Novel non-coding RNAs in regulating cancer epigenome

This opportunity will remain open until a suitable candidate has been found and so early applications are encouraged.

Cancer-associated changes in gene expression and genome stability are often attributed to variations in DNA methylation. The incidence/rates of cancers increases in the elderly. Ageing-associated changes in epigenetic modifications like DNA methylation result in increased burden of coexisting diseases and frailty, that impacts treatment choices, tolerance, and outcomes. DNA methylation is maintained by the enzyme DNA methyl-transferase-1 or DNMT1 whose activity is affected in age-dependent manner. Our recent findings (Jones et al, 2021, iScience) show that DNMT1 activity is regulated by non-protein-coding RNAs (ncRNAs). CRISPR-mediated removal of selected ncRNAs display genomic and cellular changes (such as DNA hypomethylation, signs of DNA instability, changes in cell cycle) similar to that observed in ageing cancer cells. To understand ageing-associated changes in DNA methylation and their association with cancer, there is a need study how DNMT1 methylation is regulated by its interaction with ncRNAs.

This project aims to understand the interplay of ncRNAs and DNA methylation in cancer.

The supervisory team has expertise in RNA biology, transcriptomics, epigenetics and computational biology. The recruited PhD student will use modern techniques such as transcriptomics and CRISPR-Cas9 mediated genome engineering alongside molecular and cell biology approaches to investigate the molecular mechanisms underlying ncRNA mediated regulation of DNA methylation. The study will utilise cancer cell line models and primary patient samples. This is a unique opportunity to work in a multi-disciplinary environment in two world-leading universities in the UK. In addition to scientific training, there is ample opportunity to acquire communication and presentation skills at scientific meetings and many opportunities for publications. Such experience should help establish a scientific career in academia or industry.

We, as a part of Institute of systems, molecular and integrative biology (ISMIB) and Centre for Drug Safety Science, aim to understand how non-coding RNAs, in response to diseases and drugs, regulate gene expression chromatin landscape through their interactions with the epigenetic machinery (Genome Res, 2021; Trends in Genetics, 2021, EMBO 2019; Nature Comm 2012; Mol Cell 2010).

This is a unique opportunity to work in a multi-disciplinary environment in a world-leading university in the UK. In addition to scientific training, there is ample opportunity to develop communication and presentation skills by participating in many scientific meetings, collaborations, and publications. In short, this project will prepare you in skills needed for a competitive career in academia as well as industry.

We will use our expertise in next-generation sequencing methods, systems biology and bioinformatics to address these aims. The candidate will be benefitted by gaining experience in number of leading topics.

The project has direct relevance to ageing and disease theme. We will use our expertise in next-generation sequencing methods, systems biology and bioinformatics to address these aims. The candidate will be benefitted by gaining experience in number of leading topics.

For any enquiries or to express your interest in applying, please contact: Dr. Aditi Kanhere on: a.kanhere@liverpool.ac.uk