Biophysicist in Profile

 

Christine Karim

Christine Karim, Research Associate Professor in the Department of Biochemistry, Molecular Biology, and Biophysics at the University of Minnesota, has built her career by crossing things: cultural boundaries, scientific disciplines, the Atlantic Ocean, and the threshold of the University of Minnesota elevator.

“My research specifically focuses on the regulation of calcium transport in the heart, which plays a major role in current hypotheses about the causes of heart failure and possible therapeutic approaches,” Karim says. In addition to running her own peptide synthesis lab, she is part of an interdisciplinary team comprised of biochemists, spectroscopists, and physiologists, all working toward a common aim: to understand the principles of protein structural dynamics that govern muscle function and malfunction. The group is led by David Thomas, William F. Dietrich Professor of Structural Biology and Biophysics, and Fellow of the Biophysical Society. “My goal is to combine multidisciplinary approaches of chemical synthesis, biochemical reconstitution, functional assays, and magnetic resonance spectroscopy to understand and control the protein-enzyme mechanism by which the small protein phospholamban (PLB, 52 amino acids) regulates the calcium pump,” Karim says. Her current role is to synthesize PLB with the TOAC amino acid at a particular position in the protein, then incorporate the amino acid into membranes, using electron paramagnetic resonance (EPR) experiments to determine its orientation and rotational dynamics. “We have demonstrated that PLB phosphorylation induces an order-to-disorder (T-to-R) transition, and it is this dynamic structural change that regulates the Ca-ATPase,”she says. “This work laid the groundwork for the design of drugs and new PLB mutants for possible application in recombinant gene therapy for treating heart failure.”

From a young age Karim nurtured an interest in science and technology. “As a child I vividly remember how technology was progressively conquering every facet of daily life, from the TV to the refrigerator to the washing machine,” she says. Growing up in Wernigerode, a small town in former East Germany, Karim was swept up in the highly televised advances in space exploration at the time. “These early impressions played an important role in my decision to pursue a scientific career,” she says, “a decision that was anything but obvious given that none of my family members had college degrees.” After spending her high school summers working menial, uninteresting jobs, she landed one that excited her: volunteering in a lab operated by Jenapharm, a now defunct pharmaceutical company. “After that summer I knew what I wanted to be,” she says. Her summer position evolved into lab technician training with Jenapharm. She went on to earn both a bachelor’s and a master’s degree in chemistry at the Technischen Hochschule Merseburg, and a PhD in biochemistry at the University Kaiserslautern. Her PhD work on the synthesis of spin-labeled nucleotides and enzyme binding studies using EPR spectroscopy led to a postdoctoral position at the University of Bochum, where she used EPR spectroscopy to study protein dynamics, synthesizing spin label compounds for site-directed spin labeling on proteins.

In 1992, Karim’s career shifted when her husband, Naimul Karim, a Division Scientist at 3M, was transferred from Neuss, Germany, to Minneapolis, Minnesota. In an effort to establish her own career in new country, Karim joined Thomas’s group. “We have worked together constantly since that time,” says Thomas. “By far her most important contribution, to my lab and to the field of biophysics, is her pioneering application of peptide synthesis to membrane biophysics, spin label EPR, and cardiac physiology.” Today, Karim happily contributes to a field she loves for its nature. “It is a multidisciplinary field that uses cutting-edge technologies and allows me to collaborate with many investigators,” she says. “It is dedicated to the investigation of life.” These are also some of the reasons she attends the Biophysical Society Annual Meeting. “It is an excellent opportunity to meet other scientists from all over the world,” she says.

The rest of the year, though, the elevator at the University of Minnesota offers the chance to meet local collaborators. Henriette Remmer, Director of the Protein Structure Facility at the University of Michigan, met Karim in that very spot. Both German women building their scientific careers in Minnesota, they discovered that this was only the beginning of what they had in common. “Our first project was the manual solid phase synthesis of PLB, where I introduced Christine to the methodology and tricks and trades of peptide synthesis,” says Remmer. “In subsequent years Christine developed and established a new research area by integrating peptide synthesis with biochemistry and biophysics. As a scientist, Christine is extremely creative, imaginative, and shows a lot of perseverance in her research.” The elevator initially brought Ameeta Kelekar, Associate Professor at the University of Minnesota Masonic Cancer Center, and Karim together, too—as well as the talented youth math classes taught through the University of Minnesota, which both Kelekar’s and Karim’s children attended. At Kelekar’s request, Karim synthesized a Noxa protein for Kelekar’s lab, a hard-to-study pro-death protein that appeared to be modified by phosphorylation of a single residue in certain cancer cells. “The Noxa peptide that Christine synthesized allowed us to study the protein in vitro and to identify the intracellular kinase responsible for the phosphorylation,” Kelekar says. “This was a major finding in our field and one that could not have been made without Christine’s contribution.” The two periodically meet to plan future projects over lunch or coffee. “These are always relaxing times where we can talk science and also exchange news about our families,” Kelekar says.

Family has always ranked high on Karim’s priority list. “Being a mother and a wife, I have the same work-life balance issues that most women with a professional career face,” she says. She put in immense effort helping her sons Jawed and Ilias transition to American life, incorporating family activities such as hiking, cooking, and even line dancing. “The most useful things my mother has taught me, she has taught me by example: to work hard and to love life,” says Ilias, now a senior at Stanford University.

“The most rewarding aspect of my work is that it has served me internationally, even between societies where communication was impossible, like East Germany and the US,” Karim says. “I was glad to use one common language to work towards a better understanding of human health and life.” Through her research and collaborations, Karim furthers this understanding by crossing the distance between scientific disciplines. “I plan on doing my current work for a long time to come.”

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April 2012 Table of Contents