How sleep deprivation and learning regulate gene expression in the brain
We use genomic approaches to understand gene expression and its epigenetic regulation in response to learning and sleep deprivation. This requires combining behavioral paradigms in mice, molecular biology and the analysis of high-throughput data in the brain in vivo. In her post-doctoral work Dr. Peixoto revealed differences in the gene expression regulation by memory acquisition and retrieval. She also uncovered translation as being specifically regulated by lack of sleep. This work serves as the foundation of several studies in the lab. We continue to collaborate to use genomic approaches to understand fundamental properties of sleep. Applying methodology aimed at ensuring reproducibility of transcriptome studies we have been able to define the gene expression changes that are linked to recovery from sleep loss.
- Memory consolidation and retrieval impact different epigenetic processes that regulate gene expression. BMC Genomics. 2015.
- Genomic analysis of sleep deprivation reveals mTOR-dependent translational inhibition in the hippocampus. Cover Article. Physiol Genomics. 2012.
- Removal of unwanted variation reveals novel patterns of gene expression linked to sleep homeostasis in murine cortex. BMC Genomics. 2016.
How sleep and learning affect transcriptional and epigenetic regulation in Autism Spectrum Disorders
The Peixoto lab uses genomic and candidate gene approaches to study neurodevelopmental disabilities, in particular ASD. We focus on two factors that affect to the greatest extent the quality of life of affected individuals and their families: learning and sleep impairments associated with ASD. Using high-throughput sequencing and software we developed to study how learning affects chromatin accessibility in the mouse hippocampus we showed that learning recapitulates development at the epigenetic level, highlighting regulatory regions in the genome associated with ASD in patients. We have also established the first mouse model with both construct and face validity to study sleep problems in ASD. Currently we are using Shank3 mutant mice to study the mechanism by which sleep, and development interact in ASD, with a focus on epigenetic and transcriptional regulation.
- Learning-dependent chromatin remodeling highlights non-coding regulatory regions linked to Autism. Cover Article. Science Signaling. 2018.
- Highlighted in Science Signaling: New connections: Signaling in Learning Disability.
- Shank3 Modulates Sleep and Expression of Circadian Transcription Factors. Elife. 2019
- Highlighted in Science Translational Medicine: SHANK3 puts Autism to sleep.
Reproducible biology from “omics” data analysis
Another focus of the Peixoto lab is reproducible bioinformatic research, with the goal of producing novel and reliable neuroscience findings from high-throughput sequencing data. One of the main obstacles hindering the ability of genome-wide studies to uncover novel biological processes in the brain is data analysis, specifically the ability to dissociate signal from biological noise. Together with our long-standing collaborator Dr. Davide Risso, we have pioneered the application of reproducible data analysis to the study of gene expression regulation in the brain. We have demonstrated the effects of appropriate data analysis on the biological insight of RNA-seq studies in Neuroscience and developed a tutorial to guide accurate normalization of data. We developed a similar framework for differential epigenomic studies, DEScan, which is now publicly available as an R/Bioconductor package. Currently, we are focusing on accurate and reproducible analysis of differential single-cell and single-nuclear RNA-seq data in the brain in response to stimuli.
Do you want to do research in the Peixoto Lab?
We consider applications from enthusiastic and hard-working students eager to know more about Autism Spectrum Disorders, Sleep and Genomics. To apply, email firstname.lastname@example.org the following: a cover letter stating why you want to join the lab and what you envision your work in the lab will be, an up to date CV, the contact information for 2 references (if not in your CV), the date you will like to start your research and for how long you will like to pursue research. Send your email at least 3 months before your desired start date. Applications that do not comply with the above guidelines will not receive a response.