The general objective of our laboratory is to understand in molecular details the epigenetic functions of nuclear Argonaute proteins and their associated short RNAs in animals. We are using the nematode Caenorhabditis elegans as a model system to test the hypothesis that nuclear Argonaute proteins and their associated short 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:
- The molecular mechanism by which short RNAs regulate transcription and chromatin organization.
- The role of short RNAs in epigenetic inheritance during animal development.
- The function of short RNAs as an adaptive epigenetic system for propagating the memory of stress responses.
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)
- 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)
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.
Personal website: www.cecerelab.com