Devaraj, Neal
Biomimetic Chemistry, Artificial Cells, Chemical Biology
Biomimetic Chemistry, Artificial Cells, Chemical Biology
Contact Information
Professor of Chemistry and Biochemistry
Murray Goodman Endowed Chair in Chemistry and Biochemistry
Section Chair, Biochemistry and Biophysics
Office: Natural Sciences Bldg 3328
Phone: 858-534-9539
Email: ndevaraj@ucsd.edu
Web: www.devarajgroup.com
Group: View group members
Murray Goodman Endowed Chair in Chemistry and Biochemistry
Section Chair, Biochemistry and Biophysics
Office: Natural Sciences Bldg 3328
Phone: 858-534-9539
Email: ndevaraj@ucsd.edu
Web: www.devarajgroup.com
Group: View group members
Education
2007 PhD, Chemistry, Stanford University
2002 Dual BS, Chemistry and Biology, MIT
2007 PhD, Chemistry, Stanford University
2002 Dual BS, Chemistry and Biology, MIT
Appointments
2023 Section Chair, Biochemistry and Biophysics, University of California, San Diego
2021 Murray Goodman Endowed Chair, University of California, San Diego
2020-2021 Russell F. Doolittle Faculty Scholar, University of California, San Diego
2018 Professor, University of California, San Diego
2016-2018 Associate Professor, University of California, San Diego
2011-2016 Assistant Professor, University of California, San Diego
2023 Section Chair, Biochemistry and Biophysics, University of California, San Diego
2021 Murray Goodman Endowed Chair, University of California, San Diego
2020-2021 Russell F. Doolittle Faculty Scholar, University of California, San Diego
2018 Professor, University of California, San Diego
2016-2018 Associate Professor, University of California, San Diego
2011-2016 Assistant Professor, University of California, San Diego
Awards and Academic Honors
2025
Arthur C. Cope Scholar Award
2024
Sessler Lectureship
2022
Vannevar Bush Faculty Fellowship
2022
Bioconjugate Chemistry Lectureship Award
2021
Tetrahedron Young Investigator Award
2019
Leo Hendrik Baekeland Award
2019
Guggenheim Fellowship
2019
Eli Lilly Award in Biological Chemistry
2018
Magomedov-Shcherbinina Memorial Prize
2018
Lattimer Faculty Research Fellow
2018
Denkewalter Lecturer
2018
Blavatnik National Laureate in Chemistry
2017
ACS Award in Pure Chemistry
2016
National Fresenius Award
2016
Camille Dreyfus Teacher-Scholar Award
2007
ACS Division of Inorganic Chemistry Young Investigator Award
2002
MIT Department of Chemistry Alpha Chi Sigma Award
Research Interests
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 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.
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 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
Biochemistry
Biochemistry
Interdisciplinary interests
Bioorganic
Cellular Biochemistry
Synthesis
Cellular Biochemistry
Synthesis
Outreach Activities
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.
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.
Image Gallery
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.
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.
