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Positioning of multiple cell types to investigate inter-cell communication

EPSRC Centre for Doctoral Training in Advanced Biomedical Materials

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Prof D Allwood No more applications being accepted Competition Funded PhD Project (Students Worldwide)
Manchester United Kingdom Biomedical Engineering Cancer Biology Medical Physics

About the Project

Application deadline: 3rd March

Interviews to be held: 31 March 2021

The first semester of this project will be based at the University of Manchester and the remaining duration will be based at the University Sheffield as this CDT is a partnership between the two universities.

Intercellular communication is a major factor for directing the control, development and response of eukaryotic cells in vivo. Examples include: in skin tissue, where models containing fibroblasts results in a more mature stratified keratinocyte epithelium; in neuroscience, neuronal and glial cell communication is responsible for growth and differentiation; and with cancer cells and host cells within the tumour microenvironment (TME), where communication can affect the behaviour of cancer cells and promote tumour progression by conferring cancer cells with the ability to migrate, invade, and metastasise. Furthermore, the system of neuronal and Schwann cells requires intercellular contact for Schwann cell myelination and differentiation.

There are, however, many unanswered questions about the nature of intercellular communication and existing co-culture models place cells randomly, making systematic study impossible. An improved understanding of intercellular communication will help uncover the tools used in cell-cell interactions and is essential for investigating cell evolution and dynamics (e.g. for nerve re-growth or understanding cancer growth). This understanding would also assist in the development of drugs to interrupt communication with diseased cells (e.g. cancer cells) to improve clinical outcomes.

A major obstacle to studying inter-cell communication quantitatively is a lack of suitable tools. The development of an appropriate platform to study cell-cell interactions promises to have widespread clinical impact relevant to a range of contexts, including neuronal function, tissue regeneration, cancer and stem cell differentiation.

Main question to be answered

The two main questions posed by this project are:

1. How can different cell types be positioned with defined proximity to each other?

2. To what extent does the cell positioning ability allow us to study inter-cell communication in clinically-relevant systems?

Answering Question 1 must consider that an ideal in vitro system should:

a. Allow different cell types positioning with pre-determined separation or contact

b. Be compatible with all cell types

c. Allow microscopy analysis of interacting cells

d. Support large numbers of cell interactions to create sufficient expressed factors for biochemical analysis

e. Be compatible with microfluidic systems

The project will investigate using patterns of magnetic materials and chemically modified regions of a surface to define trap locations for different types of cell. Previous studies have only ever considered one cell type at once, although these show that cell viability is generally good. 

Question 2 will be tackled using example cell systems, e.g. neuronal and Schwann cells, or human breast and prostate cancer cells with tumour-infiltrating primary host cells, including human endothelial cells, fibroblasts and immune cells. These will be co-cultured at different cell-type-separations and investigated either by microscopy (single cell pairs) or biochemically (large cm-scale arrays of traps). 

EPSRC Centre for Doctoral Training in Advanced Biomedical Materials

This project is part of the EPSRC Centre for Doctoral Training in Advanced Biomedical Materials. All available projects are listed here.

Find out how to apply, with full details on eligibility and funding here.

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