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We are all made up of billions of cells. We start out as one microscopic cell (the product of a sperm from Dad, fertilising an egg from Mum) and end up as a human being (coming in all shapes and sizes). All the cells in our body came about by cell division. Cell division is a series of complicated processes that all work together to precisely duplicate the cell - this is known as The Cell Cycle because it goes round and round and at least in cancer cells rarely stops. There is a cartoon of this shown below.

Click Here for larger image

 

Early in development cell specialise - some cells become brain cells (neurons), other become muscle cells (myocytes), other form the immune system etc. These then often group together and form an organ such as the liver or brain, skin, bone and so on.

Probably the most important aspect of the cell cycle is that the DNA - "the blueprint of life" - has to be replicated or copied so that the two new cells know what to do and what type of cell to be. The huge tangle of DNA in each cell (analogous to a tangled ball of wool) must be sorted out in order that the 2 copies of DNA are equally segregated to the new cells.

Nature had evolved a way of packaging the DNA efficiently - they are called chromosomes.

Chromosomes are hugely compacted DNA mixed with proteins.Click here to see what the DNA looks like when released from a chromosome. After they form they exist in pairs until they are pulled apart later in the cell cycle (see below). In a human cell there are 46. In bakers yeast there are 16. In some organisms there are just 3. In bacteria there is only 1. Dogs have 78

Each chromosome consists of a of a pair of sister-chromatids - exact copies of each other held together by molecular glue. When the cell has decided that it is happy that it has copied its DNA without making mistakes and that it has assembled its chromosomes, then the membrane around the nucleus breaks down, releasing all the chromosomes into the cell where they are free to float around.

This is dangerous situation if the cell want s to separate the sister-chromatids equally into two cells. How does it catch them and make sure they go to the two new cells? It does this using a structure called the mitotic spindle, which is a collection of protein tubes called microtubules that act like fishing lines to capture and "reel in" the chromosomes. The attachment process is set up such that each sister-chromatid has an microtubule attachment site - like a landing pad - called a kinetochore.

The spindle has two poles each acting as a microtubule organisng centre - some of the microtubules from opposite poles try to capture the chromosomes. Eventually all the chromosome will be attached to the spindle. Only when all the chromosomes have become attached to microtubules from opposite poles - a process called biorientation - do they move to the middle of the now roughly ball-shaped cell. This process requires lots of regulation and often goes wrong, leading to loss or gain of whole chromosomes (aneuploidy) .

This is bad for the cell as it may either die or eventually become cancerous.

The Aurora B protein kinase is a protein (enzyme) which adds a phosphate to target proteins and regulates their behavior. Aurora B is one of the ways the cell ensures this all goes to plan and that no errors occur. It regulates the function of many other proteins involved in cell divivion. We are currently trying to understand how this important protein works and which of the tens of thousands of the cells other proteins it regulates.

Once all the chromosomes are aligned in the middle the signal to go is released and the glue holding the sister-chromatids together is cut up with molecular scissors.
Then the pulling force of the microtubules drags each sister chromatid to a spindle pole (this phase is called anaphase). After anaphase of the cell cycle the cell has to divide itself into two. It does this by pinching itself in the middle (telophase) and then cutting itself into two separate cells each surrounding the separated DNA (cytokinesis).

Cytokinesis is also controlled by the Aurora B protein kinase.

Investigating how Aurora B works is critical to proprerly understand how cells divide.

The organism we use is cancer cells grown in culture and extracts from Xenopus frog eggs .

We use biochemistry, cell biology, molecular biology and microscopy to try to address these questions.

Three posters that went on display in the Sensation Science Centre in Dundee in 2004 and can be viewed by clicking here or on the image below. They accompanied a display of images and movies of cell division. They are aimed at 5-99 yr olds.

 

For a more detailed description of the research see the "Specialist" Research Page.

 

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© pdandrews 2004