The role of the cytokine interleukin 1 beta in shaping the neoplastic and immune cell landscape in Glioblastoma

Closing date: 25/03/2024

MB-PhD Project: The role of the cytokine interleukin 1 beta in shaping the neoplastic and immune cell landscape in Glioblastoma

Lead Supervisors: Prof. Kevin Couper
Co-Supervisors:
Prof. David Brough, Prof. Petra Hamerlik, Prof. Kaye Williams, Prof. Robert Bristow

Applications Deadline: Monday 25 March 2024

Project Keywords: Brain tumour; Neuro-immunology; Immunotherapy
Research Opportunity: Intercalated PhD, leading to the award of PhD and MBChB

The project supervisor is offering a PhD in the below area during 2024/2025. Work during the Summer Placement might involve some of this work but could vary.

Project Outline

Glioblastoma is the most common type of malignant brain tumour. They are highly aggressive tumours and are generally incurable, with a mean survival time following diagnosis of only 12-18 months. As such, new treatments for glioblastoma are urgently needed.

Glioblastoma tumours are extremely heterogeneous, being comprised of various distinct tumour regions (niches), each of which have different biology and which can exhibit divergent responses to treatment. It is this intra-tumour heterogeneity that makes glioblastoma so difficult to cure.

In this project, you will investigate how immune pathways, in particular the pro-inflammatory cytokine IL-1B, promotes intra-tumoral spatial heterogeneity and the formation of distinct tumour niches within glioblastoma. Specifically, you will address how IL-1B promotes intra-tumoural hypoxia, and the establishment of immunosuppressive tissue niches.

Hypoxia is induced when tissue and tumour regions are starved of oxygen. This leads to the recruitment of pro-tumour immune cell populations, and pathologic immune cell- neoplastic cell communication in the tumour, which shortens survival. You will work on an interdisciplinary programme of work where you will utilise cutting edge high-dimensional imaging approaches combined with transcriptional profiling to analyse the localisation and activity of IL-1B in hypoxic and immunosuppressive niches within human glioblastoma samples. You will complement this with detailed mechanistic investigations using in vivo models of glioblastoma (which are selected to optimally reflect human disease), to analyse how IL-1B is activated and produced within the tumour. 

You will subsequently examine how manipulation of the IL-1B pathway alters the tumour spatial architecture and hypoxic niche formation, modulating the progression and treatment response of glioblastoma. Collectively, the project will provide experience in cancer immunotherapy and will offer training in cutting edge neuro-oncology and immunology methodologies and technologies, including experience of in vivo experimentation 

About Prof. Kevin Couper (project Lead Supervisor)

Kevin is a Professor of Immunology based within the Lydia Becker Institute of Immunology and Inflammation and the Geoffrey Jefferson Brain Research Centre.

Kevin’s main research interests include:

  • Malaria Pathogenesis – Kevin’s research group use murine models of malaria and human blood and tissue samples to investigate the parasitological and immunological processes that initiate and cause severe malarial disease.
  • Understanding the immune response to brain tumours – Kevin’s research group work closely with pathologists and neurosurgeons within the Geoffrey Jefferson Brain Research Centre and employ cutting-edge high dimensional imaging approaches to study the cellular landscape within different types of brain tumour.

Find out more

Headshot of Prof. Kevin Couper

About the lab group

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