- Assistant Professor, Department of Chemistry
- Affiliate Member, The University of Chicago Comprehensive Cancer Center
PhD, University of California, Berkeley, 2010
Research in the Dickinson lab lies at the interface of chemistry, biology, and engineering. We exploit our expertise in synthetic chemistry, protein engineering, molecular evolution, and cell biology to design and deploy new technologies for the interrogation of biological systems. Specifically, we seek to develop new methods to monitor and modulate chemical reactions in live mammalian cells, with a focus on decoding mammalian metabolic regulatory mechanisms. Synthetically derived small molecule fluorescent probes, engineered transcription-based protein sensors, and enzymes reprogrammed through continuous evolution currently constitute the three primary research efforts of the lab. All members of the lab will pursue their research projects in a highly interdisciplinary, collaborative, and collegial environment, forming a solid foundation for modern research in the field of chemical biology.
1. Synthesis and application of small molecule fluorescent probes for molecular imaging of deacylases. Although hundreds or more proteins in the human proteome are subjected to regulation by lysine and cysteine acylation reactions, these diverse modifications are regulated by a relatively small number of enzymes. Therefore, we seek to address the fundamental questions: how do cells regulate deacylation activities and how do those modifications modulate cell signaling? To accomplish this, we are synthesizing new classes of chemical tools that report on or modulate deacylation activities in living cells. Initial efforts will focus on understanding the role of spatial distribution and subcellular localization in modulating deacylation activities, specifically dealing with metabolic regulation.
2. Encoding chemistry in polynuceotides with engineered molecular sensors. Current methods to monitor biochemical activities in live cells generally rely on optical reporters, impeding multiplexed analyses of biological systems. We have developed a new sensing strategy using engineered molecular recording devices, Activity-Responsive RNA Polymerases (AR-RNAPs), which respond to specific biochemical events by producing defined sequences of RNA. The RNA signals can then be “read” by high-throughput sequencing (HTS) for multidimensional molecular analysis or integrated into gene circuits for tailored therapeutics. Analyzing biochemistry in live cells using sequencing represents a new paradigm in biosensing technologies, and will synergize with synthetic biology approaches to develop next-generation “smart” therapeutics and clinically deployable diagnostics. Currently, the group is working toward creating devices to encode protease activities, kinase activities, and protein-protein interactions in defined sequences of RNA in live cells.
3. Reprogramming proteins through continuous directed evolution. Evolution is a powerful mechanism with which to endow biomolecules with user-defined activities. However, traditional directed evolution approaches often fail to produce molecules with desired levels of activity, mainly due to limitations to the number of rounds of evolution that can be reasonably performed toward a particular evolutionary goal. Our group deploys Phage-Assisted Continuous Evolution (PACE) to reprogram important classes of biomolecules to produce novel research tools, starting points for therapeutics, and model systems for the study of evolution. We have developed systems to reprogram protein-DNA interfaces and are now working on developing new continuous evolution strategies to evolve protein-protein interactions, specifically focusing on heterodimeric enzyme formation.