Vexler, Shelby

Shelby is in the Chemistry Graduate Program, and joined the CMB Training Program in 2022. 

Mentor: Dr. Irene Chen

Research project:

     Penicillin, the first antibiotic, has prevented countless deaths from bacterial diseases since its discovery in 1928. Almost a hundred years later, the misuse of antibiotics has led to bacteria evolving immunity against them. Worldwide, more than 1.2 million people died from antibiotic resistance (AR) infections in 2019. The CDC reported a 15% increase in AR infections during 2020 as the SARS-CoV-2 pandemic pushed healthcare facilities over capacity, leading to increased transmission of bacterial diseases.

     Bacteriophages, or “phages”, are viruses that infect bacteria and offer a potential solution to the rise of antibiotic resistance. However, some of the most well-studied phages are non-lytic and infection does not result in bacterial death, while other lytic phages are limited by their host range. Two innovations may allow M13, a well-studied and commercially available phage, to overcome these barriers. First, the genome of M13 can be engineered such that additional proteins can be fused to and expressed with the g3p protein, which is responsible for binding to E. coli hosts.  Such proteins include the receptor binding protein of other phages, specific to different bacterial species, or portions of antibodies, which allow a variety of new antigens to be targeted. Secondly, gold nanorods can be conjugated to the external coat protein, g8p, that covers the majority of M13. Gold nanorods can be synthesized to a specific size such that near infrared light, capable of passing through biological tissues, can excite their electrons; this energy is released as heat, killing any bacteria bound by a phage. This combination of phages and gold nanorods has been coined “phanorods”. I seek to further advance the phanorod technology by 1) investigating new targets, such as the polysaccharides covering the external surface of bacteria, and 2) expanding the treatment from external to internal bacterial infections.