Drug and Drug Target Discovery
Searching for new drugs against diseases, cancer and microbes; use of comparative genomics to find potential drug targets.
Investigating survival strategies of bacterial persisters
Bacteria can utilize a diverse repertoire of strategies to survive stress, including those imposed by antimicrobials present in their natural habitats and in clinical settings. Research in the Mok Lab focuses on the survival strategies of bacterial persisters, which are rare subpopulations in clonal cultures that can survive antibiotic doses lethal to their kin. We use genetic, biochemical, and systems approaches to elucidate bacterial responses that contribute to antibiotic persistence and develop strategies to sabotage these culprits of recalcitrant infections.
Mining Microbial Symbioses for Drug Discovery
Jonathan Klassen studies microbial community ecology, especially using the fungus-growing ant symbiosis as a model system to understand how microbial interaction networks evolve. Because these interactions are poorly studied and often mediated by natural products, they are a fertile source for discovering novel compounds. The Klassen lab couples genomic and chemical techniques to characterize the molecular bases of these interactions and exploit them for drug discovery, and contextualizes them within their ecological niches to understand and test their evolution.
Understanding drug metabolism by the gut microbiome
The Na Li lab is interested in studying how the human gut microbiome interact with orally ingested drug and bioactive compounds as well as their health outcomes, with an aim of improving the efficacy and minimizing interpersonal variations of oral drugs. We use a variety of chemical and biological approaches to study the role of the gut microbiome as an organ of metabolism.
Alfredo Angeles-Boza’s research group investigates the role of the Amino Terminal Copper and Nickel binding motif in antimicrobial peptides. We have identified this motif in antimicrobial peptides isolated from tissues and cell types of many forms of life, from fungi and invertebrates to plants and vertebrates. We are interested in learning from these systems to design new and effective antibacterial and antifungal agents. We use chemical and biochemical techniques to determine the effect of the chemical structure on the antimicrobial activity of the peptides. A particular strength of our group is our “inorganic chemistry” approach.
Arthur Günzl’s research team focuses on gene expression mechanisms in the eukaryotic, unicellular parasite Trypanosoma brucei which differ substantially from the correponding mammalian processes, depend on extremely divergent protein factors, and enable the parasite to evade the mammalian immune system by Antigenic Variation. We use biochemical, genetic and imaging techniques to study these processes and factors. A particular strenght of our group is the purification of protein complexes by tandem affinity purification.
Marcy Balunas’ lab investigates the chemistry and biological activity of marine microorganisms with a unique focus on the microbiology and natural products chemistry of tunicate-associated and psychrophilic marine and glacial bacteria. We are interested in the microbial dynamics in marine tunicates, especially as related to the sequestration, inheritance, and function of the bacterial communities associated with marine tunicates. Our approach includes both chemical (e.g., extraction, compound isolation, HPLC, LC-MS, NMR) and biological (e.g., pathogenic biological assays, 16S rRNA deep sequencing) techniques.
Leslie Shor’s research group studies microbial systems influenced by micro-scale habitat features. We have been developing a biofilm screening assay to measure respiratory responses of Staphyloccus aureus biofilms in response to concentrations, delivery rates, and combinations of antimicrobials. The motivation for the work is that bacterial pathogens commonly live as a structured hydrogel-encased community called a biofilm. Bacteria in a biofilm are more tolerant to antimicrobials, but it has been difficult to measure susceptibility of biofilm bacteria.Enabling technologies for this work include: (i) a spatially continuous, non-destructive oxygen sensing film, (ii) contact printing methods to create biofilm arrays, (iii) micro-scale reaction and diffusion modeling. In collaboration with industrial partners, we are also investigating methods to culture pure and mixed-species biofilms for screening antimicrobials for personal care and industrial applications.
Research in the lab of Dennis Wright is broadly focused on the development of small organic molecules with important biological activity, both as potential new therapeutics and probe molecules to better understand biological systems. Central to this program is a strong interest in synthetic organic chemistry that allows us to explore the relationships between molecular structure and function and provides us with many opportunities to develop new methods and strategies. As my research has evolved over the years, it has become increasingly collaborative and interdisciplinary, adding new areas or research including structure-based drug design and high-throughput screening as critical enhancements to our program in medicinal chemistry. Our points of departure for these studies can be conveniently divided into three general areas of interest; bioactive natural products, structure-based drug design and small molecule library design and screening.