Parker de Waal ’13 had a wish: he wanted to work on a computational chemistry project.
Laura Furge, the Roger F. and Harriet G. Varney Professor of Chemistry, had a challenge: she needed models of the variants of an important human enzyme. (Some background: The aforementioned enzyme, found in the liver, helps the body process medicines, but it’s not exactly the same–hence, variants–in all individuals. Such variability means some people react differently (including adversely) to important medicines. That’s a serious health problem, and part of Furge’s current grant from the National Institutes of Health calls for the study of these variants. And for such study a model of the variants’ structures would certainly be useful!)
In spring 2013, wish met challenge, and, one year later, the two researchers (along with co-author Kyle Sunden ’16) have published a paper in PLoS ONE, the online journal of the Public Library of Science.
That culminating publication traces back to a laboratory question: Could de Waal (a student in Furge’s “Advanced Biochemistry” class) make computational models of the variants? “I suggested some different ways to approach the problem,” says Furge, “and those approaches took Parker all of about two days!” It was at that point that de Waal suggested to Furge some different, more powerful computational approaches–specifically, molecular dynamics using more sophisticated software. “I said, ’Let’s go for it!’” says Furge. “And we both started on the journey to learn more about Molecular Dynamics approaches.”
The journey included consulting with other scientists around the country and the world (Germany, the Czech Republic) both by email and in person at various scientific conferences. Furge and de Waal used a supercomputer at the University of Texas for the computational work. Analysis of the resulting structures was completed by Furge and Sunden during the winter and spring terms of 2014. “The project is a beautiful example of how research and teaching go together at K,” says Furge. The work has been presented at two major medical meetings.
The paper includes 21 figures and tables. Parker de Waal performed all the experiments that led to the figures; Sunden did the experiments and analyses for two of the figures. Furge did the majority of the analysis. In true liberal arts fashion, the cross-disciplinary work combines computer science and biochemistry. Furge taught Sunden, a chemistry and computer science double major, the relevant biochemistry as they progressed with the project. Sunden hopes to continue the work for his Senior Individualized Project after he returns from study abroad in Australia. The work may one day contribute to personalized solutions for people who have adverse drug reactions to important medicines. The paper has had more than 300 views in the six weeks since it’s been published.
Great academics, cross-disciplinary collaboration, research at the edge, and science that matters! Science education at Kalamazoo College: a double helix of challenge and imagination.
Medicinal researchers and members of the Furge Lab (l-r): Rina Fujiwara, Erran Briggs, Amanda Bolles, and Laura Furge
Laura Furge, the Roger F. and Harriet G. Varney Professor of Chemistry at Kalamazoo College, is the senior and corresponding author of an important scientific paper that includes three Kalamazoo College student co-authors: Amanda Bolles ’14, Rina Fujiwara ’15, and Erran Briggs ’14. The paper is titled “Mechanism-based Inactivation of Human Cytochrome P450 3A4 by Two Piperazine-containing Compounds” and appears in Drug Metabolism and Disposition, a highly regarded, high impact international journal published by the American Society for Pharmacology and Experimental Therapeutics. The research the paper describes, which was conducted in the Furge Lab on K’s campus, contributes the understanding of how some drugs “apply the brakes to” the activity of an enzyme–in this particular case, an enzyme important to the metabolism (or processing) of about half of all medicines! What are the human implications of the work? “Many individuals take multiple medicines each day,” said Furge. “Multiple-drug regimens can lead to unwanted side effects, including drug-induced inhibition of the very enzymes responsible for the metabolism and clearance of other co-administered drugs.” In fact, side effects from drug interactions of polypharmacy therapy are the number one cause of hospitalization in the U.S. “This paper adds in understanding of how certain classes of drugs may cause this type of unfavorable medical event,” said Furge. “New insights will hopefully lead to better prevention in the future.”
