Nathan Kuhlmann

Nathan Kuhlman
Program: Molecular & Cellular Biology
Advisor: Peter Chien, Ph.D.
Education: Benedictine University in Illinois, BS, Biochemistry & Molecular Biology,  2012-2016

Research Summary

With antibiotic resistance on the rise, the urgent need for novel therapeutics is rapidly growing. The CDC estimates that approximately 2 million people annually become infected by antibiotic resistant bacteria, of the infected, 23,000 of those individuals are killed as a result. To address this issue, several biotechnology companies from the U.S. and Europe have undertaken recent efforts to develop novel antibiotic treatments. Bacterial proteases and their regulators is an area of basic research that has the potential to address the issue of antibiotic resistance. Many of these protease systems and their regulators are conserved in pathogenic bacteria and are directly involved in regulating bacterial development. Therefore, we speculate that protease accessory proteins, otherwise known as adaptors, and the key regulatory substrates they interact with, can potentially translate into novel antibiotics that specifically target bacteria that undergo developmental transitions. Recently, our lab reconstituted a novel system that governs the cell cycle progression of Caulobacter Crescentus, our model organism of study (Figure 1). In this system, the stepwise assembly of adaptors onto an essential protease allows for the degradation of key regulatory proteins that control the life cycle of Caulobacter. However, the structural details of how this system works remains unclear. Using this novel system as a platform, the overarching goal of my research project is to uncover the structural details of adaptor hierarchymediated protein degradation. The basic research of my project will provide mechanistic details of how this novel adaptor hierarchy functions to bind and deliver key regulatory proteins and provide a framework for how these complexes might function in other bacteria. General quality control, cell cycle progression and various other physiological processes are governed by the targeted destruction of specific proteins by energy-dependent proteases and warrant further study. As part of my research, we actively collaborate with two labs. I currently work with the Strieter lab to understand the dynamics of this system through NMR studies. We also collaborate with Gabriel Lander, a Cryo-EM specialist at Scripps Research Institute, in an effort to structurally characterize the adaptor hierarchy.