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Clinically relevant mini-organs to identify optimal “chemo”-free treatments for childhood cancer Phase I trials (ref: RDF20/APP/PAL)

  • Full or part time
  • Application Deadline
    Friday, January 24, 2020
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

Better cancer therapeutics are urgently needed to maximise patient outcome. Cancer drug development is associated with the highest attrition rates thereby underscoring the immediate requirement for improved preclinical models. The aim of this interdisciplinary project is to integrate the disciplines of cancer research, regenerative medicine and tissue engineering in order to identify novel non-genotoxic treatments towards future Phase I trials.

This project will micro-engineer patient specific organoids (mini-organs) to model childhood malignancies of the bone and blood. Using induced pluripotent stem cell technology including stem-cell reprogramming and differentiation this project will develop patient specific preclinical models. Thus engineered 3D mini-organs will be validated through a combination of approaches with particular emphasis on reproducing clinically observed treatment response. Following clinical validation, key aspects of cancer cell behaviour such as malignant stem-cell quiescence will be defined in a 3D-patient-mini-organ setting. Experiments repeated under therapeutic pressure will specify mechanisms and signalling pathways regulating treatment response. These experiments will enable identification of novel single agent and combinatorial treatment regimens through an informed hypothesis-driven approach. Additional in silico dynamic modelling will further contribute towards prediction of optimal combinatorial synergies. Ultimately the overall aim is to develop a GLP compliant pipeline which incorporates in vitro and in silico approaches to prioritise optimal therapeutic combination strategies for future Phase I trials.

The successful applicant will be trained in a breadth of cutting-edge research methodologies including primary cell culture, induced pluripotent stem cell technology, organoid tissue engineering, cancer drug development and specialist molecular biology techniques. Training will further encompass GLP and industrial standard practices relevant for a career in the pharmaceutical industry. The doctoral training programme will further benefit from the lab’s extensive international collaborations with Newcastle University, UCL, The PMC, The Netherlands and the Wyss Institute at Harvard and links with local, national and international hospitals

Eligibility and How to Apply:

Please note eligibility requirement:

• Academic excellence of the proposed student i.e. 2:1 (or equivalent GPA from non-UK universities [preference for 1st class honours]); or a Masters (preference for Merit or above); or APEL evidence of substantial practitioner achievement.
• Appropriate IELTS score, if required.
• Applicants cannot apply for this funding if currently engaged in Doctoral study at Northumbria or elsewhere.

For further details of how to apply, entry requirements and the application form, see
https://www.northumbria.ac.uk/research/postgraduate-research-degrees/how-to-apply/

Please note: Applications that do not include a research proposal of approximately 1,000 words (not a copy of the advert), or that do not include the advert reference (e.g. RDF20/…) will not be considered.

Deadline for applications: Friday 24 January 2020
Start Date: 1 October 2020

Northumbria University takes pride in, and values, the quality and diversity of our staff. We welcome applications from all members of the community. The University holds an Athena SWAN Bronze award in recognition of our commitment to improving employment practices for the advancement of gender equality.

Funding Notes

The studentship is available to Home/EU students with a full stipend, paid for three years at RCUK rates (for 2019/20, this is £15,009 pa) and full fees.

References

1. Pal D, Blair HJ, et al. Long-term in vitro maintenance of clonal abundance and leukaemia-initiating potential in acute lymphoblastic leukaemia. Leukaemia 2016, 30, 1691-1700. Impact factor =12; citations = 18. F1000 prime recommendation obtained.

2. Martinez-Soria N.…Pal D…., Heidenreich O. The Oncogenic Transcription Factor RUNX1/ETO Corrupts Cell Cycle Regulation to Drive Leukemic Transformation. Cancer Cell 2018, 34(4), 626-642.e8.. Impact factor = 23.5. Citations = 12

3. Pal D*, Moad M*, et al. A novel model of urinary tract differentiation, tissue regeneration, and disease: Reprogramming human prostate and bladder cells into induced pluripotent stem cells. European Urology 2013, 64(5), 753-761. Impact factor = 17, citations = 60

4. da Conceicao Ribeiro, R.; Pal, D.; et al Reactive jet impingement bioprinting of high cell density gels for bone microtissue fabrication. Biofabrication 2018, 11 (1), 015014. Impact factor = 7.5

5. Ribeiro, R. D. C.; Pal, D.; et al. Temporary Single-Cell Coating for Bioprocessing with a Cationic Polymer. ACS Appl Mater Interfaces 2017, 9 (15), 12967-12974. Impact factor = 8.5

6. Weiland, J.; Pal, D.; et al. BCP-ALL blasts are not dependent on CD19 expression for leukaemic maintenance. Leukemia 2016, 30 (9), 1920-3. Impact factor = 12

7. Pal D, et al. Dormancy Stems the Tide of Chemotherapy. Cancer Cell 2016, 30(6),

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