The paper includes 13 figures and tables. Furge noted that Bolles, Fujiwara, and Briggs performed all the experiments that lead to those figures, and “all the work was done on the campus at Kalamazoo College. We had all the equipment here needed to complete these studies, and we have already started full swing on another set of experiments for a future publication.” The students have presented parts of the preliminary data at national meetings in the past year, and the research forms of basis of the Senior Individualized Projects for Bolles and Fujiwara.
Such research, and the extraordinary educational opportunities it provides for K students, requires the cooperation, coordination, and collaboration of many funding sources. “This is so important,” Furge stressed. The Richard Cook Fellowship and the Alan and Elaine Hutchcroft Fund (endowments created and supported by alumni gifts) paid for the summer stipends of Fujiwara and Bolles, respectively. The mass spectrometer essential to the experiments was paid for in part by the Hutchcroft Fund and a grant from the Howard Hughes Medical Institute. The research also was funded by grants Furge secured from the National Institutes of Health.
“Drug Metabolism and Disposition is an international journal with a high impact factor,” added Furge. Impact factors measure how frequently manuscripts in a journal are referenced by other authors.
K student researcher/presenters at the 2014 Experimental Biology Meeting included (l-r): Amanda Bolles, Rina Fujiwara, and Virginia Greenberger. Not pictured is Michael Korn.
Four Kalamazoo College students attended at the 2014 Experimental Biology Meeting: Amanda Bolles ’14, Chemistry; Rina Fujiwara ’15, Chemistry; Virginia Greenberger ’14, Chemistry; and Michael Korn ’14, Biology. Experimental Biology is a joint meeting of six different societies including the American Association for Biochemistry and Molecular Biology (ASBMB) as well as societies for physiology, nutrition, pharmacology, pathology, and anatomy. The meeting provides a great opportunity for students to present their work and attend a variety of engaging scientific talks. More than 15,000 scientists attended the event in San Diego, Calif.
Bolles and Fujiwara presented their research findings during the Undergraduate Poster Competition and during the regular scientific session for ASBMB. Their research involves recent work completed in the laboratory of Professor of Chemistry Laura Furge. That work has shown that two different (but related) compounds inactivate P450 3A4, an enzyme in the liver and intestine that metabolizes (or processes) a major pharmaceutical drug. The titles of the Bolles and Fujiwara posters were, respectively, “5-Fluoro-2-[4-[(2-phenyl-1H-imidazol-5-yl)methyl]-1 piperazinyl]pyrimidine is a mechanism based inactivator of CYP3A4” and “Mechanism-based inactivation of human CYP3A4 by a piperazine-containing compound.” The ASBMB competition includes posters of some 300 students from a variety of college and universities across the country. One grand prize award was presented to a student in each of four research categories (bioenergetics/protein structure, cell biology/developmental biology, DNA/gene regulation, and immunology/microbiology/neurobiology). Bolles won the $500 grand prize in the bioenergetics/protein structure category and was recognized the next day before an audience of hundreds of scientists, educators, and students at the award lecture for outstanding contributions to education. Bolles’s presentation derived from her Senior Individualized Project (SIP), which will be published later this year along with results from co-author Fujiwara.
Greenberger conducted her SIP research in the laboratory of Professor of Chemistry Regina Stevens-Truss. The abstract she presented at the meeting was titled “Bacterial Action of Novel Cationic Peptide Sequences.” As more antibiotic resistance is observed in patients, new sources of antibiotics are being investigated, including short peptide sequences. Greenberger’s work in the Truss lab was aimed at determining the antibiotic activity (and the precise mechanisms of action that yielded the activity) of two newly studied peptide sequences.
Dr. Furge also presented a poster in the ASBMB regular scientific session based on work started last year by Parker de Waal ’13. The work began as part of a course assignment in Furge’s “Advanced Biochemistry” course and grew into an elegant computational study of structural differences between select variants of the drug-metabolizing enzyme P450 2D6. de Waal used molecular dynamics methods to show how subtle differences in the enzyme structure can help explain differences in the metabolizing abilities of the enzymes. The study is being completed by Kyle Sunden ’16. While in San Diego, Furge spent an afternoon at the Skaggs School of Pharmacy at the University of California-San Diego discussing the implications and approach of the study with other scientists in this field.
