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Department of Physiology, Development and Neuroscience

 

Research

Our main focus is the investigation of the regulatory architecture of the genome through developing and exploiting genomic technologies in Drosophila. In particular we are using Chromatin immunopurification coupled with either genomic microarray or high throughput-sequencing for large-scale analysis of the target sites of transcription factors and other DNA-binding and chromatin-associated proteins in the Drosophila genome. In collaboration with Steve Russell’s lab in the Dept of Genetics/Cambridge Systems Biology Centre, we have carried out analyses of the genomic targets of insulators and silencers and the Hox transcription factors. This has provided insight into the roles of insulators and silencers and, for example, we have shown that the insulator protein CTCF bounds defined regulatory domains in the Bithorax complex. Our studies on Hox protein binding have emphasised the role of chromatin accessibility in Hox target selection.

Hox protein target specificity

The Hox proteins provide a model for how transcription factors identify their target sites in the genome. We are investigating the basis of Hox specificity including the role of Hox-cofactors such as Extradenticle and the role of chromatin state in target selection.

Regulatory architecture of the genome

We are investigating of the regulatory architecture of the genome through the genomic mapping of the binding sites of chromatin-associated proteins, especially proteins associated with insulator function and the analysis of the connection between chromosomal architecture and transcriptional regulation.

Chromatin state and cell differentiation

We are investigating the mechanisms of transcriptional regulation using the powerful model of Drosophila spermatogenesis where spermatocyte differentiation involves a major developmental switch with the activation of the spermatocyte transcriptional program involving several thousand genes. We are particularly interested in the role of chromatin-based mechanisms in this process.

Nuclear organisation

We are also interested in the links between chromatin organisation in the nucleus and the regulation of gene expression and we are investigating the nuclear organisation of gene expression in the large and highly organised nucleus of the Drosophila primary spermatocyte.

Collaborators

Damiano Porcelli (Post-doc)
Sherif El-Sharnouby (Post-doc)
Bettina Fischer (Research Assistant/Bio-informatician)
Alex Chen (PhD student, Dept of Genetics)
Steve Russell (PI, Dept of Genetics)

Publications

Key publications: 

Adryan B, Woerfel G, Birch-Machin I, Gao S, Quick M, Meadows L, Russell S, White R, (2007), Genomic mapping of Suppressor of Hairy-wing binding sites in Drosophila, Genome Biol, 8:R167

Holohan EE, Kwong C, Adryan B, Bartkuhn M, Herold M, Renkawitz R, Russell S, White R, (2007), CTCF Genomic Binding Sites in Drosophila and the Organisation of the Bithorax Complex, PLoS Genet, 3:e112

Kwong C, Adryan B, Bell I, Meadows L, Russell S, Manak JR, White R, (2008), Stability and dynamics of Polycomb target sites in Drosophila development, PLoS Genet, 4:e1000178

Choo SW, White R, S Russell, (2011), Genome-wide analysis of the binding of the Hox protein Ultrabithorax and the Hox cofactor Homothorax in Drosophila, PLoS ONE, 6: e14778

Redhouse JL, Mozziconacci J, White R, (2011), Co-transcriptional architecture in a Y loop in Drosophila melanogaster, Chromosoma, 12: 0399-407

El-Sharnouby S, Redhouse J, White RAH, (2013), Genome-wide and cell-specific epigenetic analysis challenges the role of Polycomb in Drosophila spermatogenesis, PLoS Genet, 9: e1003842

Magbanua, JP, Runneburger E, Russell S, White R, (2015), A variably occupied CTCF binding site in the Ultrabithorax gene in the Drosophila bithorax complex, Mol. Cell. Biol. 35, 318–330

 

Teaching and Supervisions

Teaching: 

MVST 1A Histology

Part 2 PDN Module P4 “Development: Patterning the Embryo”, Module P7 “Genes and Physiology”, Module P9 “Cell assembly and interactions”

Picture of  Rob  White

Contact Details

+44 (0) 1223 768080, Fax: +44 (0) 1223 333840
Email address: