Dr. Beth Abdella
Dr. Abdella is working with a team of faculty and upper level students to develop a lab program for the new three-course sequence: CH/BI 125, CH/BI 126 and CH/BI 127. This sequence is an alternative to the departmental courses: Bio 125, Chem 125 and Chem 126. Dr. Abdella teaches the first integrated course (CH/BI 125), and so has been most involved with lab development for that course. Other faculty working on this project include Jeff Schwinefus and Kim Kandl. New labs for CH/BI 125 include: Gas Evolution and Masses of Gases, Electro-Lights, Interactions of Energy and Matter, and Is the Minnesota Phosphorus Lawn Fertilizer Law Working?
Dr. Doug Beussman
Dr. Beussman's lab develops and applies bioanalytical techniques to study interesting biological questions. Students in this lab make extensive use of the new electrospray LC-MS instrument in their work, as well as various separation methods, including HPLC, affinity chromatography, and 1D- and 2D-gel electrophoresis. Most of the focus is on developing methods for the analysis of peptides and proteins.
This group is interested in developing methods to analyze large combinatorial libraries in order to identify lead drug candidates for a variety of diseases. Currently, a main focus is in identifying potential anti-angiogenesis drugs targeted against vascular endothelial growth factor receptor VEGFR2. Anti-angiogenesis drugs prevent tumors from forming their own vasculature system, thus "starving" the tumor.
Dr. Beussman's group also collaborate with labs of other Biomolecular faculty in order to identify proteins that are of interest in their research. In summer 2004, they are collaborating with Dr. Cole's lab to identify fenestrin and other proteins of interest from tetrahymena.
Dr. Eric Cole
Dr. Cole's laboratory explores the developmental biology of the freshwater ciliate, Tetrahymena thermophila. This unicellular organism undergoes both asexual reproduction (mitosis and cell division) and sexual reproduction (conjugation: meiosis, nuclear exchange & fertilization). Both of these pathways are rich in extraordinary biological activities. Ciliates also present unique opportunities to explore fundamental questions regarding both protistan and metazoan evolution. This group utilizes techniques borrowed from classical genetics, molecular genetics, protein biochemistry, and state-of-the-art microscopy. The photo, below, shows an abnormal microtubule formation in Tetrahymena.
Dr. Kim Kandl
Work in Dr. Kandl's lab focuses on using the budding yeast, Saccharomyces cerevisiae, as a model organism to study the role of the actin cytoskeleton in protein synthesis (translation). Translation is a key step in the expression of most genes. An interaction between components of the translational machinery and actin implicate the cytoskeleton in the compartmentalization of translation so that proteins are made where they are needed in the cell.
The actin cytoskeleton gives cells shape and structure, and actin is involved in a number of cellular processes including cell division and growth. More recently, evidence from the Kandl lab and others has shown that actin interacts with a number of protein factors involved in translation, and the group's genetic studies have suggested that the actin cytoskeleton plays a role in translation. This previous work demonstrated that although actin does not have a global effect on translation in yeast, actin does play a role in translation fidelity, as yeast strains with actin mutations read through stop codons. The Kandl group uses a variety of techniques from the fields of genetics, biochemistry and cell and molecular biology to test the hypothesis that the fidelity defects of actin mutants are caused by altered physical or functional interactions with translation factors known to affect translation fidelity.
Dr. Greg Muth
Dr. Muth's group is currently working on two projects, each centered around the structure and function of RNA.
1. Gene Regulation by RNA Riboswitches
Recent advances in genomics, the mapping of genes and their functions, have provided a wealth of information for researchers. One of the areas that has benefitted is the study of gene regulation, the ability of an organism to selectively turn off and on certain genes in response to environmental conditions or a specific times during its lifecycle. Of particular interest are short sequences of mRNA upstream of some genes that are sensitive to the intercellular concentration of certain metabolites. The metabolites appear to bind to and alter the structure of the mRNA. This conformational change affects the transcription and/or translation process, thus switching the gene either on or off. To better understand the details of the RNA "riboswitches," we are comparing the regulatory regions of the thiamine (vitamin B1) biosynthesis gene from E. Coli, R. Etli and B. Subtilis using a variety of biochemical and biophysical techniques.
This project utilizes interdisciplinary techniques from biochemistry, microbiology, genetics, cell biology and bioinformatics. The Muth group works jointly with members of the Schwinefus team.