Korn attended the American Physiological Society (APS) portion of the Experimental Biology meeting. He presented the results of his SIP work (conducted in the laboratory of Dr. Christopher Mendias at the University of Michigan) in the APS Student Poster Competition. Korn’s abstract received the David Bruce Outstanding Undergraduate Abstract Award. The title of his presentation was “Simvastatin reduces myosteatosis following chronic skeletal muscle injury.”
The future is promising for all four of these outstanding student researchers. In the fall, Bolles will enter the University of Michigan Graduate Program in Biomedical Sciences; Greenberger will matriculate to the chemistry department at Pennsylvania State University to begin work on her Ph.D; Korn will attend the University of Michigan Medical School; and Fujiwara will complete her SIP with Furge this summer. She plans to attend graduate school after her June 2015 graduation from K.
Professors Furge and Truss are both members of the ASBMB and attend the annual meeting each year. Truss also directs a National Science Foundation (NSF)-funded workshop for area high school science teachers in connection with the annual ASBMB meeting. This year’s workshop attracted more than a dozen local teachers who learned science and teaching strategies to use in their classrooms. Attendees at the workshop are also eligible for mini-grants to support further development of their teaching after the workshop. A recent article describes the impact of this workshop (which is in its fourth year).
In other meeting news, the Ruth Kirschstein Diversity in Science Award was given jointly to President Freeman Hrabowski III and Professor Michael Summers of University of Maryland-Baltimore County. Professor Summers was the SIP mentor to Erran Briggs ’14 and has worked closely with Professor Truss on the Professional Development and Minority Affairs Committees of ASBMB. Professor Summers also visited K’s campus in 2010 as a Howard Hughes Medical Institute Guest Scholar Lecturer. Given the connections, and important work of Summers and Hrabowski, Professor Truss arranged for Bolles, Fujiwara, and Greenberger to interview Summers for Kalamazoo College’s Arcus Center for Social Justice Leadership’s Praxis Center. Following the interview, Summers treated the students and Truss to lunch overlooking the San Diego Harbor marina! Notes from the interview will be posted on the Praxis website.
Travel to ASBMB for Bolles, Fujiwara, and Greenberger was supported by grants from the Provost Office, the Heyl Foundation (Greenberger), and the ACSJL. Korn’s travel to the meeting was sponsored by grant funds from his SIP advisor and the University of Michigan. Furge and Truss were supported by the Hutchcroft Endowment as well as their NIH and NSF grants, respectively. Next year’s Experimental Biology Meeting will occur in Boston, Mass.
Some recent news about Kalamazoo College professors:
PUBLICATIONS and EXHIBITS
Carol Anderson (Religion) published “The Possibility of a Postcolonial Buddhist Ethic of Wealth,” an article in Buddhist-Christian Studies…Rose Bundy (Japanese Language and Literature) published “Beneath the Moss,” a set of translations by Fujiwara Shunzei, in the new translation journal Transference…Henry Cohen (Romance Languages) published “The Eldorado Episodes of Voltaire’s Candide as an Intertext of Augusto Roa Bastos’ Yo El Supremo: A Utopia/Dystopia Relationship” in Revista De Estudios Hispanicos…Kiran Cunningham ’83 (Anthropology and Sociology) published “Structured Reflection for Transforming Learning: Linking Home and Away,” in the Salzburg Global Seminar’s Creating Sites of Global Citizenship…Péter Érdi (Luce Professor of Complex Systems Studies) co-authored three papers: “The Past, Present, and Future of Cybernetics and Systems Research” in the journal Systems; “An Integrated Theory of Budgetary Politics and Some Empirical Tests: The U.S. National Budget, 1791-2010” in the American Journal of Political Science; and “Anxiolytic Drugs and Altered Hippocampal Theta Rhythms: The Quantitative Systems Pharmacological Approach” in Network: Computation in Neural Systems…Jim Langeland ’86 (Biology) and Blaine Moore (Biology) are co-authors of a paper accepted for publication in Molecular Biology and Evolution that contributes to the understanding of Alzheimer’s disease. The project was partially funded by a GLCA New Directions Initiative and had four Kalamazoo College students or alumni as co-authors (see a recent K News & Events article about this here.)…Amy Lane (Anthropology and Sociology) published “Religion is not a Monolith: Religious Experience at a Midwestern Liberal Arts College,” an article in Journal of College and Character…Sarah Lindley (Art) exhibited her sculptures in shows at Eastern Michigan University, Alma College, and Hope College…Bruce Mills (English) published An Archaeology of Yearning, a book by the Etruscan Press…Siu-Lan Tan (Psychology) co-authored three chapters and served as primary editor for the book, The Psychology of Music in Multimedia (Oxford University Press, 2013).
