Associate Professor of Systems Biology
Harvard Medical School, Department of Systems Biology
Alpert Building, Room 513
200 Longwood Ave.
Boston, MA 02115
Lab Size: Between 5 and 10
Our long-term goal is to understand how regulatory DNA dictates transcriptional network behavior and, ultimately, organismal phenotype and evolution. Our approach is mechanistically motivated: we believe that understanding the molecular mechanisms that drive transcription will lead to models of gene regulation that can predict the functional consequences of regulatory sequence changes and guide production of new types of regulatory circuits.
The strength of our system lies in the breadth and depth of experimental, computational and theoretical approaches that are possible in Drosophila embryos. The nuclei in blastoderm embryos are in a monolayer at the surface, making it easy to image transcription quantitatively in both fixed and live tissue. All the players in the patterning network are known making it ideal for systems-level studies. We can also perturb the network using genetics, transgenesis and genome engineering. Finally, the availability of many genome sequences from related species and natural populations makes insects an outstanding clade for evolutionary studies. Combined, these tools allow us to go “soup to nuts” — from genotype to phenotype — at a level of detail that is impossible in other animal systems. The lessons we learn will be widely applicable to other animal systems including humans, as has historically been the case for research on Drosophila transcription.
Wunderlich Z, Bragdon, MD, Vincent, BJ, White, JA & DePace, A.(2016). Krüppel Expression Levels Are Maintained through Compensatory Evolution of Shadow Enhancers.Cell Rep.14(12), PMID: 27028762 PMCID: PMC Journal - In Process
Estrada, J, Ruiz-Herrero, T, Scholes, C, Wunderlich, Z & DePace, A. (2016). SiteOut: An Online Tool to Design Binding Site-Free DNA Sequences.. PLoS ONE. 11(3), PMID: 26987123 PMCID: PMC4795680
Vincent, BJ, Estrada, J & DePace, A. (2016). The appeasement of Doug: a synthetic approach to enhancer biology.Integrative Biology. PMID: 26936291
Wunderlich, Z, Bragdon, MD, Vincent, BJ, White, JA, Estrada, J & DePace, AH. (2015). Krüppel Expression Levels Are Maintained through Compensatory Evolution of Shadow Enhancers. Cell. 12(11), 1740-7 PMID: 26344774 PMCID: PMC4581983
Vincent, BJ, Scholes, C, Staller, MV, Wunderlich, Z, Estrada, J, Park, J, Bragdon, MD, Lopez, Rivera F, Biette, KM, Biette, KM & DePace, AH. (2015). Yearly planning meetings: individualized development plans aren't just more paperwork. Mol Cell. 58(5), 718-21 PMID: 26046646
Staller, M.V., Fowlkes, C.C., Bragdon, M.D., Wunderlich, Z., Estrada, J. & DePace, A.H. (2015). A gene expression atlas of a bicoid-depleted Drosophila embryo reveals early canalization of cell fate. Development. 142(3), 587-596 PMCID: PMC4302997
Staller, M.V., Vincent, B.J., Bragdon, M.D., Lydiard-Martin, T., Wunderlich, Z., Estrada, J. & DePace, A.H. (2015). Shadow enhancers enable Hunchback bifunctionality in the Drosophila embryo. Proc Natl Acad Sci U S A. 112(3), 785-790 PMCID: PMC4311800
Wunderlich, Z., Bragdon, M.D. & DePace, A.H.(2014). Comparing mRNA levels using in situ hybridization of a target gene and co-stain. Methods. 68(1), 233-241 PMID: 24434507 PMCID: PMC4048779
Ilsley GR, Fisher J, Apweiler R, Depace AH, Luscombe NM. (2013). Cellular resolution models for even skipped regulation in the entire Drosophila embryo. Elife. PMID: 23930223
Staller MV, Yan D, Randklev S, Bragdon MD, Wunderlich ZB, Tao R, Perkins LA, Depace AH, Perrimon N. (2013). Depleting gene activities in early Drosophila embryos with the "maternal-Gal4-shRNA" system. Genetics. 51-61 PMID: 23105012 PMCID: PMC3527254
Wunderlich Z, Bragdon MD, Eckenrode KB, Lydiard-Martin T, Pearl-Waserman S, DePace AH. (2012). Dissecting sources of quantitative gene expression pattern divergence between Drosophila species. Mol Syst Biol. 604 PMID: 22893002 PMCID: PMC3435502
Wunderlich, Z. & DePace, A.H. (2011). Modeling transcriptional networks in Drosophila development at multiple scales. Curr Opin Genet Dev. 21(6), 711-8 PMID: 21889888
Meyer M, Munzner T, DePace A & Pfister H. (2011). MulteeSum: A Tool for Comparative Spatial and Temporal Gene Expression Data. IEEE Trans Vis Comput Graph. 16(6), 908-17
Fowlkes, C.C., Eckenrode, K.B., Bragdon, M.D., Meyer, M., Wunderlich, Z., Simirenko, L., Luengo Hendriks, C.L., Keränen, S.V., Henriquez, C., Knowles, D.W., Biggin, M.D., Eisen, M.B. & DePace, A.H. (2011). A conserved developmental patterning network produces quantitatively different output in multiple species of Drosophila. PLoS Genet. 7(10), PMID: PMCID: PMC3203197