The goal of this research is to access precision pharmaceuticals that can edit the microbiome to prevent microbe-associated cancers and improve therapeutic efficacy. In the last decade, the revelation that specific bacteria impact the occurrence, prognosis, and treatment of cancer has exposed a need for drugs that can target problematic microbes without compromising communities that are essential for patient health and effective immuno-therapies. In Nature, bacteria achieve this kind of selective community editing using natural products: small molecules that feature chemical structures and biological activities that have been honed through millions of years of evolution.

Over the last decade...

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The goal of this research is to access precision pharmaceuticals that can edit the microbiome to prevent microbe-associated cancers and improve therapeutic efficacy. In the last decade, the revelation that specific bacteria impact the occurrence, prognosis, and treatment of cancer has exposed a need for drugs that can target problematic microbes without compromising communities that are essential for patient health and effective immuno-therapies. In Nature, bacteria achieve this kind of selective community editing using natural products: small molecules that feature chemical structures and biological activities that have been honed through millions of years of evolution.

Over the last decade, I have demonstrated my unique aptitude in the discovery and directed evolution of microbial natural products, developing platform technologies to access molecules with desired structures and functions. In this proposal, I will develop leads and platforms for microbiome-editing agents through two parallel research directions. First, I will describe the structure and mechanism of a family of naturally adaptive precision antibiotics, providing molecules with programmable specificity to edit the microbiome. Second, I will use phage-assisted continuous evolution (PACE) to create a plug-and-play evolution and engineering platform for natural products, unlocking Nature’s antibiotic factories to create designer drugs. Through these research paths, I will discover, evolve, and engineer molecules that can edit microbiomes to prevent disease and enhance existing chemo- and immuno-therapies.

The Baylor College of Medicine is an ideal place to carry out this work, as my expertise will be complemented by colleagues within my affiliated departments and within the Alkek Center for Metagenomics and Microbiome Research. By unlocking natural mechanisms for microbial community control, we will provide precision antimicrobials and enable precision medicine for cancer prevention and treatment.

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