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Epigenetic control in cell fate specification and human diseases

  • Full or part time
  • Application Deadline
    Applications accepted all year round
  • Self-Funded PhD Students Only
    Self-Funded PhD Students Only

Project Description

Our main research interest is to understand the mechanistic action of epigenetic control in common human diseases. We aim to identify and characterise the conserved regulatory circuits underlie human diseases such as cancer, and age-related diseases. Therefore, we use the powerful genetic model organism C. elegans to study conserved regulatory events at the chromatin level. These round worms (nematodes) share 70% of proteins encoded in the human genome. Most proteins involved in transcription and chromatin function are highly conserved. The comprehensive genetic tools (e.g. the genome-wide RNAi library), short life cycle (only 3 days), and the ease of molecular experiments (e.g. CRISPR genome editing) make C. elegans a great experimental system to address big biological questions to aid the understanding of the underlying mechanisms for human diseases.    

CpG-rich promoters are frequently present across the C. elegans and human genome. These widely active genomic regions have been found to harbour highly occupied target (HOT) regions for transcription factors (Chen et al., 2014 Genome Research). It suggests that CpG island promoters can function as regulatory hubs for chromatin regulators and consequently may modulate transcriptional activities. CFP-1 is an evolutionarily conserved non-methylated CpG binding protein that binds to CpG-rich promoters in humans and C. elegans. This conserved epigenetic regulator is part of the COMPASS complex that contains the major transferase for histone 3 lysine 4 tri-methylation (H3K4me3); SET-2 in C. elegans and Set1 in humans. H3K4me3 is frequently found in active promote regions, thus it has been used as an active promoter mark. The role of H3K4me3 in gene expression is unclear. To address this key question in epigenetic control, we are characterising cfp-1 and set-2 loss-of-function C. elegans mutants for their ability in inducing gene expression, specifying cell fate, and modulating chromatin architectures. In parallel, we are also "translating" our C. elegans findings into human cancer biology using cancer cell-based studies.

Applicants with a strong interest in gene & development and cancer biology are encouraged to apply.

Our lab website: http://www.ronchenlab.info

References

Chen RAJ, Stempor P, Down TA, Zeiser E, Feuer SK, Ahringer J Extreme HOT regions are CpG-dense promoters in C. elegans and humans Genome Research 24 1138-1146, 2014
DOI:10.1101/gr.161992.113

Chen RAJ, Down TA, Stempor P, Chen QB, Egelhofer TA, Hillier LDW, Jeffers TE, Ahringer J The landscape of RNA polymerase II transcription initiation in C. elegans reveals promoter and enhancer architectures. Genome Research 23 1339-1347, 2013
DOI:10.1101/gr.153668.112




How good is research at University of Leeds in Biological Sciences?

FTE Category A staff submitted: 60.90

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