Research in the Orjala Lab pertains to the discovery of novel anticancer and antimicrobial metabolites from freshwater cyanobacteria using genomic tools, mass spectrometry and spectroscopic techniques.
UIC Strain Library
Drug discovery begins in the field, where soil samples and fresh blooms are brought back to the lab. Single filaments of cyanobacteria are isolated from these environmental samples, where they eventually become a unique strain in the library.
The UIC Strain Library is a vast collection of over one thousand strains of cyanobacteria collected from freshwater and estuarine environments around the world. Over one hundred strains added to the library each year.
The Orjala Strain Library is one of the largest repositories of North American freshwater cyanobacteria in the United States. Environmental samples are collected from diverse environments such as temperate lakes, rainforests, savannas, boreal forests and subtropical wetlands.
Drug Discovery & Metabolomics
A drug discovery research pipeline is utilized to identify novel pharmacological lead compounds produced by the UIC Strain Library. Library strains are grown at large scale, chemically extracted and then separated into fractions by chromatography. These fractions are screened against various bioassays. Novel bioactive leads are structurally elucidated using mass spectrometry and nuclear magnetic resonance (NMR) spectroscopy.
Lead compounds with antimicrobial and anticancer bioactivity are routinely identified from the UIC Strain Library. Drug leads commonly include alkaloids, cyclophanes, cyclic and linear peptides. Potent drug leads from this culture collection have featured halogen atoms and rare scaffolds containing isothiazole and oxadiazine functional groups.
Current research also includes the use of comparative metabolomics and molecular networking to facilitate drug discovery by exploring secondary metabolite expression from cyanobacteria by varying environmental stimuli.
Researchers have access to state-of-the-art NMR and LC-MS/MS instrumentation through collaborations with the Center for Structural Biology (CSB) and the Institute for Tuberculosis Research at UIC (ITR).
The UIC Strain Library is taxonomically and chemically diverse. Researchers assess relative phylogenetic coverage of the library via gene-based methods. The phylogenetic diversity of the Strain Library is currently being characterized by 16S rRNA sequencing, a well-established tool to evaluate prokaryotic phylogeny, with data continuously added to NCBI.
Previous work in this area has included the assignment of cyanobacterial biosynthetic gene clusters to its cognate secondary metabolite by
15N stable isotope labeling and metabolomic comparison using LC-MS.
Molecular biology research is supported through partnership with the Genome Research Division of the Research Resources Center at UIC. The GRC houses high-technology instrumentation and provides services such as Sanger sequencing and Next Generation Sequencing (NGS).