Black Leaders in Cancer PhD Programme (Leo Carlin)

Cancer Research UK
November 25, 2024
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Offerd Salary:£21,000
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Job details

Job title

Black Leaders in Cancer PhD Programme (Leo Carlin)

Job reference

REQ00366

Date posted

21/10/2024

Application closing date

25/11/2024

Location

Glasgow

Salary

Stipend - £21,000 per annum

Package

All tuition fees will be covered

Contractual hours

Blank

Basis

Blank

Job category/type

PhD Students

Attachments

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Job description

The role of extramedullary granulopoiesis in pancreatic cancer progression

and spread

Background

Neutrophils are essential immune cells for anti-microbial defence and neutrophil defects leave the host critically immunocompromised. However, recent work has revealed that these leukocytes also play important roles in cancer with both potent anti- and pro-tumour activity. Neutrophils have been found to be potently pro-metastatic in models of colorectal, breast, and most relevant to this project, pancreatic cancer.

Recent work has established that there is a much higher degree of heterogeneity in neutrophil phenotype than was previously appreciated. This plasticity is surprising on one level due to the relatively short life of the cells, but on another level, we now understand both heterogeneity in ontogeny and environment-driven plasticity to be a key feature of other myeloid cells.

Neutrophil heterogeneity can be both regulated at a systemic level and local level, due to changes in neutrophil production (e.g. “emergency granulopoiesis”) and tissue imprinting. Our own work has uncovered features consistent with extramedullary granulopoiesis within liver tumours as well as highlighting the spleen as a relevant extramedullary production site in cancer capable of producing neutrophils distinct from those that originate in the bone marrow.

Research question

This project will build on previous work in our labs and others, and use sophisticated, disease positioned mouse models to interrogate the role of neutrophils produced outside of the bone marrow in pancreatic cancer progression and metastasis.

Skills/techniques that will be gained

The project will use advanced techniques to:

  • Elucidate the localisation and identity of neutrophil phenotypes in pancreatic cancers, the spleens of tumour bearing mice, and metastases using scRNAseq , spatial transcriptomics and multiplexed immunofluorescence in gold-standard autochthonous spontaneously metastatic mouse models of pancreatic cancer exploiting a wealth of archived tissue spanning multiple organs and stages of disease.
  • Use multiplexed live tissue imaging and intravital microscopy to monitor neutrophil behaviour and cell: cell interactions directly focusing in on particular sites and timepoints.
  • Exploit high parameter spectral flow cytometry to understand temporal shifts in neutrophil phenotype during the progression of cancer.
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