Biography of Tim Machonkin, Assistant Professor of Chemistry (Analytical and Inorganic)

I was born in Rochester, NY to a two-chemist family.   I attended college at the University of Michigan, where my love of transition metal-containing enzymes began.   From my sophomore year until graduation, I worked with Prof. Vincent Pecoraro, studying synthetic models of the active sites of manganese-containing enzymes and the fundamental chemistry of manganese in high oxidation states.   I graduated in 1993 with a B.S.--Chemistry (Honors) and a B.S. with a concentration in Cellular & Molecular Biology.   After a brief internship at Abbott Laboratories, I attended graduate school in Chemistry at Stanford University.   There, I worked w/ Prof. Edward Solomon on the chemistry of a copper-containing enzyme in human blood called Ceruloplasmin, as well as its yeast homolog called Fet3p.   I developed expertise in many areas of optical and magnetic resonance spectroscopy, in protein chemistry, and in air-sensitive technique.   I also developed my love of teaching:   I mentored several undergraduates in the lab, I was a freshman/sophomore academic advisor for three years, and I taught for two summers in the Stanford Summer Science & Math Institute (a program for incoming freshman predominantly from underrepresented minority groups interested in science and engineering).   After graduating in 2000, I went to the Biochemistry Department of the University of Wisconsin, where I was a National Institutes of Health postdoctoral fellow in the laboratory of Prof. John Markley.   There, I developed novel methods for obtaining nuclear magnetic resonance (NMR) spectra of proteins that contain paramagnetic transition metal ions--a type of system that is generally considered to be difficult or impossible to study by NMR.   In 2003, I returned to Rochester, NY (didn't learn that lesson the first time...) where I began my first faculty position in the Department of Biochemistry and Biophysics at the University of Rochester.   I began using a technique called "directed evolution", which is a type of high-throughput random mutagenesis that can allow one to "evolve" novel properties in proteins.   I used this technique to modify a copper-containing enzyme called Tyrosinase for improved activity towards chlorophenols, which are common pollutants in wastewater, particularly from the pulp and paper industry.   The eventual goal is to demonstrate that such a modified enzyme could be applied to remove pollutants.   At Rochester, I realized that I badly missed teaching and working with undergraduates.   So, in 2006 I joined the faculty in Chemistry at Whitman College.   Here, I am continuing to work on mutagenesis of metal-containing enzymes with possible applications in the remediation of pollutants.

In my (largely hypothetical) free time, I enjoy hiking, cycling, skiing, cooking, and listening to 20 th -century classical music.   I have also, on occasion, been known to play violin and viola.

Curriculum Vitae

Research Experience and Employment History

1991-1993:  Undergraduate research/honors thesis.   Reactivity of mononuclear dichloro-manganese(IV) Schiff base complexes towards alkenes; investigated by GC-MS and NMR.   Mentor:   Vincent L. Pecoraro.

1993, summer: Intern, Abbot Laboratories.   Synthesis of a series of antagonists of the peptide hormone endothelin.

1993-2000: Graduate research.   Spectroscopic, magnetic, electrochemical, and transient kinetic studies of two eukaryotic multicopper oxidases (ceruloplasmin, Fet3p) involved in iron metabolism.   Accomplishments:   understanding the function of the copper sites, their redox and electron transfer properties, accessibility and reactivity towards substrates, and how these relate to the enzymes' physiological function.   Mentor:   Edward I. Solomon.

2000-2003.:  Postdoctoral Research.   Paramagnetic NMR studies of human [2Fe-2S] ferredoxin.   Accomplishments:   development of novel methodology for the study of paramagnetically broadened resonances that cannot be assigned by traditional 1 H-detected 2D and 3D methods.   Mentor:   John L. Markley.

2003-2006:  Assistant Professor, University of Rochester Medical Center, Department of Biochemistry and Biophysics.   Accomplishments:   (1) Random mutagenesis of tyrosinase for improved activity towards chlorinated phenols for use in bioremediation.   Mentored   five undergraduates, three technician, and one graduate student (shared with faculty member in Chemistry).

2006-present:  Assistant Professor, Whitman College, Department of Chemistry.

Teaching, Advising, and Mentoring Experience

1993, fall:  Teaching Assistant, Stanford University, Introductory chemistry laboratory.   Taught section.

1995, spring:  Teaching Assistant, Stanford University, Undergraduate physical inorganic chemistry.   Held office hours, developed exam and review material.

1995, fall:  Head Teaching Assistant, Stanford University, General chemistry.   Taught section, held office hours, developed exam material, supervised teaching assistants, developed web-based material, orchestrated grading sessions, served as liaison between instructor, teaching assistants and students.

1994-1997:  Freshman/Sophomore Academic Advisor, Stanford University.   Advised undergraduates on courses and scheduling, academic problems and opportunities, and declaration of major.

