The general objective of our laboratory is to understand in molecular details the epigenetic functions of nuclear Argonaute proteins and their associated small RNAs in animals.
We are using C. elegans as a model system to test the hypothesis that nuclear Argonaute proteins and their associated small RNAs constitute an RNA-based epigenetic system for propagating the memory of the transcriptional status of the genome during cell division or across generations.
Specifically, we are investigating:
C. elegans is an excellent model system to systematically address these questions.
WHY C. elegans?
C. elegans is suitable to a combination of traditional genetic and RNAi screens, molecular biology, and high-throughput genome-wide analyze
The developmental program is understood at the single-cell level
It has been used extensively as a model for understanding the mechanistic response to environmental changes and how animals respond to different biotic and abiotic stresses.
RNAi and transgenerational epigenetic phenomena are well known
The genome-wide map of epigenetic modifications that occur during the C. elegans development are mapped
The short life cycle and ability to grow large isogenic populations of worms allow for the study of multigenerational epigenetic effects readily
We are integrating genetic, biochemical, and molecular biology tools with established high-throughput genomic and proteomic approaches to achieve a deep mechanistic understanding of the role of Argonaute-bound short RNAs in epigenetic inheritance in animals.
We employ a wide range of cutting edge techniques to study chromatin and epigenetic regulations, which include:
- Global Run On sequencing (GRO-seq)
- short RNAs and mRNAs sequencing (RNA-seq)
- Chromatin immunoprecipitation sequencing (ChIP-seq)
- Ribosome profiling (Ribo-seq)
- Genome-wide mapping of nucleosome positioning (MNase-seq)
- individual-nucleotide resolution Cross-Linking and ImmunoPrecipitation (iCLIP)
- Chromatin Isolation by RNA Purification coupled with mass spectrometry (ChIRP-ms)
The Institut Pasteur has a long-standing history of excellence in science and is providing an excellent scientific environment with experts in the fields of molecular, developmental, and computational biology, and state-of-the-art core facilities, including proteomics, high throughput sequencing, and imaging technologies.
Our research has the potential to significantly advance our understanding of the molecular mechanisms underlying epigenetic inheritance and reveals their impact on animal development and adaptation to changing environments.