Systems Biology of Development and Gene Regulation
Where Biology, Physics, Engineering, and Informatics meet
Principal Investigator: Ezzat El-Sherif
How Enhancers work during Development
We are interested in understanding how genes are regulated to allow embryonic development. Specifically, we study key genetic elements in mediating gene regulation: Enhancers. An Enhancer is piece of DNA that tells when and where in the embryo a gene turns on or off. Through enhancers, genes are wired into gene regulatory networks that orchestrate embryonic development. Understanding how Enhancers work is an important and challenging problem, and our lab is set to contribute in solving it.
We use two model organisms to study How Enhancers Work during Development: the fruit fly Drosophila melanogaster, and the flour beetle Tribolium castaneum. We specifically study how genes are regulated in the early embryos of these two species.
The fruit fly
The flour beetle
The gene even-skipped is visualized (green) in the early Drosophila embryo
The gene odd-skipped is visualized (magenta) in the early Tribolium embryo
Research Direction 1
How do enhancers regulate wavelike gene expression patterns?
Careful examination of how genes are expressed during the development of many tissue in several species revealed that genes are oftentimes expressed in waves (either periodic to produce periodic patterns, or non-periodic to produce non-periodic patterns). In Research Direction 1, we set to understand how enhancers mediate these wavelike gene expression patterns.
Research Direction 2
What is the role of enhancer RNAs (eRNAs) in Transcription?
Enhancers (like promoters) are often transcribed, producing short RNAs, called enhancer RNAs (eRNAs). It is currently unclear how and why these eRNAs are produced. Our lab is set to solve this mystery by using alternative methodology and model system to those traditionally used to study eRNAs.
Assaying nascent eRNA transcription has been traditionally done in bulk (in cell lines or whole embryos) using genomic techniques like GRO-seq and GRO-cap. Such approaches average eRNA signals over many cells at different cellular states, blurring the dynamics of transcriptional events (e.g. transcription bursting). To study eRNA at the single-cell level, we used single-molecule fluorescent in situ hybridization (smFISH) to visualize nascent eRNA production in the early Drosophila embryos.