Abstract: Nanopores are miniaturized electrical sensors with arguably the smallest detection volumes (sub-yoctometers, or below 10^-24 m³).[1]Detection of molecules using nanopores involves electrical monitoring of ion current flow through a pore using a pair of electrodes placed across the nanopore-containing membrane. Our group focuses on the use of nanopores that range from 1 to 10 nm in all dimensions (diameter and thickness). We fabricate such nanopores using a combination of state-of-the-art ultrathin membrane fabrication and focused electron beam irradiation using a transmission electron microscope. Recently, we have found that nanopore dimensions critically determine the quality of detection and discrimination of biomolecules. I will talk about our efforts to distinguish different types of tRNA molecules, RNA-drug complexes,[2]and proteins[3]. In addition, I will mention our efforts to control DNA transport through nanopores, useful for genomic mapping.[4]Finally, I will mention our studies that probe nucleosomal interactions and influence by epigenetic factors,[5]as well as our latest efforts in combining nanopores and optical waveguides for direct DNA sequencing from picogram-level genetic material

We present examples from our group where biophysical chemistry impacts unsolved problems in infectious diseases and auto-immune diseases. We start with bacterial biofilms, which are structured multi-cellular communities that are fundamental to the biology and ecology of bacteria. By using population tracking algorithms, we dissect bacterial social behavior at the single cell level.  We will also discuss how we can learn from innate immunity peptides to renovate antibiotic design, and make precision antibiotics and antibiotics against persister bacterial populations. Finally, we examine the pathological role of antimicrobial peptides in a range of autoimmune disorders.