The small molecule 'furrowstatin' exemplifies the power of using small molecules to investigate life's processes. When applied to dividing cells, the furrowstatin halts cell division.
More About Furrowstatin
Furrowstatin is a molecule that was created by diversity-oriented synthesis. It has an interesting property of interfering with the formation of a cleavage furrow during cell division.
This series of three video clips illustrate the power of a chemical genetics approach when investigating a dynamic process such as the cell division.
Part 1: The cleavage furrow
The cell in the top-right corner is about to undergo cell division. In this example, the formation of a cleavage furrow prior to cell division can be seen.
Part 2: The addition of furrowstatin arrests furrow formation
The two cells in the center of the screen are about to undergo mitotic cell division. The upper cell is in metaphase, the lower cell is in prophase. Notice the clearly visible chromosomes. The blue tint that covers the screen represents the addition of furrowstatin. Note that the formation of the cleavage furrow in the upper cell, which normally pinches off and divides the cell in two, is frozen at the instant of furrowstatin addition. The upper cell is frozen during furrow formation and never completely separates. The lower cell never forms a cleavage furrow, yet proceeds through anaphase and telophase and chromosome separation.
Part 3: Furrowstatin's effect is reversible
This movie illustrates that furrowstatin’s effect is reversible. The cells start in the presence of furrowstatin, represented by the blue tint covering the screen. The cell in the center is undergoing cell division and its chromosomes separate to opposite ends. The cell division is arrested because the cleavage furrow cannot form. After furrowstatin is washed away, represented by the removal of the blue tint, the cleavage furrow forms and the cell divides.
During the final stages of cell division, after the chromosomes have been segregated, a contractile ring forms near the metaphase plane and pinches off the cell in two. This structure is known as the cleavage furrow. The small molecule called “furrowstatin” has the interesting property of halting the process of the cleavage furrow formation. Depending on when furrowstatin is added, it can prevent the formation of the furrow, or arrest the pinching process. All other stages of cell division proceed normally. The effect is reversible; if furrowstatin is washed out, the cleavage furrow will pinch off the cell normally.
The chemical genetic approach uses small molecules to investigate a life process by perturbing the protein directly. This approach has advantages over the conventional genetic approach of using mutations to disrupt a gene’s function. One advantage is that small molecules can be added to cells with temporal precision, so that information about a dynamic process can be gained by perturbing the protein at different times. In contrast, mutation is in effect constantly, and it is not always easy to see what part of the process is being affected. Another advantage is that small molecule perturbations are often reversible, allowing a comparison of the process before, during, and after the perturbation.
Furrowstatin 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 firstname.lastname@example.org.
Use the animations to make abstract scientific ideas visible and concrete.
Explain important scientific principles through the animations. For example, the biological clocks animations can be used to demonstrate the fundamentals of transcription and translation.
Make sure that students learn the material by repeating sections of the animations as often as you think necessary to reinforce underlying scientific principles. You can start, restart, and play back sections of the animations.
Urge students to use the animations in accordance with their own learning styles. Students who are more visually oriented can watch the animations first and read the text later, while others might prefer to read the explanations first and then view the graphics.
Incorporate the animations into Web-based learning modules that you create to supplement your classroom curricula.
Encourage students to incorporate the animations into their own Web-based projects.
HHMI's 2002 Holiday Lectures on Science "Scanning Life's Matrix: Genes, Proteins and Small Molecules
Director: Dennis Liu, Ph.D.
Scientific Direction: Stuart L. Schreiber, Ph.D.
Scientific Content: Satoshi Amagai, Ph.D.
Animator: Chris Vargas