Some fantastic news came last week to the Caesar lab! We have received NSF funding for the next three years through the BRC-BIO program, a program dedicated to supporting pre-tenure faculty in building their research programs in biology or biology-adjacent fields at primarily undergraduate institutions. Perfect fit!
Our grant will focus on our bat microbiome project, in which we are exploring the bacteria that live on the skin of bats as natural producers of antifungals that may help to protect certain bats against the devastating fungal pathogen, Pseudogymnoascus destructans, the causative agent of "White Nose Syndrome," which has killed millions of bats in the last ~15 years. Our collaborator Paris Salazar-Hamm (and Co-Investigator on the grant) was part of a project in 2017 out of Diana Northup's lab at the University of New Mexico (UNM) that found that bats in New Mexico and Arizona caves possess bacteria as part of their skin microbiota that have antifungal effects on P. destructans. (Read the 2017 paper here) Since the project's start, there have been over a hundred strains investigated that have antifungal properties--but we don't know the chemistry behind this activity. My amazing former colleague at Northwestern University, Michael Mullowney, reached out to the UNM team to see if they were interested in collaborating to dig into the natural product production behind this observed antifungal effect.
Enter Caesar lab! Our role in the project is to investigate the chemistry of the antifungal strains from the bat microbiome using a combination of mass spectrometry based metabolomics, bioactivity-directed chemometric modeling, and genomic data. We hope to identify novel antifungal compounds that could protect against P. destructans and characterize their biosynthetic pathways as well (Aim 1 in the Figure below)
Proposed workflow for our NSF project. Figure made using BioRender.com
We also hope to expand the chemical profile of the bacterial strains in our collection through the development of ecologically inspired synthetic communities. In caves, energy-scarce environments lead to complex interactions between microorganisms, influencing microbial populations and encouraging development of new species and unique specialized metabolites. A bottleneck to accessing this untapped biosynthetic potential is the well-documented observation that most microbial biosynthetic pathways are transcriptionally inactive under laboratory conditions, likely because biosynthesis is energetically expensive and organisms grown in controlled monocultures lack the environmental cues required to induce metabolite formation. With the second Aim, we will produce mixed co-cultures of bacteria from the bat microbiome to elicit secondary metabolite formation.
This grant will also serve to expand our growing collaboration with Grand Caverns, where we will not only collect bacterial strains to grow a local Virginia collection and invetigate their antifungal activities and natural product potential, but we also plan to develop microbial ecology specialty tours and expand their museum with a microbial ecology exhibit. I'm so excited to spend more time in these amazing caves and learn more about the Cave and Karst of Virginia.
This grant will support at total of 17 students in paid research experiences (including helping us travel to get field training and to conferences to present our work), help develop the curriculum at JMU by incorporating natural products research into our courses, and develop a cave-based outreach exhibit at Grand Caverns. A huge thanks to the NSF for this opportunity to launch my natural products program here at JMU! I can't wait to get started!
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