Chromatin regulation plays a key role in nearly all nuclear biological processes such as DNA replication, repair and transcription. Our recent findings have shown that HOT (high-occupancy target) regions are bound by a surprisingly large number of transcription factors. These HOT regions display high levels of chromatin accessibility and CpG-rich sequences in both human and C. elegans (Chen et al, Genome Research 2014). The high accessibility of DNA may be caused by a specific DNA structure that disfavours the occupancy of nucleosomes. Also, these highly accessible DNAs may be susceptible to DNA damage leading to the formation of genetic variants. This idea is supported by a recent report showing that genetic risk variants are enriched in HOT regions in both disease-relevant and cancer cells. The goal of the PhD project is to investigate how epigenetic control contributes to the genome stability and related biological events.
C. elegans is an excellent multicellular model to study the genetic regulatory circuits and molecular mechanisms that underlie human diseases. The high levels of protein conservation and the ease of molecular experiments make C. elegans a powerful model system to identify and characterise novel biological pathways that contribute to the onset of human diseases including cancer. The advertised PhD project will be based on the outcome of our recent genetic screen. We have identified novel genetic interactions between chromatin modifiers that control active promoter chromatin signatures. We will "translate" our novel findings in C. elegans into human leukaemia cells to test the role of the putative conserved regulatory network in human cancer cells. It will apply functional genetic and genomic assays plus molecular and biochemical approaches. The candidate will be closely co-supervised by Dr. Edwin Chen, an expert in oncogenic signalling pathways in leukaemia.
Applicants with a strong interest in genetics/molecular biology/cancer biology are encouraged to apply; especially those with previous research experience in genetic screens in either C. elegans or tissue cultured cells. If you wish to informally enquire regarding more information about the project, please contact Dr. Ron Chen, email: [email protected]
Lab website for Dr. Ron Chen: http://www.ronchenlab.info
Lab website for Dr. Edwin Chen: http://www.edwinchenlab.com/
The studentship is funded by University of Leeds and only for UK and EU applicants.
We are also interested in supporting outstanding non-EU international applicants to apply for internal and external funding.
Leeds Centrally Funded Research Postgraduate Scholarships
Leeds China Scholarships