Cellular Screening
One technique for discovering small molecules of biological relevance is to expose cultured cells to a variety of small molecules and look for changes in the cells' appearance, behavior or other measurable qualities.
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More About Cell Screen Background Advances in robotics and automation makes massive screening endeavors possible. The 384-well plate mentioned in the animation is standard laboratory equipment. In the video clip “Diversity Oriented Synthesis,” you can see many different types of automated equipment that handle transferring liquid to these plates, as well as to move and stack them automatically. Rapamycin is an immunosuppressive drug that has the side effect of causing Type II diabetes. More details of this condition can be seen in the animation "Rapamycin" Using Treated Cells to Screen for Small Molecules One technique for screening small molecules is to apply small molecules to cells in a culture to see what happens to the cell. In essence, you are perturbing the proteins in their natural environment, the cell. In this example, the objective is to screen small molecules for ones that interact with the glucose sensing protein network. Each well in the 384-well plate contains a small number of cells. The cells have been put into a “diabetic-like” state through the use of the small molecule rapamycin. Careful observation reveals that cells in this diabetic-like state look unhealthy (shown in pink). Each well receives a different small molecule from an automatic dispenser (represented by geometric shapes showering into the wells). Many of these small molecules have no effect on the cells, but one turns the cells from their diabetic-like state into a healthy state (shown in green). SMIR (small molecule inhibitor of rapamycin) was discovered this way. Cell Screen Background Advances in robotics and automation makes massive screening endeavors possible. The 384-well plate mentioned in the animation is standard laboratory equipment. In the video clip “Diversity Oriented Synthesis,” you can see many different types of automated equipment that handle transferring liquid to these plates, as well as to move and stack them automatically. Rapamycin is an immunosuppressive drug that has the side effect of causing Type II diabetes. More details of this condition can be seen in the animation Resources HHMI's 2002 Holiday Lectures on Science "Scanning Life's Matrix: Genes, Proteins and Small Molecules" Cell Screen Teaching Tips The animations in this section have a wide variety of classroom applications. Use the tips below to get started but look for more specific teaching tips in the near future. Please tell us how you are using the animations in your classroom by sending e-mail to biointeractive@hhmi.org.
Cell Screen Credits Director: Dennis Liu, Ph.D. Scientific Direction: Stuart L. Schreiber, Ph.D. Scientific Content: Satoshi Amagai, Ph.D. Animator: Eric Keller |