AWARDS and GRANTS
Kiran Cunningham ’83 (Anthropology and Sociology) has been awarded the 2014 Dr. Winthrop S. and Lois A. Hudson Award, awarded biannually for the purpose of honoring outstanding K faculty members…John Fink (Mathematics) has been awarded the Lucasse Lectureship for Outstanding Teaching at K…Alison Geist (Mary Jane Underwood Stryker Institute for Civic Engagement) was awarded one of the first Kalamazoo County Spirit of Health Equity awards…Binney Girdler (Biology and Environmental Studies) has been awarded grants from the Michigan Botanical Foundation and from the Central Michigan University Institute for Great Lakes Research…Bruce Mills (English) has been awarded a GLCA New Directions Initiative grant for his work on building a civil rights oral history archive…Lanny Potts (Theatre Arts) was awarded the 2013 Wilde Award for “Best Lighting Designer of the Year” in the state of Michigan for his work on “The Light in the Piazza” at Farmer’s Alley Theatre…Regina Stevens-Truss (Chemistry) has received funding from the GLCA Expanding Collaboration Initiative to study digital resources for learning experimental science.
NEW POSITIONS
Alyce Brady (Mathematics and Computer Science) is an Arcus Center Faculty Fellow. She will work collaboratively with universities in Sierra Leone to develop sustainable open-source academic record-keeping software…Reid Gómez is Mellon Visiting Assistant Professor of Ethnic Studies, focusing on campus climate, faculty development, and curriculum development…Starting July 1, 2014, Mike Sosulski (German and Media Studies) will serve as Associate Provost and Paul Sotherland (Biology) will be the inaugural Coordinator of Teaching, Learning, and Educational Effectiveness.
ENDOWED CHAIRS
The following Kalamazoo College faculty members are the recipients of newly endowed chairs: R. Amy Elman, William Weber Professor in Social Science…Laura Lowe Furge, Roger F. and Harriet G. Varney Professor of Chemistry…Gary S. Gregg, Ann V. and Donald R. Parfet Distinguished Professor of Psychology…Ahmed M. Hussen, Edward and Virginia Van Dalson Professor of Economics and Business…Richard Koenig, Genevieve U. Gilmore Professor of Art…Amy MacMillan, L. Lee Stryker Assistant Professor of Business Management…Ed Menta, James B. Stone College Professor of Theatre Arts…Taylor G. Petrey, Lucinda Hinsdale Stone Assistant Professor of Religion.
Regina Stevens-Truss, the Kurt D. Kaufman Associate Professor of Chemistry has written an article updating an idea of hers and the American Society of Biochemistry and Molecular Biology: the HOPES Initiative. HOPES pairs teachers with working scientists so that together they could provide hands-on opportunities to students. “We didn’t anticipate the sweeping impact the program would have across the nation,” wrote Stevens-Truss in the update. The HOPES initiative has resulted in 27 partnerships in 22 cities across the U.S. and has affected the education of more than 3,600 fourth- through 12th-graders.
Three Kalamazoo College seniors presented their Senior Individualized Project (SIP) research at the Midwest Symposium on Undergraduate Research. The event took place at Michigan State University on Saturday, October 5. The students, their presentation titles, and where they did their SIP:
Sara Adelman’s poster (see photo) won the Outstanding Poster Award for Biochemistry. It was titled “Effects of Copper Bipyridine Catalysed Alkaline Hydrogen Peroxide Pretreatment on Lignocellulostic Biomass in the Ethanol Production Process.” Adelman did her research with Professor Eric Hegg ’91 at Michigan State University.
