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The role of epigenetic mechanisms in the control of post-stress recovery of cancer cells


Project Description

Project details:

In recent years, it has become apparent that epigenetic mechanisms play an important role in the cellular response to stress; however, exact mechanisms involved are still poorly understood despite continued efforts.

We recently discovered a novel role of the histone demethylase KDM4A in the regulation of protein biosynthetic capacity which is affected by the majority of cellular stresses. The preliminary analysis of genome-wide distribution of KDMA4 in stressed and recovering cells demonstrated dynamic association of KDM4A with the promoters of significant number of genes and we hypothesise that KDM4A is the master-regulator that controls the stress-related changes in the activity of a number of genes, some of which are specific for the stress type (i.e. heat-shock proteins), while others are common to all types of stress (i.e. rRNA).

Our preliminary analysis of KDM4A interactome in stressed and recovering cells suggests the existence of a number of distinct KDM4A complexes with yet unknown functions. We hypothesise that various signalling pathways (either activated by stress or during the post-stress recovery) are changing the KDM4A phosphorylation profile, affecting its interactome, and this is a generic mechanism of stress-dependent, KDM4A-driven regulation of chromatin structure.

The primary goal of this project is to verify these hypotheses and deepen our knowledge of the fundamental processes regulating cell life and death. Our results will have an impact on the understanding of the fundamental aspects of cell adaptation to the significant changes in the extracellular environment, as well as the understanding of diseases associated with abnormal growth and proliferation (e.g. cancer, cardiac hypertrophy) and the development of replacement cell therapy.

This project is a part of ongoing collaboration with Australian National University, Canberra.

This project will be supervised by Dr Konstantin Panov (Queen’s University School of Biological Sciences), Dr Simon McDade (Queen’s University School of Medicine, Dentistry and Biomedical Sciences), and Dr Bobby Graham (Queen’s University School of Biological Sciences).

All applicants must meet the academic entry requirements: https://www.qub.ac.uk/courses/postgraduate-research/biological-sciences-phd.html#entry

Funding Notes

Only UK and EU students are eligible to apply. Before applying, it is strongly recommended that you read the full information on eligibility criteria available from DfE: View Website.

Please note in particular that not all successful applicants may be eligible to receive a full studentship (i.e. fees and stipend) - please read in detail the Residency and Citizenship requirements in the document linked to above.

How good is research at Queen’s University Belfast in Public Health, Health Services and Primary Care?

FTE Category A staff submitted: 29.60

Research output data provided by the Research Excellence Framework (REF)

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