EDUCATION (top)

October 2006 – May 2008

University of Sydney, Sydney, NSW AU.
Postdoctoral Fellow in X-Ray Crystallography. 
Advised by Professor J. Mitchell Guss, PhD.

September 2001 – September 2006

California Institute of Technology, Pasadena, CA USA.               
PhD in Chemistry and Chemical Engineering
Advised by Professor Harry B. Gray, PhD.
Awards:  Dow Travel Fellowship. Outstanding Graduate Teaching Assistant Service 2006 Award

August 1997 - June 2001

Sweet Briar College, Sweet Briar, VA USA.  
Bachelor of Science in Chemistry 
Advised by Professor Robert M. Granger, PhD  
Major:  Chemistry    Minor:   Studio Arts 
Honors:  Phi Beta Kappa.  Alpha Lamda Delta.  Sweet Briar Honors Scholar.  First Year National Chemistry
Award: Who’s Who Among Students in American Universities and Colleges.  Anne Gary Pannell Scholar. High Honors in Studio Arts.

 

CURRENT RESEARCH (top)

September 2008 – present

Sweet Briar College, Sweet Briar, VA USA.  

Integral membrane proteins (IMPs) perform many critical functions, such as transport, metabolism, signaling, photosynthesis, and respiration; however, little is known of their  structures.(1)  Presently, the Protein Data Bank contains a total of ~100 structures of IMPs, which is about equal to the number of solved soluble protein structures per week. (1-3)  Crystallizing IMPs is significantly more difficult, because membrane protein needs to be isolated and purified in a soluble native state, which requires a host membrane lipid and an excess of detergents (or amphiphiles) that form micelles above their critical micellar concentration (CMC). (4)  These amphiphiles need to adsorb onto the hydrophobic patches of the protein, solubilize the protein in its native fold for long enough to form high-quality crystals, and contribute to the crystalline lattice stability in order to obtain high resolution crystals. 

Composition and structure in concert with response to temperature and pressure of the amphiphile will determine its performance and function during crystallization.  The variation in size and shape of the nonpolar and polar groups of amphiphiles strongly influences self association in solution (micelles or bilayers), formation of liquid crystals (perpendicular/smectic or parallel/nematic layers)(5), and interactions with the host lipid bilayers. (6)  The challenge is to understand the connection between form and function in order to rationally design an amphiphile that would give well defined mesophases, microstructures, and manageable phase behaviors.  There have been reports on unusually shaped amphiphile, such as rigid tripods, (7) molecular umbrellas, (8) block copolymers, (9) reverse micelles, (10) and gemini surfactants. (11)  Bowl-like or pyramidic detergents can self organize into discotic nematic and/or columnar liquid crystals. (12)  Some of these pyramidic molecules have a rigid cyclotriveratrylene (CVT) core and alkyl chains extending from the rim (13-16) but no functionality along their feet (Figure 1B).  Cavitands (Figure 1A) have similar structures as CVTs with the addition of a benzene ring and full functionalization on both its rim and feet creating a quadracycle amphiphile. 

Figure 1.  Structures of (a) cavitands, (b) CVTs, and (c) proposed tricycle amiphiphile (TCA).

Functionality of cavitands allows them to be applied to an array of creative research such as scaffolds for de novo protein design, (17,18) carceplexes (19,20) or cages (21,22) for inorganic/organic reactions, and coatings for microfluidic devices. (23) However, there have been no reports on protein crystallization applications.

A novel tricycle core amphiphile (TCA) (Figure 1C) is proposed here that has structural similarities to the CVT three ring complex, but with the functionality of cavitands to serve as amphiphiles for crystallization of IMPs.  Unlike most detergents containing one or two alkyl tails, TCA can be functionalized with three alkyl chains making the molecule more rod-like, which can form thermotropic (temperature induced) smectic liquid crystalline phases aiding in crystallization of membrane proteins at lower temperatures. (16,24)  The wedge-shaped tricycle core will encourage membrane lipid bilayer insertion for reconstitution of IMPs during crystallization.  The pyramidic shaped TCA can form compact stacking of monomers that will contribute to lyotropic (water induced) mesophase formations.  The full functionality of the proposed amphiphile will contribute to the ease of structural manipulation in a way that can impact phase behavior.  Most detergents used for IMP crystallization have flexible polar heads and floppy alkyl chains that result in disordered crystal structures. 

