BBS Faculty Member - Angela DePace

Angela DePace

Department of Systems Biology

Harvard Medical School
Warren Alpert Bldg, Room 452A - Systems Biology
200 Longwood Ave
Boston, MA 02115
Tel: 617-432-7410
Fax: 617-432-5012
Email: angela_depace@hms.harvard.edu
Visit my lab page here.



My group is broadly interested in the evolution of transcriptional networks in animals. Whole genome sequence for a wide variety of organisms has shown us that across taxa, the set of protein coding genes is remarkably similar. How is this common genetic toolkit deployed in new configurations to generate organismal diversity? The evolutionary importance of changes in gene regulation during development is now clear, and a handful of examples have successfully traced the path from distinct phenotypes, to changes in gene expression, and finally to specific changes in genomic regulatory sequence. Yet we lack general principles describing how regulatory sequence relates to its output as gene expression patterns in space and time, severely limiting our understanding of how these sequences are functionally constrained during evolution.

Gene expression in metazoans is controlled by the interaction among cis-regulatory elements (sometimes called enhancers), silencers, insulators, chromatin structure and core promoters. The vast majority of gene specific spatial and temporal information is contained in cis-regulatory elements, which are collections of binding sites for sequence specific DNA-binding transcription factors. Our current work is focused on two parallel questions. First, how do collections of transcription factor binding sites integrate information to produce gene expression patterns? And second, how do cis-regulatory elements and their associated expression patterns evolve?

We focus on the early development of multiple Drosophila species, and integrate a wide variety of experimental and computational approaches. The early development of Drosophila melanogaster is directed by an extremely well characterized transcriptional network, giving us a large number of known transcription factors and regulatory elements to work with. Twelve Drosophila species have recently been sequenced, and more genomic resources are on the way. The relatively simple geometry of the early embryo has allowed us to develop quantitative imaging techniques that yield gene expression information for every cell in the entire embryo over time. Together, these resources give us the opportunity to bring a quantitative system-wide approach to evolutionary developmental biology.



Last Update: 6/25/2014



Publications

For a complete listing of publications click here.

 


 

Comparing mRNA levels using in situ hybridization of a target gene and co-stain. Wunderlich Z, Bragdon MD, DePace AH. Methods. 2014 Jun 15;68(1):233-41. doi: 10.1016/j.ymeth.2014.01.003. Epub 2014 Jan 13. PMID: 24434507

Cellular resolution models for even skipped regulation in the entire Drosophila embryo. Ilsley GR, Fisher J, Apweiler R,
Depace AH, Luscombe NM. Elife. 2013 Aug 6;2:e00522. doi: 10.7554/eLife.00522. PMCID:PMC3736529

Genetics. 2013 Jan;193(1):51-61. doi: 10.1534/genetics.112.144915. Epub 2012 Oct 26. Depleting Gene Activities in Early Drosophila Embryos with the "Maternal-Gal4-shRNA" System. Staller MV, Yan D, Randklev S, Bragdon MD, Wunderlich ZB, Tao R, Perkins LA,
Depace AH, Perrimon N.

Mol Syst Biol. 2012;8:604. doi: 10.1038/msb.2012.35. Dissecting sources of quantitative gene expression pattern divergence between Drosophila species. Wunderlich Z, Bragdon MD, Eckenrode KB, Lydiard-Martin T, Pearl-Waserman S,
DePace AH.



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