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Epigenetics and chromatin regulatory proteins in Drosophila

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  • Full or part time
    Prof Mattias Mannervik
  • Application Deadline
    No more applications being accepted
  • Funded PhD Project (Students Worldwide)
    Funded PhD Project (Students Worldwide)

About This PhD Project

Project Description

Epigenetics can be defined as non-genetic changes in cellular phenotype that are transmitted through cell-divisions. Epigenetic patterns of histone modifications contribute to the maintenance of cell- and tissue-specific gene expression. They are therefore important for maintenance of specific cell identities and have been implicated in human disease, most prominently in cancer.

In this project, genetic and genomic analyses of chromatin and its regulators will be performed in Drosophila melanogaster to study transcription and formation of epigenetic chromatin states. The histone complement of Drosophila will be replaced with mutant histones to study the impact of individual histone residues on gene expression in a multi-cellular organism. The functions of the CBP co-activator in transcription and at Polycomb-repressed chromatin will be explored with a specific inhibitor. These studies of chromatin and its regulators by the outstanding repertoire of experimental manipulations available in Drosophila should provide important insights into cell differentiation, proliferation and the mechanisms of carcinogenesis. The project involves molecular, genetic and genomic approaches and experience with molecular cloning, Chromatin immunoprecipitation (ChIP), high-throughput sequencing, and fly genetics is desirable.

References

A cis-regulatory map of the Drosophila genome.
Nègre N et al.
Nature. 2011 Mar 24;471(7339):527-31. doi: 10.1038/nature09990.

Preferential genome targeting of the CBP co-activator by Rel and Smad proteins in early Drosophila melanogaster embryos.
Holmqvist PH, Boija A, Philip P, Crona F, Stenberg P, Mannervik M.
PLoS Genet. 2012;8(6):e1002769. doi: 10.1371/journal.pgen.

A time of change: Dynamics of chromatin and transcriptional regulation during nuclear programming in early Drosophila development.
Boija A, Mannervik M.
Mol Reprod Dev. 2015 Oct;82(10):735-46. doi: 10.1002/mrd.22517

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