TCA is predicted to form more structured micelles with compact head groups that can efficiently and orderly adsorb onto the protein hydrophobic surfaces.  The rigid core will aid in crystal packing by p-stacking and hydrogen bonding.  When mixed with monoolein lipid cubic phase, TCA is expected to enhance the membrane curvature, increase the bilayer elasticity, and stabilize the cubic phase for crystallization at lower temperature.   

 

References

(1)        Werten, P. J. L.; Remigy, H. W.; de Groot, B. L.; Fotiadis, D.; Philippsen, A.; Stahlberg, H.; Grubmuller, H.; Engel, A. Febs Lett 2002, 529, 65-72.
(2)        Caffrey, M. J Struct Biol 2003, 142, 108-132.
(3)        Hunte, C.; Michel, H. Curr Opin Struc Biol 2002, 12, 503-508.
(4)        Ostermeier, C.; Michel, H. Curr Opin Struc Biol 1997, 7, 697-701.
(5)        Burnell, E. E.; de Lange, C. A. Chem Rev 1998, 98, 2359-2387.
(6)        Naka, K.; Sadownik, A.; Regen, S. L. J Am Chem Soc 1993, 115, 2278-2286.
(7)        McQuade, D. T.; Quinn, M. A.; Yu, S. M.; Polans, A. S.; Krebs, M. P.; Gellman, S. H. Angew Chem Int Edit 2000, 39, 758-+.
(8)        Janout, V.; Lanier, M.; Regen, S. L. J Am Chem Soc 1997, 119, 640-647.
(9)        Kolbel, M.; Beyersdorff, T.; Sletvold, I.; Tschierske, C.; Kain, J.; Diele, S. Angew Chem Int Edit 1999, 38, 1077-1080.
(10)      Sidorov, V.; Douglas, T.; Dzekunov, S. M.; Abdallah, D.; Ghebremariam, B.; Roepe, P. D.; Matile, S. Chem Commun 1999, 1429-1430.
(11)      Menger, F. M.; Littau, C. A. J Am Chem Soc 1993, 115, 10083-10090.
(12)      Percec, V.; Imam, M. R.; Bera, T. K.; Balagurusamy, V. S. K.; Peterca, M.; Heiney, P. A. Angew Chem Int Edit 2005, 44, 4739-4745.
(13)      Elabed, A.; Daillant, J.; Peretti, P. Langmuir 1993, 9, 3111-3114.
(14)      Zimmermann, H.; Bader, V.; Poupko, R.; Wachtel, E. J.; Luz, Z. J Am Chem Soc 2002, 124, 15286-15301.
(15)      Budig, H.; Lunkwitz, R.; Paschke, R.; Tschierske, C.; Nutz, U.; Diele, S.; Pelzl, G. J Mater Chem 1996, 6, 1283-1289.
(16)      Budig, H.; Diele, S.; Goring, P.; Paschke, R.; Sauer, C.; Tschierske, C. J Chem Soc Perk T 2 1995, 767-775.
(17)      Gibb, B. C.; Mezo, A. R.; Causton, A. S.; Fraser, J. R.; Tsai, F. C. S.; Sherman, J. C. Tetrahedron 1995, 51, 8719-8732.
(18)      Mezo, A. R.; Sherman, J. C. J Am Chem Soc 1999, 121, 8983-8994.
(19)      Cotton, F. A.; Lei, P.; Lin, C.; Murillo, C. A.; Wang, X. P.; Yu, S. Y.; Zhang, Z. X. J Am Chem Soc 2004, 126, 1518-1525.
(20)      Makeiff, D. A.; Sherman, J. C. J Am Chem Soc 2005, 127, 12363-12367.
(21)      Hooley, R. J.; Van Anda, H. J.; Rebek, J. J Am Chem Soc 2006, 128, 3894-3895.
(22)      Pirondini, L.; Bertolini, F.; Cantadori, B.; Ugozzoli, F.; Massera, C.; Dalcanale, E. P Natl Acad Sci USA 2002, 99, 4911-4915.
(23)      Ichimura, K.; Oh, S. K.; Nakagawa, M. Science 2000, 288, 1624-1626.
(24)      Destrade, C.; Foucher, P.; Gasparoux, H.; Tinh, N. H.; Levelut, A. M.; Malthete, J. Mol Cryst Liq Cryst 1984, 106, 121-146.

