Dr Dan Bose

Research Overview 
Our lab investigates the hidden regulatory layers of the human genome, specifically focusing on how non-coding RNAs and flexible protein regions coordinate gene expression.

Key Research Areas:

• Enhancer RNAs (eRNAs): While only a small fraction of our genome codes for proteins, much of the rest is transcribed into non-coding RNA. Our research focuses on enhancer RNAs (eRNAs)—functional molecules produced from genetic ""hotspots"" called enhancers. In humans, enhancers are critical for cell-specific gene expression, but they are also primary sites for mutations in diseases like motor neuron disease. We investigate how the unique structures of eRNAs control gene expression and what happens when these processes fail.
• Protein Disorder (IDRs): Most proteins are defined by stable, complex structures, but many contain ""intrinsically disordered regions"" (IDRs)—flexible chains that lack a fixed shape. We study how these IDRs control Creb Binding Protein (CBP), an essential enzyme that controls how DNA is packaged into chromatin. Because CBP is largely composed of IDRs, we are working to understand how these flexible regions shape its function and its interactions with eRNAs.
• Decoding Disease: Since enhancers are hotspots for disease-linked mutations (e.g., in motor neuron disease), we explore how eRNA sequence and structure dictate healthy vs. diseased cell states. While mutations in ""structured"" proteins are often obvious (like a broken gear), mutations in disordered regions are more subtle. We are uncovering how these ""floppy"" chains lead to complex pathologies.

Methodology:
We bridge the gap between ""in vitro"" and ""in vivo"" by combining:

• Structural Biology: Cryo-EM and Biophysics.
• Cellular Imaging: Advanced single-molecule microscopy and Molecular Biology.
• Systems Biology: Functional Genomics.