Student Sarah Kurian assists chemistry professor Andrew Mehl

Biochemist Receives Grant from National Science Foundation

Research may lead to treatment of disease

March 10, 2010

Knox College has been awarded a National Science Foundation grant of more than $26,000 for research equipment in chemistry and biochemistry. The grant to Andrew Mehl, professor of chemistry, supports purchase of a "stopped flow" apparatus that works with the College's Olis spectrophotometer to monitor extremely fast chemical reactions and biological processes.

Mehl and his students are using the device to investigate the structure of proteins -- biological molecules made up of long chains of amino acids that take on complex folded shapes when they are created within organisms. "Our study of protein folding is basic science research that will help us understand how proteins are formed, and how that formation affects their function," Mehl says. "The problem is that  folding of most proteins takes place in a few thousandths of a second at most. That's much faster than we could manually mix the test substances that we use, and then transfer the mixture to the observation cell where the measurements are taken."

The stopped flow unit is a computer-controlled drive system that pushes a pair of syringe plungers to quickly combine two test substances -- one substance contains the proteins in an unfolded state, and the other is a buffer that allows the proteins to return to their original folded structure. As the combined substances are forced into an observation cell, a spectrophotometer measures changes in light passing through the observation cell and reveals the protein folding. The computer then collects and analyzes the data from the folding process, which can occur in less than one one-thousandth of a second.

"The idea is simple -- you bring two solutions together, and then study the properties of the resulting new solution," Mehl says. "The challenge is bringing them together very quickly, and then immediately monitoring what is happening."

Learning the Nature of Nature

Mehl and a Knox student, Sarah Kurian, of Elburn, Illinois, are currently using the device to examine GrpE1-112 -- a modified protein created during prior work by Mehl's research group. It is a variation of the GrpE protein found in E. coli bacteria. Both GrpE and GrpE1-112 are oligomeric proteins -- composed of multiple strands of amino acids. While GrpE has two amino acid chains, GrpE1-112 has four chains -- making its folded structure more complex, but also closer to other biologically important proteins.

"Most of the research on protein folding that's been done so far is on simpler monomeric proteins that have only one chain," says Kurian, whose work in Mehl's lab is part of her College Honors project in biochemistry. "In nature, most proteins are oligomeric. That makes our work more relevant to protein folding as it occurs in nature," Kurian says. "If we can learn more about the proper mechanism of folding and unfolding, we can contribute to the work that other scientists are doing, to figure out treatments for diseases, such as Alzheimer's Disease, that is caused by protein misfolding."

A biochemistry major with a minor in music, Kurian is planning to attend medical school and has already been guaranteed admission to Rush Medical College in Chicago next year, through an early admission agreement between Knox and Rush.

The GrpE1-112 mutant protein was created in earlier research that Mehl did with two Knox students -- Luke Heskett, a 2000 graduate now a physician, and Sumesh Jain, a 2003 graduate currently in medical school -- and Borries Demeler of the University of Texas Health Science Center at San Antonio. Faculty-student collaborations are a prominent feature of the experimental sciences at Knox, which is in the top 3% of colleges in the proportion of its graduates who go on to earn doctorates in the sciences.

"The stopped flow apparatus expands one of the most versatile research instruments we have in chemistry and biochemistry -- the RSM 1000 Spectrophotometer from On-Line Instrument Systems Inc.," Mehl says. Knox originally purchased the RSM 1000 with funding from the Dreyfus Foundation, for use in research by chemistry professor Lawrence Welch. A subsequent grant from the National Institutes of Health provided a circular dichroism module that extended its capabilities to Mehl's biochemistry research, and a grant from the Scripps Foundation in 2007 allowed for a full upgrade of the spectrophotometer.

"This National Science Foundation grant opens up new opportunities for faculty and undergraduate research," Mehl says. "There will be more 'mini' research projects in advanced biochemistry and chemistry courses that can extend the work that Sarah and I are doing right now." In addition to the research by student-faculty collaborations in chemistry and biochemistry, Mehl said the use of stopped flow device will be incorporated into a number of regular courses in the two programs.

Founded in 1837, Knox is a national liberal arts college in Galesburg, Illinois, with students from 47 states and 48 countries. Knox's "Old Main" is a National Historic Landmark and the only building remaining from the 1858 Lincoln-Douglas debates.