 

PAST RESEARCH

October 2006 – May 2008   (top)

University of Sydney, Sydney, NSW AU. 

DNA cloning and manipulation of mammalian vascular adhesion protein (VAP-1) were studied.  Transformation of VAP-1 into P. pastoris vectors and amine oxidase expression and purification in E. coli were explored.  Extensive experienced with protein crystallization screening, x-ray diffraction collection and processing, and x-ray protein structure solving and modeling with molecular replacement.  

 

Diffractions like these were collected using copper x-ray scattering from a Rigako RU-200 rotating anode generator equipped with Osmic mirror optics and the images were recorded on a Mar345 image-plate detector.

 

Once a full set of diffraction data is collected and the phase of the crystal is determined, then computer based programs can be utilized for data processing. A few rounds of refinement is needed before the final protein structure is solved.

 

June 2002 – September 2006   (top)

California Institute of Technology, Pasadena, CA USA. 

Co-expressed and purified calmodulin with mammalian nitric oxide synthase in E.Coli.  Designed and synthesized both channel and surface binding sensitizer-linked substrates for inducible nitric oxide synthase. Assayed for protein turnover of substrate with synthesized substrate analogs.  Characterized short lived intermediates produced by laser-induced electron transfer to the active site of the protein.  Successful wires delivered electrons into the active site and reduced Fe(III) to Fe(II) upon laser photolysis.   Designed and synthesized donor-bridge-acceptor molecular complexes (DBA wires) used to characterize ultra fast electron transfer with the purpose of proving the McConnell Tunnelling Model.  The wires are comprised of a ruthenium dipyridyl complex serving as the acceptor, an oligo-xylene bridge at various length, and an alkynyl methoxy aniline electron donor, all covalently linked. 

Nanosecond laser instrumentation can be set-up (shown below) to collect transient luminescence and transient absorbance measurements of short-lived species generated by laser pulses.

 

Example of a transient luminescence trace of inhibitor fluorescence quenching in the presence of protein.

 

Example of a transient absorbance trace of inhibitor fluorescence quenching in the presence of protein, producing a longer-lived intermediate species, indicative of an electron transfered species produced by electronic interactions between the inhibitor and the protein active site.

 

Resonance Raman laser instrumentation can be set-up (shown below) to collect vibrational signals of protein samples bound to the inhibitor.

 

Example of a resonance Raman trace of protein in the absence and presence of inhibitor before and after laser photoexcitation.

 

 

June 2000 – August 2001   (top)

Sweet Briar College, Sweet Briar, VA USA. 

Designed and synthesized platinum(II) and palladium(II) square planar complexes used as chemotherapeutic agents.   Bioactivity of M(dione)Cl2, M(dppz)Cl2, [M(dione)2][PF6]2, and [M(dppz)2][PF6]2 were explored, where M = Pt(II) or Pd(II).

 

 

 

TEACHING EXPERIENCES (top)

2008-2009  Sweet Briar College

TEACHING PHILOSOPHY (top)

As a student, one of the most memorable experiences I had at SBC were my time in the classrooms.  The ratio of students to teachers is unbeatable anywhere else.  I learned a lot in all of my courses, created close bonds with my professors, and discovered a lot about myself in such intimate environments that SBC creates for its students.  I have always desired to give back to the SBC community and to influence all future students by being in the same situation but in reverse.

To be a great teacher is not only to teach a particular subject well, but also to be an advisor, a mentor, and a role model.  Through my scientific career, I have developed a strong belief in furthering the presence of women in science.  Even to this day, the question remains, are women gaining equality in the sciences?  I believe that I can do an incredible job at making the science readily accessible to my students, at teaching them to understand and articulate the information, and athelping them to develop an interest for science to further women’s presence in the field.

