Project Leader
The goal of Dr. Schultz’s research is to understand the evolution of cellular programs in light of their highly dynamic behavior. He has a special interest in the changes in gene regulation that allow antibiotic responses in bacteria to adapt to new ecosystems with remarkably different selective pressures, such as in the typical transition from natural environments to clinical settings. Combining theoretical and experimental approaches, he strives to uncover the design principles that allow regulatory networks to coordinate cellular processes in changing environments.
Dr. Schultz has a background in electrical engineering and training in a variety of computational methods. In his theoretical work, he studied the stochastic nature of gene regulation, from its molecular basis (Schultz et al, PNAS 2008), through the behavior of small networks (Schultz et al, PNAS 2007), to large networks in bacteria (Schultz et al, PNAS 2009). He made progress in bridging the global process of cell decisions to the local behavior of network motifs. In his experimental work, Dr. Schultz investigated how the expression of resistance genes is optimized for the onset of a response to maximize cell survival. Using a microfluidics device that he developed for imaging single cells as they are exposed to antibiotics, he found that, surprisingly, fast expression of the repressor of the E. coli tet efflux pump upon drug exposure determines the cell’s ability to survive abrupt shifts in tetracycline concentration (Schultz et al, Cell Systems 2017). Furthermore, he showed that this somewhat counter-intuitive strategy actually optimizes the dynamic behavior of the resistance mechanism.
Moving forward, he has started a multidisciplinary lab—hosted in the Department of Microbiology & Immunology at the Geisel Medical School at Dartmouth—as part of the Neukom Academic Cluster in Computational Science. The research in his lab goes beyond the conventional view of antibiotic resistance (namely, population growth under steady drug conditions) by investigating the evolution of responses that are optimized for dynamical efficacy. The cell’s ability to regulate gene expression to mitigate the costs associated with resistance allows the dissemination of response mechanisms throughout microbial ecosystems, even when in contact with the antibiotic, is rare and makes their eradication extremely difficult. Using experimental evolution, microfluidics, bioinformatics and quantitative modeling, he seeks to identify the evolutionary pressures driving the emergence of complex regulation in antibiotic-resistance mechanisms in bacteria—a problem with wide clinical implications. He uses the establishment of P. aeruginosa chronic infections in the cystic fibrosis lung as a model to study the adaptation of environmental strains to a clinical setting, uncovering the new mechanistic designs that increase antibiotic resistance in opportunistic pathogens and guiding new treatment regimens that exploit the limitations of these resistance mechanisms in dealing with changing conditions.
In addition to his research, Dr. Schultz is strongly committed to graduate student training and education. He has experience teaching classes from the high-school to graduate levels. He is involved in the promotion of science in the media, and is a successful mentor of students in research. His strong background in mathematics and engineering, with graduate work in chemistry, physics and biology, allows him to approach scientific questions in an interdisciplinary context.