2. Design and Synthesis of Conformationally Constrained RNA Oligonucleotides
Small, highly structured fragments of mRNA have been shown to play important roles in numerous biological processes. For example, specific genes can be turned off by the presence of small interfering RNA, and the presence of small RNA molecules has also been shown to disrupt the binding of the nucleocapsid protein to HIV-1 RNA or the binding of the Rex fusion protein to its target in haman T-cell leukemia virus type 1. While the sequence of these RNA fragments plays a role in their binding, the Muth group hypothesizes that the overall structural architecture of these RNA fragments is also a vital component. To address this, the Muth group is chemically synthesizing a series of RNA nucleotides with varying degrees of bend and then incorporating them into short RNA oligonucleotides. Tests will be done for the presence of unique structural attributes using nuclear magnetic resonance spectroscopy, gel-shift and various protein binding assays.
This project utilizes interdisciplinary techniques from biochemistry, physical chemistry and organic chemistry.
Dr. Janice Pellino
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Dr. Jean Porterfield
Dr. Porterfield became involved with the Biomolecular Sciences in graduate school, when she started using DNA sequences as a means for hypothesizing phylogenetic relationships among the fish species that she studied. She and her students continue to apply molecular genetics in this way, expanding their projects to include analyses at the population level. They are most recently focusing on the analysis of two kinds of data sets: DNA sequences of mitochondrial genes, and length variation of short tandem repeats in the nuclear genome (also known as microsatellites). Analysis of both data sets provides insight into the evolutionary history and current biology of Minnesota's fish species.
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Dr. Jeff Schwinefus
DNA and RNA Interaction with Small Molecules
The stability of DNA double helices and RNA folded structures is dependent not only upon hydrogen bonding, base stacking, electrostatic interactions, and hydration, but also on the interactions of organic solute molecules at specific or nonspecific nucleic acid sites. Understanding how the interaction of small molecules affects the chemical and physical properties of DNA and RNA requires knowledge about the nucleic acid structural changes induced by these small molecules.
In one case, the Schwinefus group uses electrostatically neutral organic molecules termed cosolutes (also called osmolytes) to vary water concentration (activity) and produce significant changes in the free energy of DNA or RNA melting by having favorable interactions with the newly exposed, unfolded surface areas of these nucleic acids. Accompanying such a change is structure is a concomitant decrease in the hydration of DNA and RNA.
In a second case, the Schwinefus group uses metabolites that actively bind to select regions on folded RNA structures to regulate gene expression. These RNA riboswitches generally undergo a structural change when metabolites bind. The goal is to correlate these RNA structural changes with metabolite binding to gain further insight into the riboswitch mechanism of gene regulation.
This project is a strong mix of biochemistry and physical chemistry, expecially thermodynamics and spectroscopy. Students involved in this research routinely use differential scanning calorimetry, laser light scattering, and UV-absorbance for the study of biopolymers.
Dr. Kathy Shea
Dr. Shea is interested in the evolutionary ecology of plants. She has studied population genetics and outcrossing rates in spruce and fir tree species. More recently she and students have examined the effects of habitat fragmentation and small population size on genetic variation in balsam fir (Abies balsamea). The low levels of genetic variability measured in small isolated populations on cool north-facing cliffs in MN and Iowa, suggest that these populations may require active management to survive periods of rapid climate change. Since 1990 summer students working with Dr. Shea have studied the growth and survival patterns of deciduous and conifer trees planted as part of the St. Olaf Natural Habitat Restoration Program. Measurements of tree height and diameter allow us to compare growth patterns of different species and analyze methods of restoration. Statistical models have been developed to compare actual and predicted growth patterns. Information obtained will lead to a better understanding of growth in young trees, the process of succession, and methods of forest restoration.
Dr. Anne Walter
Dr. Walter's interests in how animals cope with the challenges of the physical environment lead her and her students to study the properties of the selective barrier that separates "in" from "out" in living systems, the biological membrane. In particular her research centers around properties of biological membrane lipids, why we have so many different types of lipids and why they are distributed in very specific ways in the cell. Our specific research ranges from the lipid dependence of fusion between membranes, lipid requirements for phospholipase activity, the ways lipids arrange themselves in the plane of the membrane, the effects of hydrophobic compounds such as the plant phytoalexins on membrane properties (lipids and proteins) and reconstitution of membranes using detergents. These studies have a common thread-i.e., the very specific chemistry of each lipid in the membrane affects the critical properties of the membrane (charge, fluidity, thickness) in ways that can be assessed using thermodynamic principles. These properties, turn out to affect all sorts of biological functions from transfer of materials to which proteins are arranged at the membrane surface to enzyme activity levels.