I have a passion for interdisciplinary learning.  By using research as a tool for teaching, I intend on opening my students’ potential towards the sciences by developing a research program that has a central focus on chemistry intertwined with its permeability into all fields of science, such as physics, biology, and engineering.  As we advance further into the future, the scientific divisions begin to permeate each other creating ‘sub’ – fields commanding scientists to utilize critical thinking skills in multidisciplinary subjects.  Owing to my diverse background, from my undergraduate research in inorganic synthesis to my graduate studies in bioinorganic and biophysical research and then finally onto my postdoctoral physical chemistry research in x-ray crystallography, I am comfortable teaching all fields of chemistry: organic, inorganic, bioorganic, bioinorganic, biophysical, and physical chemistry.  My proposed research focus will be fundamentally chemistry and its roles in biological, physical, and engineering problems.  Having the opportunity to use research as a tool for teaching will greatly help the students toward their development as young scientists. 

To be a prominent member of the SBC community is not to only be involved in the students’ academic and extracurricular activities inside the school, but also to be involved in creating a good presence of SBC women in its surrounding community.  I intend on teaching and guiding SBC women in becoming role models themselves to preteen girls by starting a Girls-on-the-Run council involving the Sweet Briar community with its surrounding areas.  Girls-on-the-Run (http://www.girlsontherun.org/) is an international non-profit prevention program that encourages preteen girls to develop self-respect and a healthy lifestyle through running with suitable role models, such as SBC women.  These preteen girls from the surrounding schools will be matched with the SBC volunteers for an after school program that involves training for a 3-5K running event with self-esteem enhancing and uplifting workouts, focusing on their physical, emotional, mental, social, and spiritual well-being.  This program will connect SBC women with its community and encourage higher quality and life changing experiences for everyone involved. 

Sweet Briar women are crème de la crème and I would like to see that all SBC students remain among the top and become a strong woman leader in their community.  SBC represents a standard that I deeply respect and creates the only reason why I want to teach. 

 

PUBLICATIONS (top)

• Nguyen, Y.H.L.; Winkler, J.R.; Gray, H.B. Utilizing Channel and Surface Binding Sensitizer – Linked Wires to Probe Heme Coordination States of Inducible Nitric Oxide Synthase.  Manuscript in preparation.
  
  
• Glazer, E.C.; Nguyen, Y.H.L.; Gray, H.B.; Goodin, D.B. Probing Inducible Nitric Oxide Synthase with a Pterin-Ru(II) Sensitizer Wire.  Angewandte Chemie International Edition (2007); 120; 5; 912-915. (PDF)
  
  
• Contakes, S.M.; Nguyen, Y.H.L.; Gray, H.B.; Glazer, E.C.; Hays, A-M.; Goodin, D.B. Conjugates of Heme-thiolate Enzymes with Photoactive Metal-Diimine Wires. Structure & Bonding: Photofunctional Transition Metal Complexes, Vol. 123, Yam, V.W.W. (Ed.), Springer-Velag (2007), XII, 259p. (PDF)
  
  
• Nguyen, Y.H.L.; Winkler, J.R.; Gray, H.B. Probing Heme Coordination States of Inducible Nitric Oxide Synthase with a Re(I)(imidazole-alkyl-nitroarginine) Sensitizer-Wire. J. Phys. Chem. B (2007); 111; 6628-6633. (PDF)
  
  
• Belliston-Bittner, W.; Dunn, A.R.; Nguyen, Y.H.L.; Stuehr, D.J.; Winkler, J.R.; Gray, H.B.. Picosecond Photoreduction of Inducible Nitric Oxide Synthase by Rhenium(I)-diimine Wires.  J. Am. Chem. Soc. (2005); 127; 15907-15915. (PDF)
  
  
• Udit, A.K.; Belliston-Bittner, W.; Glazer, E.C.; Nguyen, Y.H.L.; Gillan, J.M.; Hill, M.G.; Marletta, M.A.; Goodin, D.B.; Gray, H.B. Redox Couples of Inducible Nitric Oxide Synthase. J. Am. Chem. Soc. (Communication) (2005); 127(32); 11212-11213. (PDF)
  
