Manal A. Swairjo, Ph.D.
Graduate College of Biomedical Sciences
Phone: 8201 | Join year: 2010
1988 B.Sc. Physics and Mathematics,
1996 Ph.D. Cellular Biophysics, Boston University.
Courses taught and/or directed:
- Biological Systems in Human Disease, 18-week course offered to 1st year MS students and covers comprehensively human anatomy and physiology from the molecular, cellular, tissue, to the system level, focusing on homeostasis and disease.
- Introduction to Biotechnology, 18-week hands-on laboratory-based methods course offered to 1st-year MS students.
- Medical biochemistry to 1st- and 2nd-year medical students: topics in biochemistry of the gastrointestinal system, nutrition absorption and assimilation, metabolism and inborn errors of metabolism.
For classroom teaching, I emphasize problem-based learning and utilize discussion groups, standardized patients demonstrations and multimedia tools. My teaching efforts at WesternU included all aspects of course design, setting teaching and learning objectives, preparing materials, designing and implementing classroom assessment tools, lecturing and exams, and course assessment.
GCBS 5080 Biological Systems in Human Disease - Part 1
GCBS 5060 Introduction to Biotechnology
My research focuses on tRNA biogenesis processes and their links to human disease. tRNA is an ancient molecule that evolved to be the adapter between amino acids and codons, thus mediating the translation of the genetic code. The coding properties of tRNA do not reside only in its primary sequence. Post-transcriptional nucleoside modification, particularly in the anticodon-stem loop (ASL) region of tRNA, are required for cognate and/or wobble codon recognition and translocation, they enhance aminoacylation properties of tRNA, and prevent ribosomal frameshifting.
Deficiencies in tRNA modifications cause a variety of diseases, e.g. hereditary human mitochondrial disease, and modified nucleosides serve as sensitive human cancer markers. Most significantly, modifications of the anticodon-stem loop have been implicated in viral replication as several retroviruses rely on modifications of host cell tRNA for virulence or to replicate.
In the past five years, my lab focused on elucidating the biosynthesis pathways of three modified tRNA nucleosides: queuosine (Q), archaeosine (G+), and threonylcarbamoyl adenosine (t6A). Studying these pathways in model microbial systems, in which some of the genes involved are essential, has led to the discovery of several new potential antimicrobial drug targets, as well as new enzymatic mechanisms and unprecedented chemistries such as biological nitrile reduction. Our approach combines X-ray crystallographic, structural bioinformatic and biochemical analyses, complemented by collaborations with geneticists and chemists.
A. In peer-reviewed journals
1.Swairjo M.A.,Rothschild K.J., Nappi B., Lane A. & Gold H. (1991). Infrared fiber optic sensors: New applications in biology and medicine. Applied Spectroscopy in Material Science1437: 60‑5.
2.Swairjo M.A., Seaton B.A. & Roberts M.F. (1994). Effect of vesicle composition and curvature on the dissociation of phosphatidic acid in small unilamellar vesicles — a 31P‑NMR study. Biochimica et Biophysica Acta1191: 354‑61.
3.Swairjo M.A., Roberts M.F., Campos M.‑B., Dedman J.R. & Seaton B.A. (1994). 31P- and 1H‑NMR studies of the interaction of annexin V with small phosphatidic acid‑containing unilamellar vesicles. Biochemistry 33: 10944‑50.
4.Swairjo M.A., Concha N.O., Kaetzel M.A., Dedman J.R. & Seaton B.A. (1995). Crystal structures at 1.9 Å resolution of rat annexin V in complex with glycerophosphoserine or glycerophosphoethanolamine: modes of binding to phospholipid polar moieties. Nature Structural Biology 2: 968-74.
5. Campos M.B., Mo Y.D., Mealy T.R., Li C.W., Swairjo M.A., Balch C., Head J.F., Retzinger G., Dedman J.R. and Seaton B.A. (1998). Mutational and Crystallographic Analyses of Interfacial Residues in Annexin V Suggest Direct Interactions with Phospholipid Membrane Components. Biochemistry22: 8004-10.
6. Swairjo M.A., Towler E.M., Debouck C. & Abdel-Meguid S.S. (1998). Structural Role of the 30's Loop in Determining the Ligand Specificity of the Human Immunodeficiency Virus protease. Biochemistry 31: 10928-36.
7. Morales A.J., Swairjo M.A., & Schimmel P. (1999). Structure-Specific tRNA Binding Protein From the Extreme Thermophile Aquifex aeolicus. EMBO J.18: 3475-83.
8.Swairjo, M.A., Morales A.J., Wang C.-C., Ortiz A.R., & Schimmel P. (2000). Crystal Structure of Trbp111: a Structure-Specific tRNA Binding Protein. EMBO J.19: 6287-98.
9.Swairjo M.A.,Otero F.J., Yang X.-L., Lovato M.A., et al., Schimmel P. (2004). Alanyl-tRNA synthetase crystal structure and design for acceptor-stem recognition. Molecular Cell. 13: 829-41.
