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Research Using Suppression Genetics

 

Taylor Allen: Still Looking at Worms--with New NSF Grant to Fund His Research on Muscle Function
(Main Story)

Scientists know that troponin I prevents contact between thick and thin filaments in the absence of calcium, Allen says, but the interactions troponin I makes remain unclear.

One approach that students will use to find out is called suppression genetics.

In the first phase of the suppression-genetics experiment, the researchers will engineer single mutations into specific regions of troponin I in populations of worms. Each mutation will be designed to cause abnormal muscular function.

In the second phase, the researchers will administer a chemical mutating agent to the worms whose muscular function has been compromised by the engineered mutation. Exposed to the chemical, some of the worms will regain normal muscular function because the chemical will induce a second mutation that either suppresses or compensates for the first mutation.

The students will then look at the worms in a microscope to observe their movement, and pick out the worms that seem to be functioning normally.

They will isolate the DNA of the picked-out worms and examine it to see where the pattern of the DNA sequence differs from the DNA in worms that have undergone no mutations. The site of DNA alteration will identify which gene has been affected by the chemical mutagen.

When they know which gene has received the second mutation, they can infer which protein is involved because specific genes make specific corresponding proteins. But the experiment identifies far more than just the protein that interacts with troponin I, says Allen. "It actually pinpoints the exact part of the protein that interacts with troponin I."

Allen and his students are interested in the proteins--and specifically the troponin I interactions--because proteins perform the activities of the cell, and therapeutic drugs can be designed to interact with the proteins.

Understanding the interactions that troponin I makes could help scientists design drugs to treat deteriorated functioning in such important human muscles as the heart.

 

 

 

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