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  Transcriptome homeostasis in cellular ageing and cancer


   Institute of Dentistry

   Applications accepted all year round  Self-Funded PhD Students Only

About the Project

Project Summary

We have previously established the oncogenic mechanisms of the transcription factor FOXM1 in perturbation of genome stability (1, 2), epigenome (3, 4) and adult progenitor epithelial stem cell proliferation (5). Pan-cancer multi-omics studies have shown that FOXM1 gene amplification lead to mRNA and protein upregulation of FOXM1 in almost all human cancer types (6, 7). Interestingly, FOXM1 upregulation has been shown to delay cellular senescence and extend lifespan (8, 9). Increased speed of transcription elongation, deregulation of RNA splicing and accumulation of circular RNA have been associated with health-span and ageing in several different invertebrate and vertebrate species (10). We hypothesized that FOXM1 is a pivotal gene that regulates transcriptome homeostasis – deregulation of this mechanism leads to ageing and cancer. This project aims to investigate the mechanisms of FOXM1 in ageing and cancer.

Training Facilities & Environment

The project will involve interdisciplinary approaches involving cell and molecular techniques for mechanistic studies, transcriptome profiling, gene expression analysis, drug-library screening for drug discovery, bioinformatics meta-analysis of transcriptome data, exploration of using mathematical model and artificial intelligence (AI) for pattern recognition and biomarker & drug discovery. This project will benefit from the state-of-the-art facilities of the Blizard Institute which support cutting-edge multi-disciplinary research (https://www.qmul.ac.uk/blizard/).

In addition, resources and help with developing AI models could be obtained from QMUL’s newly created Digital Environment Research Institute (DERI) (https://www.qmul.ac.uk/deri/) for digital data science and AI research with links to the Alan Turing Institute, the University Enterprise Zone and East London’s Tech City, a vibrant cluster of high-tech companies.

Admission Requirements

A graduate with at least an equivalent of an upper second-class BSc degree or a merit/distinction in an experimental life science MSc degree is required for this PhD project. The candidate should have strong interests and preferably with some experience in cellular and molecular biology, have some basic concept or interests in bioinformatics, coding or AI machine learning and RNA biology. The candidate should have excellent manual dexterity for careful liquid handling and meticulous in experimental details and data recording essential for long-term longitudinal ageing studies.

If English is not your first language, the standard requirement for English is an IELTS score of 6.5 overall for non-clinical projects and 7 overall for clinical projects (or equivalent). More details about language requirements can be found here.

For more information on the project, please contact Dr Muy Tek Teh.  

For information on the application process, please contact


Biological Sciences (4) Medicine (26)

Funding Notes

We will consider applications from prospective students with a source of funding to cover tuition fees and bench fees for three years full-time or 6 years part-time. Both self-funded and sponsored students will be considered.
UK nationals, Irish citizens and those with settled status under the EU Settlement Scheme or indefinite leave to remain in the UK might be eligible for a doctoral loan for both the cost of tuition fees and a yearly stipend over the course of the PhD programme from Student Finance England: View Website

References

1. Teh, M.T. et al., Upregulation of FOXM1 induces genomic instability in human epidermal keratinocytes. Mol Cancer 9, 45 (2010).
2. Gemenetzidis, E. et al., FOXM1 upregulation is an early event in human squamous cell carcinoma and it is enhanced by nicotine during malignant transformation. PLoS One 4, e4849 (2009).
3. Teh, M.T. et al., FOXM1 induces a global methylation signature that mimics the cancer epigenome in head and neck squamous cell carcinoma. PLoS One 7, e34329 (2012).
4. Hwang, S. et al., Identification of FOXM1-induced epigenetic markers for head and neck squamous cell carcinomas. Cancer 119, 4249-4258 (2013).
5. Gemenetzidis, E. et al., Induction of human epithelial stem/progenitor expansion by FOXM1. Cancer research 70, 9515-9526 (2010).
6. Barger, C.J. et al., Pan-Cancer Analyses Reveal Genomic Features of FOXM1 Overexpression in Cancer. Cancers (Basel) 11, (2019).
7. Hoadley, K.A. et al., Cell-of-Origin Patterns Dominate the Molecular Classification of 10,000 Tumors from 33 Types of Cancer. Cell 173, 291-304 e296 (2018).
8. Ribeiro, R. et al., In vivo cyclic induction of the FOXM1 transcription factor delays natural and progeroid aging phenotypes and extends healthspan. Nat Aging 2, 397-411 (2022).
9. Ouchi, Y. et al., FOXM1 delays senescence and extends lifespan. Nat Aging 2, 373-374 (2022).
10. Debes, C. et al., Ageing-associated changes in transcriptional elongation influence longevity. Nature 616, 814-821 (2023)

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