Four of the labs in MCDB use Drosophila to address fundamental questions in cell and developmental biology. Drosophila provides a remarkable experimental system. The genetics and genomics resources are extraordinary and, especially when combined with biochemical, cell biological and imaging approaches, allow for rapid progress. The fly labs in MCDB collectively make use of the full range of possible technologies. The extensive interactions between the fly labs makes it simple for all labs to take advantage of current and classical approaches. To promote such interactions, there is a weekly meeting at which one researcher - PI, postdoc, or graduate student - presents their work to the entire group.
Research in the Fischer lab is focused on the regulation of Notch signaling pathway by endocytosis and ubiquitin.
Cho B, Fischer JA (2011) Ral GTPase promotes asymmetric Notch activation in response to Frizzled/PCP signaling by repressing ligand-independent receptor activation. Development 138, 1349-1359
Banks SML, Cho B, Eun SH, Lee J-H, Windler SL, Xie X, Bilder D, Fischer JA (2011) The Functions of Auxilin and Rab11 in Drosophila Suggest that the Fundamental Role of Ligand Endocytosis in Notch Signaling Cells is Not Recycling. PLoS ONE 6(3):e18259
Weinmaster G, Fischer JA (2011) Notch ligand ubiquitylation: what is it good for? Developmental Cell 21, 134-144.
Xie X, Fischer JA (2012) Drosophila Epsin’s role in Notch ligand cells requires three Epsin protein functions: the lipid binding function of the ENTH domain, a single Ubiquitin interaction motif, and a subset of the C-terminal protein binding modules. Developmental Biology 363, 399-412
Cho B, Fischer JA (2012) Ral inhibits ligand-independent Notch signaling in Drosophila. Small GTPases 3, 186-191
Lee J-H, Fischer JA (2012) Drosophila Tel2 is expressed as a translational fusion with EpsinR and is a regulator Wingless signaling. PLoS ONE, in press
The Macdonald lab studies the post-transcriptional regulatory mechanisms that underlie axial patterning of the oocyte and specification of the embyronic germline. A key issue is how the oskar mRNA is translated selectively at the posterior pole of the oocyte: how is translation repressed prior to localization, and how is translation activated after localization? In our analysis of translational control we discovered that this form of regulation can be exerted in trans, with the regulatory elements on one molecule of oskar mRNA conferring regulation on other molecules of the mRNA. We suspect that this phenomenon is made possible by the packaging of oskar transcripts into particles, and are exploring this and other models.
Reveal B, Yan N, Snee MJ, Pai C-I, Gim Y, Macdonald, PM (2010) BREs mediate both repression and activation of oskar mRNA translation and act in trans. Developmental Cell 18, 496-502.
Macdonald, PM (2011) mRNA localization: assembly of transport complexes and their incorporation into particles. Current Opinion in Genetics and Development 21, 407-413.
Reveal B, Garcia C, Ellington A, Macdonald PM (2011) Multiple RNA binding domains of Bru confer recognition of diverse binding sites for translational repression. RNA Biology 8, 1047-1060.
In the Papoulas lab research is aimed at understanding two processes that control the formation of the first polarized epithelial cell layer in early Drosophila embryos: Golgi-dependent membrane secretion and Fragile X mental retardation protein-dependent translational regulation. These processes are studied using an integrated experimental approach that combines the advantages of biochemistry, genetics, molecular biology and live embryo imaging.
Papoulas O, Monzo KF, Cantin GT, Ruse C, Yates JR 3rd, Ryu YH, Sisson JC (2010) dFMRP and Caprin, translational regulators of synaptic plasticity, control the cell cycle at the Drosophila mid-blastula transition. Development 137, 4201-9.
Reich J, Papoulas O (2012) Caprin controls follicle stem cell fate in the Drosophila ovary. PLoS One 7(4):e35365.
The Stein lab is interested in understanding how dorsal-ventral polarity is established during oogenesis and embryogenesis. A key step involves the action of the Pipe protein, which mediates oligosaccharide sulfation. An intensive search for a Pipe target was recently successful, and provides the means to ask how the action of Pipe leads to proper patterning.
Zhang Z, Zhu X, Stevens LM, Stein D (2009) Distinct functional specificities are associated with protein isoforms encoded by the Drosophila dorsal-ventral patterning gene pipe. Development 136, 2779-2789.
Zhang Z, Stevens LM, Stein D (2009) Sulfation of eggshell components by Pipe defines dorsal-ventral polarity in the Drosophila embryo. Current Biology 19, 1200-1205.
Cho YS, Stevens LM, Stein D (2010) Pipe-dependent ventral processing of Easter by Snake Is the defining step in Drosophila embryo DV axis formation. Current Biology 20, 1133-1137.
Cho, YS, Stevens LM, Sieverman KJ, Nguyen J, Stein D (2012). A ventrally localized protease in the Drosophila egg controls embryo dorsoventral polarity. Curr. Biol. 22, 1013-1018.