/ Paola Bellosta, Ph.D.
Associate Professor
Dept. of Biology
Convent Avenue at 138th Street
New York, NY 10031
A research fellowship is available for a graduate student
Drosophila Genetics Unit, Evolutionary and Experimental Biology Department of the University of Bologna.
The candidate will spend the full two-years period at the CUNY - City University of New York - in my laboratory working on:
Studies on transcriptional regulation by the Myc proto-oncogene using Drosophila as a model system
myc is a gene whose deregulation is prominent in cancer, and it is a critical regulator of growth in flies and mammals. Genetic studies in vertebrates and invertebrates suggest that signals from the conserved patterns organizing morphogens such as Insulin, BMP/Dpp/TGF-b Wnt/Wingless, and Hedgehog contribute to this program, but it is unclear how they monitor and regulate growth. In our laboratory we are trying to answer these questions using two different approaches. First, using a biochemical approach we were able to demonstrate that Myc protein stability is regulated by its phosphorylation with a specific code by the GSK3 and CK1 kinases (ms. in preparation). Second, our and others microarray analysis reveal that the majority of Myc target genes play a role in ribosome biogenesis, protein synthesis and metabolism, consistent with dMyc’s role in cellular growth. We recently demonstrated in vitro using S2 cells, that stimulation of cells with Insulin increases Myc protein level and this event depends on members of Tor signaling. Our data are consistent with a role of dMyc on Insulin and Nutrients signaling and with dMyc’s role in cellular growth (3 and ms. in preparation). At the molecular level, Myc forms a complex with Max, another helix-loop-helix. Myc:Max complex binds DNA and activates the transcription of nearby genes. Several biochemical approaches to identify possible Myc adaptors/interactors led to the isolation of specific components of the chromatin remodeling complex, such as TRRAP, Tip48 and Tip49. We have been able to demonstrate that the two co-factors Tip48/Reptin and Tip49/Pontin play an essential role in proliferation of Drosophila S2 cells, and pontin and reptin show a strong dominant genetic interaction with dmyc in vivo (1). We are currently performing a genetic screen in order to identify new components for Myc transcriptional activity.
Current on-going Research:
- characterization of the signaling which modulates Myc protein in response to Insulin and Tor signaling
- analysis of dMyc targets using a Genetic Screen
Selected Publications:
1-Bellosta P., Hulf T., Usseglio F., Aragnol D. and Gallant P.
Myc interacts genetically with Tip48 and Tip49 to control growth and proliferation during Drosophila development Proc. Nat. Acad. Sci. USA 2005 102: 11799-804
2-Hulf T., Bellosta P., Svensson D., Barbour A. and Gallant P.
Whole-genome analysis reveals a strong positional bias of conserved dMyc.dependent E-boxes Mol. Cell. Biol. 2005. 25: 3401-10
3-De la Cova C., Abril, M. Bellosta P., Gallant P. and Johnston L,
Drosophila myc regulate organ size by inducing cell competition.Cell 2004 117: 107-116