Investigating the link between epithelial cell-cell adhesion in chromatin organisation
- Supervisors: Dr Natalia Bulgakova
- Funding: QMUL Principal's Studentship
- Deadline: 31st January 2024
- Expected Start Date: Sept 2024
Research environment
The School of Biological and Behavioural Sciences at Queen Mary is one of the UK’s elite research centres, according to the 2021 Research Excellence Framework (REF). We offer a multi-disciplinary research environment and have approximately 180 PhD students working on projects in the biological and psychological sciences. Our students have access to a variety of research facilities supported by experienced staff, as well as a range of student support services.
In the Bulgakova lab, we study functions and regulation of cell-cell adhesion in epithelial cells. The cell-cell adhesion connects neighbouring cells and is required for tissue integrity. There is growing evidence that cell-cell adhesion also contributes to communication and modulates cell proliferation, differentiation and apoptosis. Not surprisingly, the correct cell-cell adhesion is essential from the early stages of development and its defects are closely linked to diseases such as cancers. In a multidisciplinary approach, we combine genetics, state-of-the-art imaging, omics techniques and bioinformatics to investigate the fundamental principles of cell-cell adhesion biology.
Training and development
Our PhD students become part of Queen Mary’s Doctoral College which provides training and development opportunities, advice on funding, and financial support for research. Our students also have access to a Researcher Development Programme designed to help recognise and develop key skills and attributes needed to effectively manage research, and to prepare and plan for the next stages of their career.
Project description
The epithelium is one of the four basic tissues in multicellular organisms. Cells in all epithelia share fundamental defining characteristics such as apical-basal polarity and intercellular adhesion, mediated by the transmembrane protein E-cadherin. These epithelial cell characteristics and their context-specific behaviour are essential for the correct formation and function of the tissue. Ultimately, these characteristics are defined by the transcriptional profile of the genes expressed by the epithelial cells themselves.
The tissue-specific packaging of DNA into chromatin – a dynamic complex of DNA, RNA and associated proteins – is a decisive contributor to the cell's transcriptional profile. Consequently, altered chromatin organisation and maintenance are linked to multiple developmental diseases and cancers. Our lab has discovered that cell-cell adhesion mediated by E-cadherin controls chromatin organisation in epithelial cells.
Our recent findings demonstrate that levels and dynamics of E-cadherin alter in vivo gene expression largely by inhibiting Heterochromatin Protein 1 – a protein that is vital for the formation of transcriptionally inactive chromatin. Moreover, genes whose expression is altered by E-cadherin-dependent chromatin modulation are associated with cell differentiation, proliferation and apoptosis. In this project, the successful candidate will combine experiments in the genetically tractable Drosophila model with studies of human cells in culture to investigate:
- The molecular and cellular mechanisms by which E-cadherin-mediated cell-cell adhesion controls chromatin organisation
- The cellular and tissue-scale consequences of this control
The successful candidate will receive in-depth training in all required experimental techniques and data analysis. As the project progresses, the successful candidate will be encouraged to design and shape their own research agenda.
Funding
The studentship is funded by Queen Mary and will cover Home tuition fees, and provide an annual tax-free maintenance allowance for 3 years at the UKRI rate (£20,622 in 2023/24).
Eligibility and applying
Applications are invited from outstanding candidates with or expecting to receive a first or upper-second class honours degree and a masters degree in an area relevant to the project such as biomedical science, genetics, cell and developmental biology.
The ideal candidate should have:
- experience of microdissection, microscopy or immunohistochemistry;
- a good understanding of epigenetics, cell biology or related fields;
- an enthusiasm for learning and applying skills to study fundamental biological questions;
- excellent interpersonal and communication skills and ability to work in a collaborative environment.
Applicants from outside of the UK are required to provide evidence of their English Language ability. Please see our English Language requirements page for details: https://www.qmul.ac.uk/international-students/englishlanguagerequirements/postgraduateresearch/
Informal enquiries about the project can be sent to Dr Natalia Bulgakova at n.bulgakova@qmul.ac.uk
Formal applications must be submitted through our online form by 31st January 2024 for consideration, including a CV, personal statement and qualifications.
References
- Ramirez Moreno M, Stempor PA, Bulgakova NA. Interactions and Feedbacks in E-Cadherin Transcriptional Regulation. Front Cell Dev Biol. 2021 Jun 28;9:701175. doi: 10.3389/fcell.2021.701175.
- van Roy F, Berx G. The cell-cell adhesion molecule E-cadherin. Cell Mol Life Sci. 2008 Nov;65(23):3756-88. doi: 10.1007/s00018-008-8281-1.
- Du W, Liu X, Fan G, Zhao X, Sun Y, Wang T, Zhao R, Wang G, Zhao C, Zhu Y, Ye F, Jin X, Zhang F, Zhong Z, Li X. From cell membrane to the nucleus: an emerging role of E-cadherin in gene transcriptional regulation. J Cell Mol Med. 2014 Sep;18(9):1712-9. doi: 10.1111/jcmm.12340.