Bugni Research Group
Tim Bugni’s research interests are marine natural products chemistry, symbiotic microorganisms, drug discovery, metabolomics, and NMR and MS for structure elucidation of novel natural products.
Genetically encoded small molecules, natural products, have been a valuable source of therapeutics particularly in the areas of cancer and infectious disease. However, discovering novel natural products has become significantly more difficult even though whole genome sequencing has shown that only a small fraction of microbial-produced natural products have been discovered. To overcome these difficulties, we are utilizing under-explored niches for bacterial cultivation and developing metabolomics approaches to enable discovery of novel natural products. We have cultivated bacteria from marine invertebrates such as sponges and ascidians. Many of these bacteria show great promise as sources of novel therapeutics. Using metabolomics, we prioritize the most promising strains for discovery of novel natural products as therapeutics in the areas of neurodegenerative disease, infectious disease, and cancer. For additional information, please see the lab website.
The overarching goal of our long-term research plan is to develop diverse natural product libraries from unique microbes for the purposes of drug discovery. Identification of novel therapeutic leads provides opportunities for synthetic modification to understand and relate the structure to a biological response and alter the pharmacological properties. Exploring lead compounds not only in terms of drug development, but also in terms of chemical biology and molecular pharmacology will provide opportunities to produce chemical probes that can be used to investigate cellular function.
Many natural products isolated from whole marine animals, such as sponges and ascidians, are likely produced by symbiotic bacteria. In collaboration with Professor Eric Schmidt (University of Utah), we are developing new methods to evaluate total bacterial diversity and molecular diversity of whole animals. Additionally, we are developing analytical approaches to understand natural product diversity from cultivable bacteria with the goal of rapidly identifying the most promising strains for drug discovery.
With the goal of discovering new natural product scaffolds with therapeutic potential, we use a combination of assays to detect biological activity and chemoinformatics to guide our discoveries. In terms of chemoinformatics, we are applying metabolomics tools for the analysis of large numbers of bacterial produced natural products. Additionally, the laboratory uses state-of-the-art high-resolution mass spectrometry as well as ultra-sensitive NMR spectrometers to rapidly characterize natural products on nanomole to picomole scales.
High-throughput screening (HTS) has the potential to test large numbers of compounds in a single day (>25,000). Most HTS platforms are not compatible with many aspects of natural products. By employing a high level of automation in the laboratory, we are developing methods to produce high quality natural products libraries and associated tools for prioritization of hits.