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Investigating KAT2A as a novel therapeutic target in neuroblastoma


   Biosciences

  ,  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

The Pina lab is looking for a highly-motivated, technically-able and independent-thinking candidate to undertake a PhD project researching the role of histone acetyl-transferase KAT2A in neuroblastoma.

The project will be supervised by Dr Cristina Pina (https://www.brunel.ac.uk/people/cristina-pina), in collaboration with Professor Arturo Sala (https://www.brunel.ac.uk/people/auturo-sala).

The Pina lab specialises in epigenetic and transcriptional regulation of normal and malignant stem cell fate decisions, and has an interest in the role of histone acetyl-transferase KAT2A in cancer. The group has previously characterised KAT2A as a vulnerability in Acute Myeloid Leukaemia (Tzelepis et al, 2016), its loss resulting in progressive depletion of leukaemia stem cells (Domingues et al, 2020). KAT2A exerts its effects through 2 distinct complexes, SAGA and ATAC, which respectively control cell differentiation and biosynthetic programmes (Arede and Pina, 2021).

The Sala group has been involved in neuroblastoma research for over 20 years, contributing to the identification of oncogenes and tumour suppressor genes relevant to this cancer (Chaika et al, 2009; Chaiwatanasirikul and Sala, 2011; Corvetta et al, 2013; Dvorkina et al, 2016).

Neuroblastoma is the most common solid tumour in children under the age of 5. It has a poor overall 5-year survival of <75%, which drops to <60% in high-risk disease. High-risk disease is associated with amplification of the MYCN gene, which has been shown to partner KAT2A during development of the nervous system. Preliminary data from our group suggests that inhibition of KAT2A kills neuroblastoma cells with MYCN amplification, and may constitute a novel therapeutic strategy in neuroblastoma.

In this project, you will use chemical and genetic ablation of KAT2A, and of components of SAGA and ATAC complexes, to dissect the cellular and molecular mechanisms by which KAT2A complexes sustain neuroblastoma cells. You will use 2D and organoid-culture systems and employ transcriptional and chromatin analysis tools to analyse MYCN amplified and non-amplified cell lines and primary neuroblastoma samples, and to target differentiated and stem-like neuroblastoma cells.

If you are a keen lab worker and passionate about cancer research, 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.


Funding Notes

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: View Website. 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%.

References

Arede and Pina (2021) doi: 10.1016/j.exphem.2020.10.003
Chaika et al (2009) doi: 10.1093/jnci/djp063
Chaiwatanasirikul and Sala (2011) doi: 10.1038/cddis.2011.99
Corvetta et al (2013) doi: 10.1074/jbc.M113.454280
Domingues et al (2020) doi: 10.7554/eLife.51754
Dvorkina et al (2016) doi: 10.1158/1078-0432.CCR-15-2081
Tzelepis et al (2016) doi: 10.1016/j.celrep.2016.09.079

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