  
• Granger, R.M.; Davies, R., II; Wilson, K.A.; Kennedy, E.; Vogler, B.; Nguyen, Y.; Mowles, E.; Blackwood, R.; Ciric, A.; White, P.S.  A new cis-platin analog? The synthesis, characterization, selective cytotoxicity and DNA binding studies of tetrachloro (1,10-phenanthroline-5,6-dione) platinum(IV); X-ray structure analysis of dichloro(1,10-phenanthroline-5,6-dione)platinum(II).  Journal of Undergraduate Chemistry Research (2005); 4(2), 47-56.

 

SELECTED PRESENTATIONS (top)

2008

• Alien Invasion in the Membrane : assimilating alien amphiphiles into integral membrane proteins (IMP) for crystallization. Sweet Briar College FA2008 HONORS Colloquia. Sweet Briar, VA USA.
  October 15, 2008. (oral presentation, PDF)
• Structural Intermediates Directing Mechanistic Insights to Benzylaminoacetamide Inhibition of Copper Amine Oxidase. Gordon Research Conference : Metals in Biology. Ventura, CA USA.
  January 28 - February 2, 2008. (poster presentation, PDF)
• Structural Evidence of 2,3-Butadienylamine Inhibition of Copper Amine Oxidase. Gordon Research Conference : Protein Cofactors, Radicals and Quinones. Ventura, CA USA.
  January 20 - 25, 2008. (poster presentation, PDF)

2007

• Arylhaloallylamine Complexes of Copper-Containing Amine Oxidases. 13th International Conference on Biological Inorganic Chemistry. Vienna, Austria. July 15-20, 2007. (poster presentation, PDF)
• Sensitizer-linked Substrates as Mechanistic Probes for Inducible Nitric Oxide Synthase. 33rd Lorne Conference on protein Structure and Function. Lorne, SA AU.
  February 4 - 8, 2007. (poster presentation, PDF)

2006

• Surface Binding Wires for Inducible Nitric Oxide Synthase. ACS National Meeting and Expo. San Francisco, CA USA. September 10- - 14, 2006. (poster presentation, PDF).
• Wiring Inducible Nitric Oxide Synthase. Gordon Research Conference : Bioinorganic Chemistry Graduate Research Seminar. Ventura, CA USA. February 2 - 5, 2006. (oral presentation, PDF)
• Wiring Inducible Nitric Oxide Synthase. Gordon Research Conference : Metals in Biology. Ventura, CA USA. January 29 - February 2, 2006. (poster presentation, PDF)
• Rhenium wires for iNOS. Symyx Technologies, Inc. Santa Clara, CA USA.
  August 28, 2006. (oral presentation, PDF)

2005

• Arginine linked rhenium wires for inducible nitric oxide synthase. 12th International Conference on Biological Inorganic Chemistry. Ann Arbour, MI USA.
  July 31- August 5, 2005. (poster presentation, PDF)
• Rhenium wires for iNOS. Gordon Research Conference : Nitric Oxide. Lucca (Barga), Italy.
  May 22 - 27, 2005. (poster presentation, PDF)

2004

• Sensitizer-linked substrates for iNOS. Southern California Inorganic Photochemistry Conference.
  Catalina Island, CA USA. September 2004. (oral presentation, PDF)
• Sensitizer-linked substrates for iNOS. ACS National Meeting and Expo. Philadelphia, PA USA.
  August 22 - 25, 2004. (poster presentation, PDF)

2003

• Electron Tunneling Wires. Southern California Inorganic Photochemistry Conference.
  Catalina Island, CA USA. November 2003. (oral presentation, PDF)

 

REFEREED FOR JOURNALS (top)

Acta Crystallographica Section F

Journal of Undergraduate Chemical Research

 

 

 

 

 

**********************

This site is maintained by Yen Hoang Le Nguyen, PhD
Assistant Professor of Chemistry, Department of Chemistry,
Sweet Briar College, Sweet Briar, VA 24595
Please direct comments to Yen at ynguyen@sbc.edu
last updated : 11.01.08

**********************