Identifying Genes for Research

When tackling an organism as complicated as the human body, and when dealing with a disease as complex as cancer, the number of things interacting to cause the disease is very large. Once upon a time, it would have taken researchers several lifetimes to sort through all the proteins and chemicals in the cell and figure out every interaction in hopes of understanding the process, or hoping that they got lucky somwhere along the way, and designing drugs from that point, . Thankfully, advances in technology help science progress at a much faster rate, and researchers around the world (including the Whitehurst laboratory here at UNC) are using techniques that allow them to quickly and easily learn new things about the cells in our bodies. One of the powerful biotechnologies that has helped the study of cancer and drug development is the develoment of screening.

Screening for Answers: Whole-genome assay

Screening technology has advanced quickly in the past decade to allow for thousands and millions of experiments to be carried out in an extremely fast manner. From this technology the whole-genome assay was developed. This is essentially a very fast method of performing an experiment on every gene in a cell to look for a reaction. The following small simulation puts you in charge of the experiment to determine which genes are involved in making cancer resistant to a chemotherapy drug called Paclitaxel, just as the researchers originally did.

There are three 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 related to resisting cancer before selecting the "compare plates" link.

So how does this experiment work? The process involves taking a large plate containing a bunch of small wells containing cancer cells . Each small well, represented as a dot, has siRNA added to the cells in it to cause RNA interference which turns off a single gene in the cells. This gives you a huge number of cells missing different genes and allows you to perform many experiments at once. Since some genes are necessary to survive, the ones necessary to make energy for instance, cells missing those genes will die even under the best conditions (the control plate). Other genes are not needed under the best conditions, but are helpful in resisting chemotherapy. Therefore, cells missing those genes would only die under conditions where at least some chemotherapy is present. Even though we do not know what genes do from these experiments, we can still determine which genes are needed for cancer to resist chemotherapy. It is important to note that the dosage of paclitaxel in the "test plate" is not a full dose. Therefore, cancer can be treated using a much lower dosage of chemotherapy if combined with a drug that eliminates one of the genes identified in the screen, or treatment with a drug and a full dose of chemotherapy could be used to kill even the most resistant cancer cells.

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