Narrowing the Investigation

The initial whole-genome assay carried out by Whitehurst, which allowed researchers to determine the effect of each gene in the genome (over 20,000 genes) on chemotherapy resistance to the chemotherapy drug paclitaxel, resulted in a large number of genes that affect the resistance of cancer to chemotherapy. Many of the genes that were identified were involved in Mitosis, the process of cell division. These genes are used in every cell in the body during the Cell Cycle where the cell grows and divides. Because every cell uses these genes, it is not ideal to target these parts of the body, as they can cause side effects to normal cells, and we would prefer to focus on genes that are specifically used by cancer cells.

However, several of the genes that were identified are only expressed in Cancer Cells and the sex organs like the testes. These genes seem ripe for targetting because they are expressed in only a select number of tissues and should limit the potential side effects of drugs that target them. While all these genes are worthy of investigating at some point, to focus on only one at a time it is important to pick the gene that has the most effect on cancer cells.

Using a simulation, you can explore how to identify the gene that is most responsible for helping cells resist chemotherapy.

There are four plates to observe, and a comparison view. Each plate contains a number of dots, called wells, that contains a colony of cancer cells that have had one gene removed via RNA interference. Each plate contains the same sets of cells (dots in the same place on two different plates contain cells missing the same gene), but allows them to grow under different conditions. Growing conditions can be seen by mousing over the links, click the link to see the plate after reading the conditions. Think about the conditions the cells are growing in and try to determine which genes are granting the most resistance to chemotherapy before selecting the "compare plates" link.

So how does this experiment work? As discussed in Identifying Genes for Research a full gene assay tests every gene in the genome by seeing the effect of different conditions on the cell when the gene is manipulated as the result of RNA interference or Genetic Engineering . Cells in this experiment were missing genes, and those circled in blue are responsible for chemotherapy resistance. The missing gene in cells that die at the lowest concentration of chemotherapy are the ones that provide the greatest resistance, because all other surviving cells possess that gene and are able to survive.

After performing a series of experiments similar to the simulation you just completed, researchers identified a single gene, and therefore a single protein, to focus investigation on. The current research is attempting to understand how this gene/protein interacts with other parts of the cell. Gene / Protein Relationships are important for understanding all of the research that has occurred up until this point, and is especially important for understanding ongoing research. The Role of Proteins in the Cell is also important for understanding how proteins are responsible for Cancer's Properties.

Once the results of the assay were confirmed to apply to a wide range of cancer types and the genes that provided the strongest protection were identified, it was time to focus on the products of the genes and how they affected the cells. Without understanding the effects of the genes, making a drug to target them would be impossible. Because of this, ongoing research is focused on identifying Protein Targets as the active site for drugs.

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