Making proteins in the lab
Proteins are produced by living cells and have a huge number of different functions. They act as transporters and messengers around the body, control growth, help keep us healthy, and are the building blocks for body parts like muscles.
If we could make these proteins in large amounts in a lab, they could be used for a huge variety of different purposes.
Producing proteins in a lab
All living organisms contain in their cells. This DNA is the code (or instructions) that cells use to make proteins.
The structure of DNA has been known for over fifty years, but it has taken time to work out what it does – and how it can be used in industrial applications. A breakthrough came in 1972, when Paul Berg explained how to cut and paste DNA from a bacterium into a . This had wide applications. If you could transplant DNA, you could make proteins to order !
This process of transferring DNA from one to another is called . The cell containing the foreign DNA is called a recombinant cell.
Making insulin
One of the first breakthrough uses of this technology was to produce large quantities of , a that is needed to treat diabetes. Before then, the insulin came from pigs, cattle and human cadavers. Insulin is made in the pancreas of humans, but pancreas cells are difficult to grow outside the human body. In contrast, Escherichia coli , which is a rod-shaped bacterium found in intestines, is very easy to grow in large quantities in a lab. Scientists were able to transfer the needed to make insulin into the . In 1982, insulin produced by genetically engineered E. coli was approved for use with patients.
Solving the problems
It sounds easy. Find the protein that interests you. Find the gene (in the DNA) that is needed to produce it. Take the DNA and paste it into a helpful bacterium, and then produce any amount of the protein you like. Although this is a good idea it has many practical difficulties.
Yusuf Chisti and a bioreactor
Professor Yusuf Chisti with a bioreactor machine.
One of the difficulties is that bacterial cells and mammalian cells produce different types of proteins. In mammalian cells, many of the proteins get carbohydrates added to them. This doesn’t tend to happen in bacterial cells.
To produce many mammalian proteins properly, you really need mammalian cells – but mammalian cells will divide only so many times before they die. You can get around this fusing a cell with the cell that produces the protein that is wanted to create a specific 'cell line'. This fused cell is called a hybridoma. It will go on living and dividing (and producing the protein you want) long after an ordinary mammalian cell would have died. This is all done . Special growth solutions are needed to provide the cells with all the nutrients they require.
A second problem is that cells make a huge range of different proteins. Harvesting the protein that you want requires many separation steps, so that the protein you want can eventually be isolated in pure form.
Growing the cells
The cells that are going to produce the protein you want need to be able to be grown in large amounts. Bioreactors are used to grow cells under conditions where they will make proteins. A provides cells with all the substances they need to grow and reproduce.
Creating the perfect environment
One of the important jobs for the biotechnologist is to create the perfect environment for the cells to grow and thrive. Nutrients and oxygen must be delivered in exact quantities, the temperature and must be maintained, and waste products must be removed. The cells are very picky about their living conditions.
Sometimes, the perfect environment to grow proteins is in space. The pull of gravity can distort and limit the growth of protein crystals. Growing them in microgravity produces larger, more-perfect crystals.
Current New Zealand examples
and are working together to produce several different types of proteins in their labs. is a world expert in this area.
Vaccines to control disease
In one bioreactor that technicians look after, bacteria are dividing and growing in a milky, nutrient-rich broth. These bacteria are being used to make a specific antigen. An antigen is any substance that causes the to produce antibodies. When an animal is injected with the antigen, antibodies are made that can ‘fight off’ or protect the animal from . This is what happens when you are vaccinated. In this particular case, sheep that are injected with the protein made by cells in the bioreactor will develop to hydatidosis. This is a disease that is caused by a worm that can also infect and kill humans.
Hormones to affect fertility
In another bioreactor, genetically engineered is producing follicle-stimulating (FSH). This hormone can be used to cause ‘superovulation’, or the development of more than the usual number of eggs in female mammals. This can be used to help females who have trouble getting pregnant.
Source: Wood, Malcolm. How to be the perfect
