Hyerim Ban, UMass Fellow 2021-2022
Graduate Program: Molecular and Cellular Biology
Lab: Lauren Andrews and Jessica Schiffman
Research Interests: Developing new approaches for genetic manipulation across the genome-wide scale for engineering cell responses and aiding the design of material properties
Catheter-associated urinary tract infections (CAUTIs) are the most common hospital-acquired infections. Polymer-based implantable biomedical devices, such as urinary catheters, can become infected by bacteria, which adhere to the surface, form a biofilm, and result in infection. Uropathogenic E. coli (UPEC) strains are the pathogens most commonly responsible for these infections. Since broad spectrum of antibiotics are the main treatment of UTI, these infections have been linked to increasing prevalence of antibiotic-resistant strains, causing these infections to be difficult to treat and limiting treatment options. Here we propose an alternative solution that leverages the rational development of anti-infection catheter coatings as well as an improved understanding of genes that control the formation of these infections in clinical UPEC strains and across biomaterials surfaces. Whereas prior studies have largely focused on subsets of genes related to adhesion and biofilm formation, my project will employ a genome-wide approach using Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and a deactivated Cas nuclease for controlled and targeted gene repression. To date, genetic tools and characterized genetic parts in these clinical UPEC strains is quite limited. After developing these genetic tools, I will utilize quantitative genome-wide functional screening to identify genetic targets that alleviate cell attachment and disrupt biofilm formation in UPEC strains across systematically varied biomaterial properties.
An overarching goal of my project is to create a new interdisciplinary approach to apply materials science and synthetic biology tools to engineer and design the material properties and the cellular response at clinically relevant microbe-material biointerfaces. My project aims to determine the design rules for CRISPR interference (CRISPRi) repression in clinical UPEC bacteria. Based on these developed CRISPRi rules, I will design and build CRISPRi pooled genome-wide libraries for clinical UPEC strains. Using pooled cell adhesion assays, I will identify genes responsible for bacterial attachment across a set of biomaterial surfaces with varied material properties. By identifying genes responsible for adhesion of uropathogenic E. coli across different implantable biomaterial surfaces, this work has great potential to be used as foundation for the development of improved implantable biomaterials to prevent and treat catheter-associated infections.