10. Lovato M.A., Swairjo M.A., Schimmel P. (2004). Positional recognition of a tRNA determinant dependent on a peptide insertion. Molecular Cell. 13: 843-51.
11.Swairjo M.A.and Schimmel P. (2005). Breaking sieve for steric exclusion of a noncognate amino acid from active site ofa tRNA synthetase. Proc. Natl. Acad. Sci. USA. 102: 988-93.
12. Van Lanen S.G., Reader J.S., Swairjo M.A., de Crécy-Lagard V., Lee B., Iwata-Reuyl D. (2005). From cyclohydrolase to oxido-reductase: Discovery of nitrile reductase activity in a common fold. Proc. Natl. Acad. Sci. USA.102:12, 4264-9.
13. Swairjo M.A., Reddy R.R., Lee B., Van Lanen S.G., Brown S., de Crécy-Lagard V., Iwata-Reuyl D., Schimmel P. (2005). Crystallization and preliminary X-ray characterization of the nitrile reductase QueF - a queuosine biosynthesis enzyme. Acta Crystallogr. F61: 945-8.
14. Yang X.-L., Otero F.J., Ewalt K.L., Liu J., Swairjo M.A., Köhrer C., RajBhandary U.L., Skene R.J., McRee D.E., Schimmel P. (2006). Two conformations of a crystalline human tRNA synthetase-tRNA complex: implications for protein synthesis. EMBO J. 25(12):2919-29.
15. El Yacoubi B., Bonnett S., Anderson J.N., Swairjo M.A., Iwata-Reuyl D., de Crécy-Lagard V. (2006). Discovery of a new prokaryotic type I GTP cyclohydrolase family. Journal of Biological Chemistry, 281(49): 37586–93.
16. El Yacoubi, B., Lyons, B., Cruz, Y., Reddy, R., Nordin, B., Agnelli, F., Williamson, J.R., Schimmel, P., Swairjo, M.A. and de Crécy-Lagard, V. (2009). The universal YrdC/Sua5 family is required for the formation of threonylcarbamoyladenosine in tRNA. Nucleic Acids Research, 37(9): 2894-2909.
17. Sankaran, B., Bonnett, S., Shah, K., Gabriel, S., Reddy, R., Schimmel, P., Rodionov, D.A., de Crécy-Lagard, V., Helmann, J.D., Iwata-Reuyl, D., and Swairjo, M.A. (2009). Zinc-Independent Folate Biosynthesis: Genetic, Biochemical, and Structural Investigation Reveal New Metal Dependence for GTP Cyclohydrolase IB. J. Bacteriology, 191(22): 6936–49.
18. Phillips, G., Chikwana, V.M., Maxwell, A., El-Yacoubi, B., Swairjo, M.A., Iwata-Reuyl, D., and de Crécy-Lagard, V. (2010). Discovery and characterization of an amidotransferase involved in the modification of archaeal tRNA. J. Biological Chemistry (paper of the week), 285(17):12706-13.
19. Harris, K.A., Jones, V., Bilbille, Y., Swairjo, M.A. and Agris, P.F. (2011). YrdC exhibits properties expected of a subunit for a tRNA threonylcarbamoyl transferase. RNA, 17(9):1678-87.
20. Phillips G., SwairjoM.A., Gaston K.W., Bailly M., Limbach P.A., Iwata-Reuyl D., de Crécy-Lagard V. (2012). Diversity of archaeosine synthesis in Crenarchaeota. ACS Chemical Biology, Feb 17;7(2):300-5.
21. Chikwana, V.M., Stec, B., Lee, B.W.K., de Crécy-Lagard, V., Iwata-Reuyl, D. and Swairjo, M.A. (2012). Structural basis of biological nitrile reduction. J. Biological Chemistry, 287:30560-70
22. Elmadhoun, B.M., Swairjo, M.A., and Burczynski, F.J. (2012). Fluorescent fatty acid transfer from bovine serum albumin to phospholipid vesicles: collision or diffusion mediated uptake. J. Pharmacy & Pharmaceutical Sciences. 15(3): 420-32.
23. Swairjo M.A. and Seaton B.A. (1994). Annexin structure and membrane interactions: a molecular perspective. Annual Reviews for Biophysics and Biomolecular Structure. 23: 193‑213.
24.Swairjo M.A. (1998) Anti-Factor IX Fab Fragment Crystal Structure and Methods of Use for Peptidomimetic Design. U.S.A. Patent.
25.Swairjo M.A.,Iwata-Reuyl D., de Crecy-Lagard V. (2008) Novel GTP cyclohydrolase type IB(WO 2010/039115). U.S.A. and international patent.
26.Swairjo M.A., Iwata-Reuyl D. (2009) Crystal Structure of Queuosine Biosynthesis Enzyme QueF Bound to Substrate PreQ0. Provisional application.
27. Swairjo M.A.,Iwata-Reuyl D., de Crecy-Lagard V. (2008) Novel GTP cyclohydrolase type IB (No. 2010-532094) Japanese patent.