"When these proteins bind to their target sites, they undergo massive changes in molecular shape," says van der Vaart. "They often fold and bend or kink the DNA. It is not understood how the folding, bending and binding are coupled, and it is not understood what interactions trigger this behavior. My research aims to address why these changes happen and determine the molecular cause of this very complex process."
Van der Vaart will focus on two representative systems -- the Ets-1 transcription factor (which is involved in embryonic development, angiogenesis and cancer), which partially unfolds upon binding and bends the DNA by 26 degrees; and the lac repressor headpiece (part of a much larger bacterial protein), which folds upon binding and bends the DNA by 36 degrees.
Computer simulations will give insight into how the molecular recognition processes are coupled to conformational dynamics. The knowledge gained is expected to lead to a better understanding how proteins and DNA interact. In the long term, these will ultimately help to understand how important cellular processes are initiated (in sick or healthy cells).
The program will include the mentoring of minority undergraduate summer students, the development of new high school teaching modules, and the introduction of visualization labs in the classroom.
The Career awards are an example of the economic benefit a research university can bring to its state. Each year, Arizona universities contribute nearly $1 billion into the Arizona economy from their research, most of which is funded by the U.S. government and entities from outside the state. Res
|Contact: Skip Derra|
Arizona State University