Karin Åkerfeldt

Professor of Chemistry; Department Chair

Biography

I was born in Stockholm, Sweden. My undergraduate studies in chemistry, at the University of Stockholm, had a profound influence on my later decision to pursue an academic career at an undergraduate institution. Particularly, my research experiences gained with Dr. Per Garegg (carbohydrate synthesis) and Dr. Bengt Mannervik (studies on the enzyme glutathion S-transferase) made it clear to me how important undergraduate research is in providing an exciting and fulfilling chemistry education. After I completed my B. Sc. degree, I went to the United State as a Fulbright Scholar to work on porphyrin synthesis with Dr. Kevin Smith at the University of California, Davis. I then returned to Stockholm to continue my studies, now on ribonucleotide chemistry with Dr. Per Garegg. A couple of years later I decided to go back to the US to pursue my Ph. D. degree. My interests in biochemistry and synthetic organic chemistry led me to work on a project in bioorganic chemistry in Dr. Paul Bartlett's group at the University of California, Berkeley. There I worked on the design and synthesis of multisubstrate and transition state analog inhibitors. After the completion of my Ph. D., I did postdoctoral work in the area of protein design (specifically, ion channels) in Dr. Bill DeGrado's lab at DuPont, Delaware. Since then, I worked as an Assistant Professor in Chemistry at Rutgers, the State University of New Jersey, Camden campus, for five years before I moved, in May of 1998, to the Chemistry Department at Haverford College, Pennsylvania.

Interests: the outdoors and traveling.

Education

B.S., University of Stockholm

M.S., University of California, Davis

Ph.D., University of California, Berkeley

Research

Using the background and tools of a synthetic organic chemist, I am interested in understanding how the intricate and beautiful structures of proteins relate to their function. Toward this goal, we use computer graphics modeling, organic synthesis and purification methods, solid-phase peptide synthesis, HPLC, and a variety of biophysical techniques. I have four specific areas of interest: (1) Ca2+-binding proteins of the EF-hand type, (2) porphyrin-modified peptides for light-harvesting applications, (3) peptide models of ion channel proteins, and (4) antagonists of human chorionic gonadotropin.

I collaborate with groups who have complementary skills to my own. The Ca2+-binding protein project is, for example, a collaborative effort with Dr. Sara Linse at Lund University, Sweden, who is a biophysicist and a molecular biologist. We frequently send students back and forth between our labs. We are working on several Ca2+ proteins, including calbindin D28k, a protein that protects nerve cells from programmed cell death, following conditions of Ca2+ overload, and calmodulin, a ubiquitous and highly conserved protein found in all eukayortic cells. We synthesize Ca2+-binding sequences to study them individually and in combinations, as they occur naturally, to study how they affect each other in Ca2+binding. We also modify these proteins, including incorporating chromophores for fluorescence resonance energy transfer (FRET) studies.

In a second project, we make simple peptide sequences designed to model the action of specific membrane-associated, voltage-gated ion channel proteins. One of the targets, alamethicin, is a naturally occurring channel-forming peptide, which has been studied extensively by others as a model for ion conduction. This 20-residue peptide self-associates in a lipid bilayer to form conducting pores, in the presence of an applied field. The main problem, however, is that it forms pores containing a varying number of alamethicin monomers. We covalently attach alamethicin to cyclic templates, including porphyrins, cyclodextrins and aza crown ethers, in order to freeze out one pore size and, hence, only one conductance state, which significantly simplifies subsequent data analyses.

The aim of a third project is to attach porphyrins to a peptide scaffold for the construction of nanowires capable of efficient energy and electron transfer. The structures are inspired from nature, including the antenna complexes present in plants and photosynthetic bacteria, which are responsible for light harvesting. In our system, the scaffold consists of a peptide sequence in which the architecture may be manipulated by varying the spacing and orientation of covalently attached porphyrin moieties along the peptide chain. The goal is to learn and understand the synergistic relationship between the structure of the peptide and the spacing between the porphyrins in optimizing light-induced energy transfer. This project is an interdepartmental collaboration with Walter Smith in Physics and Robert Fairman in Biology.

A fourth project is in collaboration with Dr. Patrick McIlroy, a biologist at Rutgers University, Camden. In this project we design and synthesize simple peptides as antagonists of human chorionic gonadotropin. The main incentive for this work is to learn more about the interactions between the hormone and its receptor.