Anne Skaja Robinson, chemical engineering, is the recipient of a National Science Foundation Career Award for her research into the molecular characteristics of damaged protein.

The NSF award totals $300,000 over four years with matching funds. Last, January, Robinson received the DuPont Young Professor Grant, which provided the matching funds needed for the first year of the NSF award.

With these two awards and other matching funds, Robinson was able to purchase two essential pieces of equipment, a thermocycler and a computer for performing kinetic modeling.

Because protein is one of the building blocks of all living cells, anything that keeps it from forming correctly can result in cell defects. In human beings, defective cells can lead to illness, disease and deformity; in the manufacture and use of drugs, damaged protein can inhibit potency and effectiveness.

Protein is made when long, linear chains of amino acids fold into precise shapes. If these shapes are formed properly, protein can carry out functions such as delivering oxygen to cells, strenghthening the immune system and helping break down food during digestion. Complex molecules called ribosomes guide the formation of linear amino acid chains from genetic messages within the cell. Sometimes, in the folding of the protein from its linear chain to its final shape, side chains are created and aggregate or cluster, causing a misfolding and a disfunctional protein.

The thermocycler replicates the chain reactions that produce the amino acid chain allowing researchers to see how changes to the DNA sequence affect damaged protein.

The computer will allow Robinson to examine the rate at which chain reactions take place so she and her students can determine at what point the cycle of misfolding begins.

In an article in the Massachusetts Institute of Technology's (MIT) magazine, Technology Review, molecular biologist Jonathan King predicted that "once the protein-folding problem is solved, major advances in human health and pharmaceutical production...should follow."

Robinson and her graduate students are working with a protein called the P22 tailspike, known to be especially susceptible to aggregation leading to misfolding. In her NSF application, she said that because misfolding in the tailspike protein is similar to other proteins, her findings could be widely applicable. Once they discover at what point in the process aggregation begins and at what rate it takes place, they will begin to develop strategies to inhibit and reverse the defect.

The UD researchers are attacking the malfunction on two levels.

First, they are using a method called mutagenesis, or the reprogramming of DNA to inhibit the tendency to aggregate and misfold before the bond is formed.

The second method deals with the protein after it has misfolded. This remedy could be used by the pharmaceutical industry in the manufacture of drugs. Robinson explained that they would apply hydrostatic pressure to the proteins in an attempt to correct the misfolds. Affected protein samples are put into a 1 1/4-inch thick metal cylinder filled with fluid. A pressure generator causes the fluid to infiltrate the samples, applying enough pressure to unfold the misfolded chains.

Robinson's research could lead to strategies for more effective drugs in the fight against cancer and other life-threatening diseases and help in controlling diseases such as cystic fibrosis, Alzheimer's and Parkinson's.

The NSF award also has an education component and is given, in part, to those who are working with graduate and undergraduate students. In her application, Robinson said that her ability to continue her research will affect the futures of the chemical engineering students who work with her and who want make biotechnology their careers. She said there is a growing demand for students trained "at the interface between biology and engineering."

Robinson joined the faculty of UD's engineering college in 1997. She received her undergraduate degree with honors from Johns Hopkins University, her Ph.D. in chemical engineering from the University of Illinois at Urbana-Champaign and did postdoctoral work in bioengineering at MIT, working with Jonathan King.

In addition to the NSF Career Award and the DuPont award, she has received an NSF POWRE Award, a National Institute of Health postdoctoral fellowship, the Clare Booth Luce Graduate Fellowship and a Department of Defense Graduate Fellowship.

–Barbara Garrison