Geneci Marroquin presented a poster titled “Reactions of Cobalt(II) and Nickel(II) Complexes Containing Binucleating Macrocyclic and Pyridine Ligands with Carboxylic Acids: Formation of Binuclear Co(II), Co(II)Co(III), and Ni(II) and Tetranuclear Co(II) and Ni(II) Complexes.” Her research was done in the laboratory of Professor Thomas J. Smith at Kalamazoo College.
Kendrith Rowland conducted his research in the laboratory of Professor Catherine Murphy at the University of Illinois at Urbana-Champaign. Rowland’s poster was titled “High Sensitivity Surface Enhanced Raman Spectroscopy (SERS) Nanoplatform Based on Gold Nanoparticle Aggregates.”
Kalamazoo College Professor of Chemistry Jeffrey Bartz gave an invited talk at the symposium. That talk, “Detecting Cartwheels and Propellers by Velocity-Mapped Ion Imaging,” highlighted the SIP work of Ryan Kieda ’09, Masroor Hossain ’12, and Nic West ’12, as well as the research of Amber Peden ’11, Aidan Klobuchar ’12, Kelly Usakoski ’14, Braeden Rodriguez ’16, and Myles Truss ’17.
Three student scientists/athletes transitioned from the laboratory to the gridiron on August 16, the first day for Hornet football practice. Jake Lenning ’15 (chemistry major, health studies concentration), Joe Widmer ’14 (chemistry major, biochemistry concentration), and Jake Hillenberg ’14 (chemistry and psychology major, neurosciences concentration) spent the summer doing chemistry research–Lenning in the lab of Professor of Chemistry Greg Slough; Widmer and Hillenberg in the lab of Associate Professor of Chemistry Jennifer Furchak. Lenning’s research involves testing for differences in two variations of a resin known as the Wang Resin. Widmer and Hillenberg were working outside the laboratory on the day I visited. Lenning plays wide receiver for the Hornets, Widmer and Hillenberg are defensive linemen. The 2013 season will be the team’s second on the new Angell Field, and Lenning is excited. “We had a good season last year,” he said, “and that success will be a good foundation to build a great season this year.”
Lori-Ann Williams, Geneci Marroquin and Josh Abbott in the lab.
It’s summertime at K; the weather is hot, and so is the chemistry on the second floor of the Dow Science Center. In the first of a series of articles, we focus on chemistry research underway on campus during summer 2013.
Three students are advancing ongoing research projects in the inorganic chemistry laboratory of Professor of Chemistry Tom Smith. Each project is focused on elements included in a group known as transitional metals. Josh Abbott ’13, Lori-Ann Williams ’14, and Geneci Marroquin ’14 apply various techniques to characterize reactions that occur in nature (as well as some chemistry that nature doesn’t do) involving the elements vanadium (Abbott), manganese (Williams), and cobalt and nickel (Marroquin).
The researchers are working to create small molecule models that are motivated by the chemical reactions that occur in nature and involve more complex substances such as enzymes. All three are performing the intricate chemical experiments required to make crystal samples of molecules that result from the aforementioned reactions—enough samples, and of sufficient quality, for the technique known as x-ray crystallography, which will render a three-dimensional portrait of the molecule. (The notion of portraiture is particularly apt for the chemistry of transitional metals, known for their colors and alterations of color as a result of molecular changes.) The x-ray crystallography work will mean an August trip to Purdue University (the workplace of a long-time collaborator with Smith in these scientific projects) for Smith and the student researchers.
The work of Williams and Marroquin will form the basis of their respective Senior Individualized Projects. Williams’ work, says Smith, is more biologically oriented, and seeks to reconcile data on manganese compounds from Williams and the Smith lab with data published on manganese work from a laboratory in India. Marroquin’s is more “catalytically oriented, doing something nature doesn’t do,” she says. If Marroquin’s contribution to the ongoing project is successful, subsequent work may one day lead to more efficient energy generation. “We’re trying to save the world in this lab,” smiles Marroquin.
