Manal Swairjo, Ph.D.
Pronouns: Manal
Professor of Biochemistry
San Diego
Primary Email: [email protected]
Building/Location
5500 Campanile Dr
San Diego,
CA
92182
Mail Code: Links
Bio
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.
Areas of Specialization
Biochemistry, X-Ray Crystallography, Structural Bioinformatics