How combinations of DNA 'switches' control gene activity
Analysis of combinatorial cis-regulation in synthetic and genomic promoters
This project looks at how combinations of DNA regulatory elements turn genes on or off in different cell types to help explain how non-coding genetic changes can cause disease.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Washington University NIH-funded |
| Lab location | 1 site (Saint Louis, United States) |
| Project ID | NIH-11176889 on NIH RePORTER |
What this research studies
Researchers will measure the activity of many candidate regulatory DNA sequences across individual cells inside intact mammalian tissues using a single-cell massively parallel reporter assay (scMPRA). They will compare synthetic and natural genomic promoter sequences to see how number, spacing, orientation, and strength of transcription factor binding sites change activity in specific cell types. The team will fit a formal thermodynamic model that represents each protein–DNA and protein–protein interaction by its free energy (ΔG) to quantify independent and interacting contributions. These measurements and models aim to build a predictive ‘regulatory grammar’ that links non-coding DNA variation to cell-type-specific gene control.
Who could benefit from this research
Good fit: Ideal candidates for any direct participation would be people willing to provide tissue samples or who have inherited conditions suspected to involve non-coding genetic variants, typically through collaboration with the research center.
Not a fit: Patients whose conditions are caused entirely by non-genetic factors or whose care does not depend on understanding gene regulatory variation are unlikely to gain direct benefit from this specific project.
Why it matters
Potential benefit: If successful, this work could help doctors and researchers interpret genetic test results by pinpointing which non-coding DNA changes affect gene regulation and disease risk.
How similar studies have performed: Massively parallel reporter assays have previously generated useful data on regulatory elements, but combining single-cell in vivo MPRA across tissues with formal thermodynamic modeling is a novel and less-tested approach.
Where this research is happening
Saint Louis, United States
- Washington University — Saint Louis, United States (Active)
Researchers
- Principal investigator: Cohen, Barak a — Washington University
- Study coordinator: Cohen, Barak a
About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page below.