Don Arnold, associate professor of biological sciences in USC Dornsife, has received the 2012 McKnight Technological Innovations in Neuroscience Award.

The award supports scientists working on new and unusual approaches to understanding brain function. The program seeks to advance and enlarge the range of technologies available to the neurosciences and supports research based primarily on new techniques.

The McKnight Endowment Fund for Neuroscience is especially interested in how technology may be used or adapted to monitor, manipulate, analyze or model brain function at any level, from the molecular to the entire organism.

Arnold will use the award funding to study how intracellular antibody-like molecules called intrabodies can be used to target and eliminate proteins in living cells.

Eliminating a protein is a valuable way for researchers to understand its function. Current techniques to target proteins eliminate either the gene or the RNA that encodes a certain protein. These techniques effectively cut off the supply of new copies of a particular protein, so eventually the protein disappears.

However, intrabodies cause the elimination of proteins directly, which is much faster and more versatile than traditional nucleic acid-based methods for eliminating proteins.  Although intrabodies recognize specific proteins, like traditional antibodies, the peculiar way they are generated allows them to be modified to affect the target molecules  in different ways. For instance, they can be used to attach a fluorescent protein to the target allowing it to be seen, or they can be used to trick the cell into destroying the target protein.

Intrabody at work: (left) a cortical neuron in culture expressing the ablating intrabody; (middle) five hours after activation the intrabody target protein (shown in red) is almost completely eliminated from the cell; (right) a composite image of the left two panels shows that the remaining target protein is contained in the neurons, but not the neuron containing the ablating intrabody. Images courtesy of Don Arnold.

“It’s sort of the difference between a Word file and a PDF file,” Arnold explained. “An antibody is kind of like a PDF file: you’ve got it, but that’s it. You can’t do anything to it. Whereas the intrabody is like a Word document — you can modify it to do whatever you want.”

The technique Arnold will be investigating offers a faster way to target and remove degraded proteins in a cell or even in specific synapses in a neuron. Arnold can see a potential for using the technique in the study of neurodegenerative diseases such as Alzheimer’s, Huntington’s or Parkinson’s in the future.

Within USC Dornsife, Arnold has collaborated with Richard Roberts, professor of chemistry, biological sciences, and chemical engineering. Applying a method Roberts developed for generating intrabodies, called mRNA display, Arnold’s lab established a way to make them work within neurons.

Arnold said that receiving the award opens a world of opportunities. Each year, the McKnight Endowment Fund for Neuroscience hosts a conference that brings together past and present awardees, who brainstorm ways to solve problems in neuroscience.

“There is an incredible group of scientists who have won this award in the past,” Arnold said. “It’s great to be part of the group and to have an opportunity to interact with them.”