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Prof. Devaraj focuses on the design of chemoselective reactions for addressing problems in bottom-up synthetic biology and molecular imaging. Bioconjugation chemistries are some of the most important and commonly used tools in chemical biology. His interdisciplinary research aims to advance important knowledge in chemical biology by extending the use of bioconjugation reactions into previously unexplored frontiers and challenging preconceived notions of where chemical reactions can be performed. A few representative research thrusts are summarized below.
Synthesis of Artificial Membranes
Natural cells have a number of mechanisms to organize biochemical pathways, one of the most prominent being membrane compartmentalization. All living cells utilize membranes to define physical boundaries, control transport, and perform signal transduction. We are devleoping and exploring novel reactions that can trigger de novo vesicle formation and reproduction. While many of the reactions we study are not prebiotically plausible, we believe such studies could reveal some of the fundamental chemical principles that led to the origin of life. Furthermore, we are studying how such reactions could improve our ability to study membrane localized structures and processes.
Tools for Detecting and Labeling RNA
One of the major revelations of the Human Genome Project was that protein coding genes comprise only 1.2% of the 3 billion base pairs of the human genome. In contrast, 75% of the genome is transcribed, and most of these transcripts do not code for proteins and are thus classified as noncoding RNAs (ncRNAs). Improved tools for the isolation and imaging of endogenous RNA, and associated protein partners, have the potential to illuminate the various functions and mechanisms of RNA, particularly the vast repertoire of ncRNA elements. Our lab at UCSD has begun developing chemical tools to aid in the imaging and manipulation of RNA. We are approaching this problem by exploiting novel enzymatic and non-enzymatic bioconjugation chemistries.
Tetrazine Bioorthogonal Reactions
We have had a long-standing interest in the advancement and application of tetrazine cycloadditions, a form of next generation “click” chemistry, to bioconjugation problems. Our goal is to advance the synthetic knowledge related to this unique class of inverse electron demand Diels-Alder cycloadditions to create novel tools for chemical biology research. Tetrazine reactions are attractive because they proceed in the absence of catalysts, have rapid reaction kinetics, and are compatible with fluorogenic probes for live cell imaging. At UCSD, we are tackling many of the challenges in the field. For instance, we are expanding the synthetic methods available to generate tetrazines and are exploring new dienophiles such as cyclopropenes and benzonorbornadienes. We are actively translating our chemical advances to applications in imaging and diagnostics.
Neal Devaraj is an Associate Professor of Chemistry and Biochemistry at the University of California, San Diego (UCSD). A native of Southern California, he attended college at the Massachusetts Institute of Technology where he performed research in the lab of Prof. Moungi Bawendi. He earned his PhD in Chemistry at Stanford University in the labs of Profs. James Collman and Christopher Chidsey. After a postdoctoral fellowship at the Harvard Medical School in the lab of Prof. Ralph Weissleder, he joined UCSD. His research interests are in bioconjugation, chemical biology, and bottom-up synthetic biology. Recent awards for Prof. Devaraj are the 2017 ACS Award in Pure Chemistry, 2016 NIH Pathfinder Award, the 2016 National Fresenius Award and the 2016 Camille Dreyfus Teacher-Scholar Award.