JULY 1, 2020
Michigan Drug Discovery has awarded funding which will continue utilization of the NPDC. James Moon, John Gideon Searle Associate Professor of Pharmaceutical Sciences in the College of Pharmacy, will continue his ongoing work to develop immunotherapy agents for the treatment of cancer. Over the past year, during the screening process of over 10,000 natural product extracts in the NPDC, several were identified with potent immune-stimulating activity. Moon’s new funding will provide support for further in-depth research of the most interesting extracts, including structural characterization of the active component natural products, as well as scale-up for additional research and development.
May 11, 2020
Serratia marcescens is a bacterium frequently found in the environment, but over the last several decades has evolved into a concerning clinical pathogen, causing fatal bacteremia. To establish these infections, pathogens require specific nutrients—one very limited but essential nutrient is iron. We sought to characterize the iron acquisition systems in S. marcescens isolate UMH9, which was recovered from a clinical bloodstream infection. Using RNA-sequencing (RNA-seq), we identified two predicted siderophore gene clusters (cbs and sch) that were regulated by iron. Mutants were constructed to delete each iron acquisition locus individually and in conjunction, generating both single and double mutants for the putative siderophore systems. Mutants lacking the sch gene cluster lost their iron-chelating ability as quantified by chrome azurol S (CAS) assay, whereas the cbs mutant retained wild type activity. Mass spectrometry-based analysis identified the chelating siderophore to be serratiochelin, a siderophore previously identified in Serratia plymuthica. Serratiochelin-producing mutants also displayed a decreased growth rate in iron-limited conditions created by dipyridyl added to LB medium. Additionally, mutants lacking serratiochelin were significantly outcompeted during co-challenge with wild type UMH9 in the kidneys and spleen after inoculation via the tail vein. This result was further confirmed by an independent challenge in a bacteremia mouse model, suggesting that serratiochelin is required for full S. marcescens pathogenesis in the bloodstream. Nine other clinical isolates have at least 90% protein identity to the UMH9 serratiochelin system; therefore, our results are broadly applicable to emerging clinical isolates of S. marcescens causing bacteremia.
NOVEMBER 23, 2019
• Antibiotic resistance presents a multifaceted health challenge to entire world.
• Newer approaches and more effective antibacterial targets are required to combat this threat.
• Coenzyme A (CoA) biosynthesis in particular may represent an effective antimicrobial target.
• Natural products have been at the forefront of antibacterial drug discovery.
• Alkyl-resorcinol class of molecules could be an attractive class to develop as anti-bacterial.
SEPTEMBER 25, 2019
This summer, NPDC researchers Amy Fraley, Andrew Robertson and Ashu Tripathi led a group of U-M undergraduates through entire process of drug development, from environmental collection at the U-M Biological Station, to laboratory extraction, analysis, and eventual application. Learn more about what they accomplished.
SEPTEMBER 24, 2019
Diving for Discovery! Check out the link to get an idea about what we are up to......
SEPTEMBER 13, 2019
The Natural Products Biosciences Initiative is currently seeking outstanding discovery scientists to fill two positions; one at the rank of Assistant Professor, and one at the Associate Professor or Full Professor level. We are particularly interested in applications with a focus on natural products research relating to synthetic biology, and the microbiome link to human health and disease.
AUGUST 1, 2019
Welcome to Andrew Robertson, our new Post-Doctoral Research Associate. Andrew will be working with the NPDC on new drug discovery projects, starting with the two MDD projects awarded this month. He joins us from the Sherman Lab where he has worked for the past two years.
JULY 23, 2019
Michigan Drug Discovery has awarded funding of two projects, which will utilize the services of the NPDC. The first project award went to Daniel Lawrence, Frederick G.L. Huetwell Professor of Basic Research in Cardiovascular Medicine in the Medical School, to discover novel natural products therapeutics for treating fibrotic diseases. The second project award went to James Moon, John Gideon Searle Associate Professor of Pharmaceutical Sciences in the College of Pharmacy, to identify defined natural products to help activate the innate immune system as an anti-tumor response.