Abbott graduated in June but wanted to more research work in inorganic chemistry, the most liberal arts-ish of all chemistry disciplines. “It relates to all other branches of chemistry and science and is very useful for better understanding of peer-reviewed literature in biochemistry,” he said. His vanadium research originates from the way sea algae synthesize special organic molecules for self protection.
It’s been a good summer in Smith’s lab. All five of his researchers are “highly motivated and getting a lot done,” Smith said. (Leland O’Connor ’14 and Mojtaba Ahkavandafi ’15 were not in the lab the day we dropped in, and they are working on projects very different from those of the other students.)
Six students presented research work at the annual ASBMB meeting. From left: Josh Abbott, Erran Briggs, Amanda Bolles, Mara Livezey, Michael Hicks, and Nic Sweda. Hicks is a biology major; the other five are majoring in chemistry.
Six Kalamazoo College students joined two of their chemistry professors and mentors (Regina Stevens-Truss and Laura Lowe Furge) at the American Society for Biochemistry and Molecular Biology National Meeting in Boston, Mass. The students–Nicholas Sweda ’13, Mara Livezey ’13, Michael Hicks ’13, Josh Abbott ’13, Amanda Bolles ’14, and Erran Briggs ’14–presented results of their summer and academic year research experiences (Senior Individualized Projects in the cases of Nick and Josh). Nearly 300 posters from colleges across the country were part of the 17th Annual Undergraduate Student Research Poster Competition and Professional Development Workshop. Professor Furge was a judge in the competition.
The lab of Professor Paul Hollenberg at the University of Michigan was the site of Abbott’s SIP research on the role of CYP2B6 metabolism of the chemotherapeutic drug cyclophosphamide. The other five posters were based on research done at Kalamazoo College. Sweda presented ongoing studies from Professor Stevens-Truss’s lab on suramin selective inhibition of nitric oxide synthases. This work is the basis of a manuscript in preparation with Sweda and Alyssa McNamara ’11 as co-authors. Livezey, Hicks, Bolles, and Briggs each presented individual posters with results of three projects from Professor Furge’s lab on the interactions of inhibitors with human cytochrome P450 enzymes. The work presented by Bolles and Briggs is currently being prepared in a manuscript for publication with both students as co-authors along with Livezey. The posters presented by Hicks and Livezey are the basis of current NIH-funded studies in the Furge lab. In addition to the poster sessions, students attended talks, award lectures, and exhibits. Students also met with graduate school recruiters.
During the meeting, Professor Stevens-Truss directed her third annual teaching workshop for middle school and high school science teachers in the Boston area. The workshop attracted more than 70 teacher-participants from the Boston area, a record number for these ASBMB associated events. Professor Stevens-Truss’s efforts in structuring the workshops have provided a new platform for scientists to collaborate and mentor the nation’s secondary school science teachers. Scientists from across the country helped make the workshop a meaningful experience for school teachers. It was funded by a National Science Foundation grant to Stevens-Truss. Next year’s meeting will be in San Diego, Calif., and K expects to be there.
Professor of Chemistry Laura Furge has received a renewal of her National Institutes of Health (NIH) grant to support continued research in the area of drug-drug interactions. She will conduct this research with undergraduate science students at Kalamazoo College. Adverse drug-drug interactions are common among individuals who take multiple drugs (both over the counter and prescribed), particularly among older persons and among individuals whose bodies express variants of drug metabolizing (drug processing) enzymes. The research in the Furge lab will benefit human health by adding to the understanding of how certain classes of drugs may interact in individuals and cause drug-drug induced unfavorable medical events. Furge currently has five research students working in her lab and has mentored two dozen in her lab and many more in her classes over the past 13 years at K. Funding from the NIH will help ensure continued research opportunities for future generations of scientists. The grant will provide $225,000 over three years.
