How do individual histone modifications help cells make decisions?
We are looking for a highly-motivated, independent-thinking candidate to undertake a PhD project exploring the role of individual histone modifications in nuclear organisation, regulation of transcription, and the process of stem cell fate decisions.
The project is a collaboration between the Pina and the Bridger labs, with complementary expertise in stem cell biology, nuclear organisation, and single-cell techniques.
You will focus on the histone modifications effected by the epigenetic regulator KAT2A, and the large macromolecular complexes in which it exerts its activity - SAGA and ATAC (Arede and Pina 2021).
The Pina lab recently showed that KAT2A is required to maintain stem cells - normal and malignant - in an undifferentiatied state (Moris et al, 2018; Domingues et al, 2020). In its absence, stem cells start fluctuating their gene transcription and drift away from stemness into differentiation. Kat2a is responsible for acetylation of lysine 9 (K9) of Histone 3 (H3) - H3K9ac. Its macromolecular complexes, SAGA and ATAC, also participate in other histone modifications. In this project, you will be asking how the 2 complexes and their different modifications contribute to stemness through their roles in nuclear organisation and gene transcription.
You will combine CRISPR-Cas9 technologies, imaging techniques, and single-cell analysis to understand nuclear organisation, transcription and cell decision-making in 2D and 3D stem cell systems. If you are a keen lab worker, enjoy a technical challenge, and successfully persevere, we would like to hear from you. To apply, you will need to have a First or Upper Second-class BSc (Hons) degree or equivalent in Biology, Biomedical Sciences, Natural Sciences, Life Sciences, Genetics, Biochemistry or similar areas, and previous lab experience.
An MSc qualification is desirable but not essential. You will have excellent oral and written communication skills, and demonstrate the capacity to autonomously research, synthesise and critically evaluate relevant literature. You should be able to work independently and as part of a team, and have a dedicated and flexible approach to work.
How to apply
If you are interested in applying for the above PhD topic please follow the steps below:
- Contact the supervisor by email or phone to discuss your interest and find out if you woold be suitable. Supervisor details can be found on this topic page. The supervisor will guide you in developing the topic-specific research proposal, which will form part of your application.
- Click on the 'Apply here' button on this page and you will be taken to the relevant PhD course page, where you can apply using an online application.
- Complete the online application indicating your selected supervisor and include the research proposal for the topic you have selected.
This is a self funded topic
Brunel offers a number of funding options to research students that help cover the cost of their tuition fees, contribute to living expenses or both. See more information here: https://www.brunel.ac.uk/research/Research-degrees/Research-degree-funding. The UK Government is also offering Doctoral Student Loans for eligible students, and there is some funding available through the Research Councils. Many of our international students benefit from funding provided by their governments or employers. Brunel alumni enjoy tuition fee discounts of 15%.
Meet the Supervisor(s)
- I am a clinically-trained research scientist working in the field of cancer epigenetics. I am fascinated by the mechanisms through which cells diversify their molecular composition, and consequently vary their morphology and their function, to make organs, regenerate tissues, and produce tumours. While some of those diversification mechanisms rely on genetic mutations, others explore the way in which cells read their genes to produce the RNA and proteins that underlie cell function. The latter are referred to as epigenetic mechanisms.
My research is focused on understanding and manipulating epigenetic mechanisms to alter cell identity, and in particular, it aims to probe their role in cancer evolution in an attempt to unveil new therapies.
- I have been at Brunel University London since the start of this century. This is when I established my own independent laboratory - The Laboratory of Nuclear and Genomic Health. Our research concerns how the genome is spatially organised, influenced and manipulated within its environment, the cell nucleus. The group has had a number of major advances and is currently focused on aspects of genome behaviour in replicative senescence, the premature ageing disease Hutchinson-Gilford Progeria Syndrome, host:pathogen interactions and female cancers. We are wish to understand how structures such as the nuclear lamina, nucleoskeleton and nuclear motors influence the functionality of the genome.
I also teach Cell Biology at levels 2 and 3, Developmental Biology at level 2, Gene Expression and Epigenetics and Cellular and Organismal Ageing at Masters level. The lab is always full of PhD, Masters and undergraduate students doing their various projects.
I am also the Head of the Genome Engineering and Maintenance network established from the depth and interest in Genome Biology that has developed over time in Biosciences at Brunel. My other role is External Engagement where I organise all the external interactions we have in our division