Using laboratory models to test the effects of foods
One way of testing food compounds is by using laboratory models.
As part of the nutrigenomics project, researchers are trying to identify food compounds that are likely to be especially helpful (or harmful) for people with particular genetic combinations.
One of the ways they did this was by using laboratory models.
Why are laboratory models needed?
It would be inappropriate to directly test the effects of different food compounds using people. There are several reasons for this.
Firstly, it would be difficult to monitor the effects of only the food compounds, and not any other environmental factors (the person would have to live in a controlled environment for the duration of the experiment).
Secondly, all research needs to be repeatable. Because the way we respond to food is controlled partly by our genes, researchers would need to find several people who had exactly the same genotype. This would be impossible, as only identical twins have the same genes.
Thirdly, there are thousands of food compounds. You would either need a huge number of willing participants (all with the same genotype) to be able to test all the foods, or you would need to involve each person in a very long-term study (to test all the food compounds in isolation).
Then there are the ethical issues. No-one would agree to participate in the experiment unless they were assured that the tests were unlikely to cause significant harm. The researchers would not be able to guarantee this unless they already knew a lot about the responses that the food compounds are most likely to cause.
What are cell lines?
One way that the interactions between food and genes can be studied in a laboratory is by using a cell line. A cell line is a group of cells that grow and replicate continuously in vitro in a laboratory.
Cell lines: What are they?
Normally, cells from your body die after a certain length of time. They have an in-built suicide mechanism. This is natural. Cells that are used for cell lines need to keep growing forever. They have to be immortalised.
The cells can keep growing forever as long as they are provided with sufficient nutrients, but they will always only be individual cells. They will never be able to grow back into a whole organism.
Cells in a cell line are immortal. They will keep growing for as long as they have sufficient nutrients. However, they will always only ever be individual cells. They will never be able to grow to become a whole organism.
Why are cell lines useful?
Cell lines are useful for research because every cell in a cell line has identical genes (all the cells originate from one cell). This means that they should all respond in exactly the same way to a particular treatment, allowing for repeatability.
Cell lines and immortal cells
Dr. Martin Philpott from Auckland Medical School explains that cell lines are made from cells that are immortal, or don't die. An example of an immortal cell is a cancer cell. It keeps growing and dividing uncontrollably. It does not have the triggers that cause it to die.
In addition, different groups of cells from a cell line can be used for testing different molecules.
In the case of nutrigenomics, the effects of food compounds are tested. By using a cell line, a huge number of different food compounds can be tested in a relatively short time.
How are cell lines used in nutrigenomics research?
In the nutrigenomics project, cell lines will be used to test the effects of thousands of different food compounds. The cell lines need to behave as closely as possible to cells from a person who has a particular genetic predisposition.
The New Zealand researchers are first studying the effects of different foods on people who have inflammatory bowel disease (IBD).
The cell lines that are used to test the foods need to behave as much as possible like cells from someone who has IBD.
Genetic engineering techniques are used to insert copies of gene variants associated with IBD into the cells.
Remember, though, that these cells will never be able to be anything other than individual cells. They cannot grow into an organism.
The need for reporter genes
Cells are tiny and can usually only be seen with a microscope. It is even more difficult to tell what is going on inside cells. The researchers need to have a way of measuring the effects that the food compounds have on cells.
Using reporter genes in research with cell lines
A great deal of research in the Nutrigenomics Project is carried out using cells that are too small to see. Dr Martin Philpott of Auckland Medical School explains how you can measure the ways that these cells respond to different food molecules.
In the Nutrigenomics Project, cell lines have been developed that mimic a disease situation. Different food molecules are then added to the cells to see what effect they have. One way of measuring the effects of the food molecules on the cells is to add a 'reporter gene' to the cells. The reporter gene will be turned on or off depending on the cell's response to the food molecule. In this case, the reporter gene is a gene from fireflies. It is called the luciferase gene. When the gene is turned on, the cell will glow. The glowing tells researchers what sort of effect the food molecule has had on the cell. In these cell lines, increases in inflammation cause the luciferase gene to be turned on, and the cell to glow.
A reporter gene is inserted into the cells. The reporter gene is selected because of its ability to produce a reaction that researchers can measure. Often the luciferase gene is used. This is a gene that is found in fireflies. It causes luminescence, or glowing, when it is activated. Researchers can tell the effect that a food compound has on a cell by whether or not the cells glow. The amount of glowing is measured by a machine called a luminometer.
Limitations of cell lines
A cell line will not behave exactly in the same way as cells that are part of a whole body. However, the results from the cell line tests allow researchers to make better predictions about the effects food compounds might have on people with particular genes.
Other laboratory models
Laboratory animals can also provide a useful way of testing the effects of foods. Rats and mice are particularly useful because they reproduce very quickly.
Planned breeding programmes can ensure that the mice have particular genetic characteristics (something that can’t be done with human participants). Inbred strains allow for replication of experiments.
Environmental factors can also be easily controlled (compared with controlling the environment of a human participant).
All research carried out using animals needs to be done according to strict ethical guidelines. This is to protect the welfare of the animals.
