Bryan C. Dickinson Assistant Professor

Born Baltimore, MD 1984
University of Maryland, College Park, B.S. in Biochemistry, 2005
University of California, Berkeley, Ph.D. in Chemistry, 2010
Postdoctoral Fellow, Harvard University, 2011-2014

Accolades

2014 Young Investigator Award, Cancer Research Foundation

2013 American Chemical Society Nobel Laureate Signature Award

2011 Jane Coffin Childs Memorial Fund for Medical Research Fellowship

2011 NIH Individual Postdoctoral Fellowship (declined)

2010 Ash Stevens Outstanding Poster Award, Bioorganic Gordon Research Conference

2005 Departmental Honors, Chemistry and Biochemistry, University of Maryland, College Park

2005 Honors Citation, Environmental Studies, University of Maryland, College Park

2005 Alpha Chi Sigma Award, University of Maryland, College Park

2005 Spirit of Maryland Award Finalist, University of Maryland, College Park

2005 Phi Kappa Phi Honor Society, University of Maryland, College Park

2004 Howard Hughes Medical Institute Undergraduate Research Fellowship

2003 Joint Institute of Food Safety and Applied Nutrition Internship (FDA)

E-MAIL: Dickinson@uchicago.edu

WEB: http://dickinsonlab.uchicago.edu/

RESEARCH INTERESTS:

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.

 

Selected References:

Dickinson, B.C.; Packer, M.S.; Badran, A.H.; Liu, D.R. “A system for the continuous directed evolution of proteases rapidly reveals drug-resistance mutations.” Nat. Commun., 2014, 5, 5352.

Dickinson, B.C.; Leconte, A.M.; Allen, B.; Esvelt, K.M.; Liu, D.R.L. "Experimental interrogation of the path dependence and stochasticity of protein evolution using phage-assisted continuous evolution.“ Proc. Natl. Acad. Sci. USA. 2013, 110, 9007-9012.

Leconte, A.M.; Dickinson, B.C.; Yang, D.D.; Chen, I.A.; Allen, B.; Liu, D.R.L. "A population-based experimental model for protein evolution: Effects of mutation rate and selection stringency on evolutionary outcomes.“ Biochemistry. 2013, 52, 1490-1499.

Dickinson, B.C.; Lin, V.S.; Chang. C.J. "Preparation and use of MitoPY1 imaging hydrogen peroxide in mitochondria of live cells.“ Nat. Prot. 2013, 8, 1249-1259.

Dickinson, B.C.; Tang, Y.; Chang, Z.; Chang, C.J. "A nuclear-localized fluorescent hydrogen peroxide probe for monitoring sirtuin-mediated oxidative stress responses in vivo." Chem. Biol. 2011, 18, 943-948.

Dickinson, B.C.; Chang, C.J. "Chemistry and biology of reactive oxygen species in signaling or stress responses." Nat. Chem. Biol. 2011, 7, 504-511.

Dickinson, B.C.; Peltier, J.; Stone, D.; Schaffer, D.V.; Chang, C.J. “Nox2 redox signaling maintains essential cell populations in the brain.” Nat. Chem. Biol. 2011, 7, 106-112.

Miller, E.W.; Dickinson, B.C.; Chang, C.J. “Aquaporin-3 mediates hydrogen peroxide uptake to regulate downstream intracellular signaling.” Proc. Natl. Acad. Sci. USA. 2010, 107, 15681-15686.

Dickinson, B.C.; Huynh, C.; Chang, C.J. “A palette of fluorescent probes with varying emission colors for imaging hydrogen peroxide signaling in living cells.” J. Am. Chem. Soc. 2010, 132, 5906–5915.

Dickinson, B.C.; Srikun, D.; Chang, C.J. “Mitochondrial-targeted fluorescent probes for reactive oxygen species.” Curr. Opin. Chem. Biol. 2010, 14, 50–56.