1996, summer to 1997, summer:  Instructor, Stanford University, Intensive three-week program for incoming underrepresented-minority freshmen interested in science.   Developed curriculum (including problem sets and exam material), gave lectures, held office hours, supervised undergraduate peer leaders.

1998, spring:  Guest Lecturer, Stanford University, Graduate-level coordination chemistry.   Developed material and presented two lectures on molecular magnetism.

1997-2000:  Mentor, Stanford University.   Trained and guided two undergraduates and two first-year graduate students.

2001-2003:  Mentor, University of Wisconsin.   Trained and guided one undergraduate and two graduate student.

2003, fall; 2004, fall; 2005, fall:  Lecturer, University of Rochester, Graduate-level biochemistry.   Taught the section on biomolecular NMR, including preparation of problem set and exam materials.

2004, spring:  Lecturer, University of Rochester, Graduate-level structural biology.   Taught the section on biomolecular NMR, including preparation of problem set and exam materials and coordination of NMR spectrometer demonstration.

2004, fall:  Lecturer, University of Rochester, Graduate-level enzymology.   Taught a section on non-heme iron enzyme structure, function and mechanism.

2003-2006:  Mentor, University or Rochester.   Trained and guided six first-year rotating graduate students, five undergraduates, three technicians, and one graduate student shared with a faculty member in Chemistry.

Honors, Fellowships, and Awards

1991, 1992       Eli Lilly Undergraduate Summer Research Fellowships

1993                 Honors in Chemistry

1993                 American Institute of Chemists Award for Outstanding Senior Chemistry Major

1993                 Phi Beta Kappa

1993-1996        National Science Foundation Predoctoral Fellowship

1996-1997        Stanford University Lieberman Fellowship

1997                 Award for Outstanding Freshmen/Sophomore Academic Advisor

2000-2003        National Institutes of Health Postdoctoral Fellowship

2005-2006        NYSTAR Watson Investigator (one of 10 per year in New York)

Publications

"A Structurally Characterized Dichloro-Manganese(IV) Complex Capable of Halogenating Alkenes." Law, N.A.; Machonkin, T.E.; McGorman, J.P.; Larson, E.J.; Kampf, J.W.; Pecoraro V. L., J. Chem. Soc. Chem. Comm. 1995 , 2015.

"Multicopper Oxidases and Oxygenases." Solomon, E.I.; Sundaram, U.M.; Machonkin, T.E. Chem. Rev. 1996 , 96 , 2563.

"Spectroscopy of Multi-Copper Oxidases." Solomon, E.I.; Machonkin, T.E.; Sundaram, U.M.. in Multi-Copper Oxidases, edited by A. Messerschmidt, World Scientific Publishing Company. 1997 , 103.

"Electronic and Geometric Structure of a Trinuclear Mixed-Valence Copper (II, II, III) Cluster." Root, D.E.; Henson, M.J.; Machonkin, T.E.; Mukherjee, P.; Stack, T.D.P.; Solomon, E.I. J. Am. Chem. Soc. 1998 , 120 , 4982.

"Spectroscopic and Magnetic Studies of Human Ceruloplasmin: Identification of a Redox-Inactive Reduced Type 1 Copper Site." Machonkin, T.E.; Zhang, H.-H.; Hedman, B.; Hodgson, K.O.; Solomon, E.I. Biochemistry 1998 , 37 , 9570.

"Spectroscopic Studies of O 2 Intermediates   in Copper Proteins:   Electronic Structure Contributions to Function in Bioinorganic Chemistry." Solomon, E.I.; Palmer, A.E.; Sundaram, U.M.; Machonkin, T.   in Spectroscopic Methods in Bioinorganic Chemistry , ACS Symposium Series, edited by E.I. Solomon and K.O. Hodgson, 1998 , 423.

"Investigation of the Anomalous Spectroscopic Features of the Copper Sites in Chicken Ceruloplasmin:   Comparison to Human Ceruloplasmin." Machonkin, T.E.; Musci, G.; Zhang, H.-H.; Bonaccorsi di Patti, M.C.; Calabrese, L.; Hedman, B.; Hodgson, K.O.; Solomon, E.I. Biochemistry 1999 , 38 , 11093.

"The Thermodynamics, Kinetics, and Molecular Mechanism of Intramolecular Electron Transfer in Human Ceruloplasmin." Machonkin, T.E.; Solomon, E.I. J. Am. Chem. Soc. 2000 , 122 , 12547.

"Spectroscopy and Reactivity of the Type 1 Copper Site in Fet3p from Saccharomyces cerevisiae :   Correlation of Structure With Reactivity in the Multicopper Oxidases." Machonkin, T.E.; Quintanar, L.; Palmer, A.E.; Hassett R.; Severance S.; Kosman D.J.; Solomon E.I. J. Am. Chem. Soc. 2001 , 123 , 5507.

