membrane-less organelles, within living cells, with tunable biochemical and biophysical properties (Garcia-Jove et al, Nat.Comm 2019). The engineered synthetic granules succeed in recapitulating the intracellular phase transition process that control the formation of RNA-protein granules. We also found that our approach can be extended to study membrane-less organelles in human cells including iPSC, neurons.
The outputs of the master project are multiple and original: (1) Expanding our toolbox for inducing the assembly of artificial organelles with fine-tuned properties cells. (2) Towards the study of pathological granules in neurons: spatiotemporal dynamics and transcriptomic/proteomic of pathological organelles (neurodegenerative diseases).
Interdisciplinary aspect of the project: Tools and concept from Synthetic Biology, Biophysics, Cell biology