Understanding the organization of regulatory information in the genome
The Wunderlich lab is interested in studying how regulatory information — when, where, and to what level genes are expressed — is encoded in animal genomes, with the ultimate goal of being able to understand how changes in the sequence of regulatory DNA, e.g. promoters and enhancers, will affect phenotype. Proper gene expression is necessary for the development of an organism from embryo to adult, and mis-regulation of gene expression is implicated in many diseases. As a model system, the lab uses different species and strains of Drosophila and studies transcription regulation of early embryogenesis. The lab uses cellular resolution imaging of gene expression, computational modeling, and genetic manipulations to understand how different sequences of regulatory DNA lead to different functions. This work has uncovered compensatory evolution between multiple pieces of regulatory DNA controlling single genes to maintain proper gene expression patterns and suggests that understanding the mechanism by which many pieces of regulatory DNA . The lab is also developing new model systems to explore how sequence variation between individuals and species affects gene expression.
- Samee MAH, Lydiard-Martin T, Biette KM, Vincent BJ, Bragdon MD, Eckenrode KB, Wunderlich Z, Estrada J, Sinha S, DePace AH. Quantitative Measurement and Thermodynamic Modeling of Fused Enhancers Support a Two-Tiered Mechanism for Interpreting Regulatory DNA. Cell Rep. (2017).
- L Li, Z Wunderlich. An Enhancer’s Length and Composition Are Shaped by Its Regulatory Task. Frontiers in Genetics. (2017).
- Estrada J, Ruiz-Herrero T, Scholes C, Wunderlich Z, DePace AH. SiteOut: An Online Tool to Design Binding Site-Free DNA Sequences. PLoS One. (2016).
- Z Wunderlich, MDJ Bragdon, Ben J Vincent, Jonathan A White, Javier Estrada, AH DePace. Kruppel expression is conserved through compensatory evolution of shadow enhancers. Cell Reports. (2015).
- BJ Vincent*, C Scholes*, MV Staller*, Z Wunderlich*, J Estrada*, J Park*, MD Bragdon*, F Lopez Rivera*, KM Biette*, AH DePace*. Yearly Planning Meetings: Individualized Development Plans Aren’t Just More Paperwork. Molecular Cell. (2015).
*Authors contributed equally to this work.
- MV Staller, Meghan DJ Bragdon, Z Wunderlich, J Estrada, AH DePace. A gene expression atlas of a bicoid-depleted Drosophila embryo reveals early canalization of cell fate. Development. (2015).
- MV Staller, BJ Vincent, Meghan DJ Bragdon, Z Wunderlich, J Estrada, AH DePace. Shadow enhancers enable Hunchback bifunctionality in the Drosophila embryo. PNAS. (2015).
- Z Wunderlich, MD Bragdon, and AH DePace. Comparing mRNA levels using in situ hybridization of a target gene and co-stain. Elsevier Methods. (2014).
- Z Wunderlich, MD Bragdon, K Eckenrode, T Martin, S Pearl, and AH DePace. Dissecting sources of quantitative gene expression pattern divergence between Drosophila species. Molecular Systems Biology. (2012).
- MV Staller, D Yan, S Randklev, MD Bragdon, Z Wunderlich, R Tao, LA Perkins, AH DePace, N Perrimon. Depleting gene Activities in Early Drosophila Embryos with the “maternal-Gal4 – shRNA” system. Genetics. (2012).
- Z Wunderlich, AH DePace. Modeling transcriptional networks in Drosophila development at multiple scales. Current Opinion in Genetics and Development. (2011).
- CC Fowlkes*, K Eckenrode*, MD Bragdon*, M Meyer, Z Wunderlich, L Simirenko, CL Luengo Hendriks, SVE Keränen, C Henriquez, DW Knowles, MD Biggin, MB Eisen, AH DePace. A conserved developmental patterning network produces quantitatively different output in multiple species of Drosophila. PLoS Genetics. (2011).