" 13 C{ 13 C} 2D NMR:   A Novel Strategy for the Study of Paramagnetic Proteins with Slow Electronic Relaxation Rates." Machonkin, T.E.; Westler, W.M.; Markley, J.L. J. Am. Chem. Soc. 2002 , 124 , 3204.

"Electron-Nuclear Interactions." Machonkin, T.E.; Markley, J.L. in Encyclopedia of Nuclear Magnetic Resonance , Volume 9, edited by D.M. Grant and R.K. Harris, Wiley, 2002 , 384.

"The EPR Spectrum of a Cu(II/II/III) Cluster:   Anisotropic Exchange in a Bent Cu(II) 2 O 2 Core." Machonkin, T.E.; Mukherjee, P.; Henson, M.J.; Stack, T.D.P.; Solomon, E.I. Inorg. Chim. Acta , 2002 , 341 , 39.

"Correlation Between Hydrogen Bond Lengths and Reduction Potentials in Clostridium pasteurianum Rubredoxin." I-Jin Lin, I.-J.; Gebel, E.B.; Machonkin, T.E.; Westler, W.M.; Markley, J.L. J. Am. Chem. Soc. , 2003 , 125 , 1464.

"Strategy for the Study of Paramagnetic Proteins with Slow Electronic Relaxation Rates:   Application to Oxidized Human [2Fe-2S] Ferredoxin" Machonkin, T.E.; Westler, W.M.; Markley, J.L., J. Am. Chem. Soc. , 2004 , 126 , 1464.

"Paramagnetic NMR Spectroscopy and Density Functional Calculations in Analysis of the Geometric and Electronic Structures of Iron-Sulfur Proteins" Machonkin, T.E.; Westler, W.M.; Markley, J.L., Inorg. Chem. 2005 , 44 , 779.

"Changes in Hydrogen Bond Strengths Explain Changes in the Reduction Potentials of a Series of Ten Rubredoxin Variants"   Lin, I.-J.; Gebel, E.B.; Machonkin, T.E.; Westler, W.M.; Markley, J.L., Proc. Natl. Acad. Sci. U.S.A. , 2005 , in press.

"Development of a High-Yield E. coli Expression System for Streptomyces glaucescens Tyrosinase" Machonkin, T.E.; O'Mara, B.M.; Weiss, T.L.; manuscript in preparation.

Recent Talks and Poster Presentations

"The Role of the Additional Type-1 Copper Sites in Human Ceruloplasmin:   Thermodynamics and Kinetics of Intramolecular Electron Transfer." Chemistry Department Inorganic Seminar, University of Wisconsin, Madison, 2000 (talk).

"NMR Studies of Human Ferredoxin." International Conference on Bioinorganic Chemistry, Florence, 2001 (poster).

"Development of a New Strategy for the Study of Paramagnetic Proteins by NMR:   Application to Human Ferredoxin."   Experimental NMR Conference, Pacific Grove, CA, 2002 (poster).

"Development of a New Strategy for the Study of Paramagnetic Proteins by NMR:   Application to Human Ferredoxin."   International Conference on Magnetic Resonance in Biological Systems, Toronto, Canada 2002 (poster).

"Development of a New Strategy for the Study of Paramagnetic Proteins by NMR:   Application to Human Ferredoxin."   Metals in Biology Gordon Research Conference, Ventura, CA 2002 (poster).

"Structural Determinants of Electronic Structural Differences Among Classes of [2Fe-2S] Ferredoxins:   Insights from Paramagnetic NMR and Electronic Structure Calculations." International Conference on Bioinorganic Chemistry, Cairns, Australia 2003 (poster).

"Re-engineering Tyrosinase for Use in Bioremediation." Biochemistry, Cellular and Molecular Biology Graduate Cluster Retreat, University of Rochester, NY, 2005, (talk).

"Re-engineering Tyrosinase for Use in Bioremediation." Biophysics and Structural Biology Graduate Cluster Retreat, University of Rochester, NY, 2005, (talk).

"Re-engineering Tyrosinase by Random Mutagenesis for Improved Activity Towards Non-native Substrates." International Conference on Bioinorganic Chemistry, Ann Arbor, MI 2005 (poster).

Previous Extramural Research Support

NYSTAR Watson Investigator, Sept. 2005 - Aug. 2007

"Re-engineering the Enzyme Tyrosinase for Bioremediation of Toxic Phenols"

$200,000 over 2 years (ended early due to position change).

Current Extramural Research Support

Petroleum Research Fund "G"-Grant, "Understanding the Origin of Suicide Inactivation in the Extradiol Dioxygenases", $35,000 over 2 years.