Small proteins play an outsized role in biology. They act as antibacterials, signaling factors of our immune, endocrine, and central nervous system, and are foundational in microbial community and bacteria-host interactions. However, finding and characterizing small proteins and peptides is challenging. Their small size often leaves them overlooked in genomic studies and makes them hard to isolate from natural sources or produce synthetically. Theses challenges have resulted in relatively few small proteins and peptides being discovered and characterized despite the vast numberers predicted. This lack of knowledge prevents us from understanding the functional diversity of unrecognized masses of small proteins and peptides that could defend against pathogen invasion and influence host cell functions. We are developing principles and tools to uncover, study, and deliver natural and synthetic small proteins and peptides that control bacterial growth and communication, and amplify beneficial host interactions. Current projects include:

Uncovering microcin diversity and functions

Microcins are potent and selective small protein antibacterials used in microbial competition. However, few have been identify. We are developing high throughput computational and experimental methods to uncover and characterize the diversity of microcins across Gram-negative bacteria. We explore their unique mechanisms of action, rare ability to translocate across bacterial membranes, host interactions, and potential to fight infection.

Developing synthetic peptide antibiotics

Natural and synthetic macrocyclic peptides provide new antibiotic scaffolds targeting many essential bacterial processes. We combine molecular screening with machine learning to speed the discovery of antibacterial macrocyclic peptides and understand how their sequence controls their activity. 

Building bacterial display and secretion systems

The discovery and implementation of bioactive peptides and small proteins requires advancement in computational and experimental screening. We are developing bioinformatic tools to improve the discovery process and bacterial display and secretion systems to uncover bioactive peptides and small proteins across natural and synthetic sequence space.

Designing bacteria-host interactions

Bacteria colonize diverse of host niches where they often interact with other microbes. We are designing systems that enable bacteria to display and release bioactive small proteins and effect neighboring microbes or influence host cell functions during colonization.

Investigating antibacterial nanobodies

Antibodies are known for their ability to selectively bind bacteria. But finding antibodies that can directly kill bacteria has been elusive. We are developing single-chain antibodies, called nanobodies, with direct antibacterial activity against Gram-negative pathogens.