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Single Cell Sequencing

Recent technological developments have led to a new understanding of cancer. It was believed that tumours were masses of identical or similar cells, and treatment has reflected this idea. New technology has enabled analysis at the level of individual cells, rather than being restricted to assessing a whole tumour. This has revealed that tumours are made up of mixed populations of cells, which vary between each other to a degree that could never have been predicted. The relationships between neighbouring cells may hold crucial answers as to how cancer develops and spreads, and how to design new diagnostics and treatments.

The DNA damage pathway

In order for cancer to form, DNA damage must occur. However, it is not understood how cells respond to DNA damage, and this process has never been assessed at the level of single cells. Action Against Cancer is funding pioneering research examining cells one by one to identify the DNA damage pathway in tumours.

To do this, the team are examining RNA (ribonucleic acid), which is formed in the nucleus of cells. RNA is often described as a messenger, as it rewrites a small section of DNA in a process called transcription, and carries this code for building a specific protein to other parts of the body. It is thought that these proteins are responsible for the structures and functions we are familiar with, such as brown hair or blue eyes etc.

Cells have been found to be malignant at various stages of the process of transcription from DNA to RNA. Recent findings within the science community have shown that these malignant cells can be harboured within tumours.

Pioneering project

Building on this work, a team of scientists working in Professor Justin Stebbing’s group at Imperial College London, are working on the first study of its kind undertaken in the world. Using state of the art genetic sequencing technology to study RNA cell by cell, the aim is to understand the role of DNA damage in the growth and spread of cancer, and to develop a new treatment.

Progress so far: gene discovery

Preliminary data has been obtained by processing 160 individual cancer cells for genetic sequencing. The samples were stimulated to cause DNA damage, and the cells response in terms of gene expression analysed on a cell by cell basis. As suspected, it was discovered that cells do not make a uniform response to such damage, but that some are early and some are late responders. Now it has to be determined how each cell makes this kind of ‘decision’.

Excitingly, the team believe they have made a breakthrough discovery by identifying one gene in particular, which seems to orchestrate the cells response to DNA damage. They have done this by making complex maps from their experimental data to find which genes are expressed together. The challenge now is to develop cells where this orchestrating gene has been “knocked out” to form a target for future diagnostics and treatments.

Diagram of Single Cell Sequencing
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Diagram of Single Cell Sequencing