Small molecules produced by actinomycete bacteria have been essential components of antibacterial drug discovery, providing us with greater than half of the antibiotics used in the clinic. However, the discovery of new drug leads is being outpaced by the development of antibiotic resistance to current medicines. In my lab, we have built a collection of aquatic bacteria and are using them to generate natural product antibiotic drug-leads for infectious diseases.
Our library: We use a MALDI-TOF MS-based bioinformatics pipeline (IDBac) developed in our lab to build a smart library of bacteria. IDBac ensures that each strain in our library is taxonomically diverse, and that we have minimized natural product overlap between entires, a major problem that has hindered discovery efforts to date! Our library contains >2,000 bacteria that cover four phyla and represent over 60 genera from across the globe.
Microbial Drug Lead Discovery Pipeline
Despite significant advances in nearly every stage of the NP drug discovery process, the front end has remained relatively constant for decades. Our lab is currently working to innovate these steps so that researchers can more intuitively mine the environment for drug leads.
What we do:
Using high-throughput robotics and bioinformatics to discover the next generation of antibiotics
For the past few years, we have created innovate methods to improve earlier stages of the antibiotic discovery process. This includes a mass spectrometry-based bioinformatics tool (IDBac) to minimize redundancy of NP production between isolates, and a dual sided agar plate assay (DAPA) which allows microorganisms to compete on opposing sides of a solid support in individual wells. To integrate these advances into a single pipeline, we developed a new Environment to Bioassay antibiotic discovery approach that combines high-throughput robotics with DAPA and IDBac to rapidly select, screen, and prioritize antibiotic-producing bacteria. This framework allows us to accomplish many stages of the microbial drug discovery pipeline directly from bacterial cell mass grown on multiwell plates in a semi-automated fashion and offers an advantage in terms of scale and capacity. This project has been integrated with educational outreach efforts in partnership with community centers from underserved areas of Chicago, such as the James Jordan Boys & Girls Club. There are three central components to the program – field work, applied science experiments, and environmental literacy – with the goal of inspiring students from marginalized backgrounds to become the next cohort of university STEM majors. Overall, we aim to demonstrate 1) the feasibility and efficiency of a new antibiotic discovery approach, and 2) that graduate-level research can be successfully integrated with community partnerships.