Biomimetic Chemistry, Molecular Imaging, Chemical Biology
Chemistry and Biology,
University of California, San Diego
University of California, San Diego
Awards and Academic Honors
ACS Award in Pure Chemistry
National Fresenius Award
Camille Dreyfus Teacher-Scholar Award
NSF CAREER Award
NIH Research Scientist Career Development Award
ACS Division of Inorganic Chemistry Young Investigator Award
Stanford Graduate Fellowship
MIT Department of Chemistry Alpha Chi Sigma Award
The Devaraj Lab at UCSD 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. Our 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.
Primary Research Area
My experience as an ethnic minority in this country has cemented my commitment to providing a diverse environment to my coworkers and students. Diversity has been an important component of both to my scientific career and my personal life. I am dedicated to encouraging equality, fairness, and diversity in the workplace. This commitment to promoting diversity is reflected in my recruitment, retention, and mentorship of several students and fellows from underrepresented backgrounds. Being able to improve access and training to students from underrepresented groups is truly exciting and, in my opinion, one of the greatest benefits of working at a top-tier public research university such as UCSD. My philosophy toward mentoring is to emphasize the excitement of science, the positives of a scientific career path, and the attainability of research goals given proper design and methodological execution.
I also work with UCSD CREATE (Center for Research on Educational Equity, Assessment, and Teaching Excellence) to develop an educational component integrating our bottom-up synthetic cell research with an existing coordinated effort at UC San Diego to improve the STEM pipeline K-20 in San Diego. In particular, we will focus on reaching populations typically underrepresented in STEM fields. Specifically, this coordinated effort will link our lab’s research interests and results in the chemistry of vesicle reproduction with two efforts at the university: 1) the San Diego Science Project (SDSP), a K-12 professional development and teacher support organization training both UCSD undergrads and teachers to engage science content with secondary students and 2) the TRIO Upward Bound Math/Science Program (UBMS), a federally funded outreach program that aims to increase the number of underrepresented minorities and low-income youth that enroll in undergraduate education. Our goal is to stimulate the entry of underrepresented and low income student populations into STEM fields and to expose a broad range of students and teachers to origin of life and synthetic biology topics.
a catalytic biomimetic coupling reaction capable of driving the de novo self-assembly of phospholipid membranes.
We have designed methyl-cyclopropene tags capable of reacting rapidly with tetrazines while maintaining stability in aqueous solution.
- Brea RJ,Rudd AK,Devaraj NK "Nonenzymatic biomimetic remodeling of phospholipids in synthetic liposomes.", Proc Natl Acad Sci U S A, 2016, Vol. 113, Issue 31, 8589-94
- Wu H,Alexander SC,Jin S,Devaraj NK "A Bioorthogonal Near-infrared Fluorogenic Probe for mRNA Detection.", J Am Chem Soc, 2016,
- Alexander SC, Busby KN, Cole CM, Zhou C, Devaraj NK "Site-Specific Covalent Labeling of RNA by Enzymatic Transglycosylation", J Am Chem Soc, 2015, Vol. 137, Issue 40, 12756-12759
- Cole CM, Brea RJ, Kim YH, Hardy MD, Yang J, Devaraj NK, "Spontaneous Reconstitution of Functional Transmembrane Proteins During Bioorthogonal Phospholipid Membrane Synthesis.", Angew Chem Int Ed Engl, 2015, Vol. 54, Issue 43, 12738-12742
- Ehret F, Wu H, Alexander SC, Devaraj NK, "Electrochemical Control of Rapid Bioorthogonal Tetrazine Ligations for Selective Functionalization of Microelectrodes.", J Am Chem Soc, 2015, Vol. 137, Issue 28, 8876-9
- Hardy MD, Yang J, Selimkhanov J, Cole CM, Tsimring LS, Devaraj NK, "Self-reproducing catalyst drives repeated phospholipid synthesis and membrane growth.", Proc Natl Acad Sci U S A, 2015, Vol. 112, Issue 27, 8187-92
- Rudd AK, Valls Cuevas JM, Devaraj NK, "SNAP-Tag-Reactive Lipid Anchors Enable Targeted and Spatiotemporally Controlled Localization of Proteins to Phospholipid Membranes.", J Am Chem Soc, 2015, Vol. 137, Issue 15, 4884-7
- Brea RJ, Cole CM, Devaraj NK, "In situ vesicle formation by native chemical ligation.", Angew Chem Int Ed Engl, 2014, Vol. 53, Issue 51, 14102-5
- Wu H, Cisneros BT, Cole CM, Devaraj NK, "Bioorthogonal Tetrazine-Mediated Transfer Reactions Facilitate Reaction Turnover in Nucleic Acid-Templated Detection of MicroRNA.", J Am Chem Soc, 2014, Vol. 136, Issue 52, 17942-5
- Wu H, Yang J, Šečkutė J, Devaraj NK, "In situ synthesis of alkenyl tetrazines for highly fluorogenic bioorthogonal live-cell imaging probes.", Angew Chem Int Ed Engl, 2014, Vol. 53, Issue 23, 5805-9
- Budin I, Devaraj NK, "Membrane assembly driven by a biomimetic coupling reaction.", J Am Chem Soc, 2012, Vol. 134, Issue 2, 751-3
- Yang J, Karver MR, Li W, Sahu S, Devaraj NK, "Metal-catalyzed one-pot synthesis of tetrazines directly from aliphatic nitriles and hydrazine.", Angew Chem Int Ed Engl, 2012, Vol. 51, Issue 21, 5222-5
- Yang J, Šečkutė J, Cole CM, Devaraj NK, "Live-cell imaging of cyclopropene tags with fluorogenic tetrazine cycloadditions.", Angew Chem Int Ed Engl, 2012, Vol. 51, Issue 30, 7476-9