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DNA, Single Cell Biology

Why one cell is better than 40,000,000,000,000

Your body is a mass of millions and millions of tiny building blocks called cells, which all work together seamlessly on a daily basis in order to allow you to eat, drink, sleep, work, consume caffeine and perform all other essential bodily functions. A major outstanding question in the biological sciences is how these cells behave individually, but until recently scientists have not been able to isolate and analyse these tiny tiny entities on their own. However, huge technological advances in recent years mean that finally this is now possible, and in this blog post Martin Larke explains how scientists at the WIMM plan to use these new methods to ask previously unanswerable questions.

It is estimated that the average human body is made up from nearly 40 trillion individual cells. This colossal population originates from just one single cell, the embryonic stem (ES) cell, which is formed by the fusion of a male sperm cell with a female egg cell.

Encoded in its DNA, an ES cell contains the instructions on how to build an entire human being and is capable of producing any type of cell in the body.

In order for this process to occur, however, certain sets of instructions (or genes) must be switched on or off as the ES cell grows and divides. In this way ‘daughter’ cells can be formed which have specific genetic profiles that differ from their parent cells. These profiles determine what specialised function the cell performs.

Until recently much genetic research has focussed on analysing the genetic material taken from tissue samples such as blood. These tissues are made up from millions of cells, which together can perform diverse functions such as (in the case of blood) transporting oxygen around the body or fighting infection by viruses and bacteria.

A microfluidics device shown in comparison to a match.

A microfluidics device shown in comparison to a match.

Scientists have made much progress in understanding which groups or populations of cells perform specialised functions as a tissue, but we are still left with a big question: how do we know if each individual cell in a population is using its genetic information in the same way?

A useful analogy to understand this phenomenon is life expectancy. The average life expectancy in the UK is 81 years, so at the population level we could say that British people live to be 81. However, although some people will live to or exceed this age, others may die younger. Therefore we can see at the level of the individual the behaviour is very different from the population average.

This is exactly the same case when looking at the levels of gene activity in cells. The fine detail of what is happening in individual cells is masked or covered up by the average population activity of all the cells.

However recent technological advances are allowing us to take a much deeper look into what is happening inside individual cells within a population. Funded by the MRC’s Clinical Research Capabilities and Technologies Initiative, the WIMM has recently established a new single cell facility as part of the Oxford Single Cell Biology Consortium.

This state of the art facility allows the analysis of individual cells by using a technology known as microfluidics. In this process a solution of many cells is passed through microscopic capillaries (tubes), which are often thinner than a human hair. The capillaries act like a sieve, only allowing cells of a certain size to pass through and reach a collection point. Then a microscope is used to ensure that only one cell has been collected per collection point.

To generate a genetic profile of each individual cell a chemical chain reaction known as PCR is performed, which generates a million copies of the genetic material inside the cell which is otherwise present in vanishingly small amounts. PCR itself can be used to detect changes in the DNA sequence but is limited to studying a maximum of a few tens or hundreds of changes at once.

An alternate approach still uses PCR to generate more material for analysis but follows this with high-throughput DNA sequencing, a process which allows scientists to read the entire genetic code at once, and therefore examine thousands of genes or changes in the DNA at the same time. This generates a genetic profile for the cell, which then can be compared between abnormal (for example cancerous) and normal cells or between people affected by a particular genetic disease and those who are unaffected.

In this way scientists, identify changes to the DNA that could be linked to the cause of the disease. With 40,000,000,000,000 cells to analyse per person this sort of high-throughput DNA analysis is not a trivial undertaking, but learning how individual cells work together to form and maintain our bodies will greatly help us to understand how genetic diseases such as cancer occur and how to better treat and prevent them in the future.

Post edited by Bryony Graham.

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