Selected Publications
- Cho CJ,An T,Lai YC,Vázquez-Salazar A,Fracassi A,Brea RJ,Chen IA,Devaraj NK "Protocells by spontaneous reaction of cysteine with short-chain thioesters.", Nat Chem, 2024, [View]
- Harjung A,Fracassi A,Devaraj NK "Encoding extracellular modification of artificial cell membranes using engineered self-translocating proteins.", Nat Commun, 2024, Vol. 15, Issue 1, 9363 [View]
- Bhattacharya A,Tanwar L,Fracassi A,Brea RJ,Salvador-Castell M,Khanal S,Sinha SK,Devaraj NK "Chemoselective Esterification of Natural and Prebiotic 1,2-Amino Alcohol Amphiphiles in Water.", J Am Chem Soc, 2023, [View]
- Chen J,Brea RJ,Fracassi A,Cho CJ,Wong AM,Salvador-Castell M,Sinha SK,Budin I,Devaraj NK "Rapid Formation of Non-canonical Phospholipid Membranes by Chemoselective Amide-Forming Ligations with Hydroxylamines.", Angew Chem Int Ed Engl, 2023, e202311635 [View]
- Lee Y,Fracassi A,Devaraj NK "Light-Driven Membrane Assembly, Shape-Shifting, and Tissue Formation in Chemically Responsive Synthetic Cells.", J Am Chem Soc, 2023, Vol. 145, Issue 47, 25815-25823 [View]
- Tota EM,Devaraj NK "Site-Specific Covalent Labeling of DNA Substrates by an RNA Transglycosylase.", J Am Chem Soc, 2023, Vol. 145, Issue 14, 8099-8106 [View]
- Flores J,Brea RJ,Lamas A,Fracassi A,Salvador-Castell M,Xu C,Baiz CR,Sinha SK,Devaraj NK "Rapid and Sequential Dual Oxime Ligation Enables De Novo Formation of Functional Synthetic Membranes from Water-Soluble Precursors.", Angew Chem Int Ed Engl, 2022, Vol. 61, Issue 29, e202200549 [View]
- Liu L,Zhang D,Johnson M,Devaraj NK "Light-activated tetrazines enable precision live-cell bioorthogonal chemistry.", Nat Chem, 2022, [View]
- Zhang D,Liu L,Jin S,Tota E,Li Z,Piao X,Zhang X,Fu XD,Devaraj NK "Site-Specific and Enzymatic Cross-Linking of sgRNA Enables Wavelength-Selectable Photoactivated Control of CRISPR Gene Editing.", J Am Chem Soc, 2022, Vol. 144, Issue 10, 4487-4495 [View]
- Bhattacharya A,Cho CJ,Brea RJ,Devaraj NK "Expression of Fatty Acyl-CoA Ligase Drives One-Pot De Novo Synthesis of Membrane-Bound Vesicles in a Cell-Free Transcription-Translation System.", J Am Chem Soc, 2021, Vol. 143, Issue 29, 11235-11242 [View]
- Khanal S,Brea RJ,Burkart MD,Devaraj NK "Chemoenzymatic Generation of Phospholipid Membranes Mediated by Type I Fatty Acid Synthase.", J Am Chem Soc, 2021, Vol. 143, Issue 23, 8533-8537 [View]
- Bhattacharya A,Niederholtmeyer H,Podolsky KA,Bhattacharya R,Song JJ,Brea RJ,Tsai CH,Sinha SK,Devaraj NK "Lipid sponge droplets as programmable synthetic organelles.", Proc Natl Acad Sci U S A, 2020, [View]
- Jin S,Brea RJ,Rudd AK,Moon SP,Pratt MR,Devaraj NK "Traceless native chemical ligation of lipid-modified peptide surfactants by mixed micelle formation.", Nat Commun, 2020, Vol. 11, Issue 1, 2793 [View]
- Liu L, Zou Y, Bhattacharya A, Zhang D, Lang SQ, Houk KN, Devaraj NK "Enzyme-free synthesis of natural phospholipids in water", Nat Chem, 2020, [View]
- Rudd AK,Mittal N,Lim EW,Metallo CM,Devaraj NK "A Small Molecule Fluorogenic Probe for the Detection of Sphingosine in Living Cells.", J Am Chem Soc, 2020, [View]
- Bhattacharya A,Brea RJ,Niederholtmeyer H,Devaraj NK "A minimal biochemical route towards de novo formation of synthetic phospholipid membranes.", Nat Commun, 2019, Vol. 10, Issue 1, 300 [View]
- Brea RJ,Bhattacharya A,Bhattacharya R,Song J,Sinha S,Devaraj NK "Highly Stable Artificial Cells from Galactopyranose-Derived Single-Chain Amphiphiles.", J Am Chem Soc, 2018, [View]
- Niederholtmeyer H,Chaggan C,Devaraj NK "Communication and quorum sensing in non-living mimics of eukaryotic cells.", Nat Commun, 2018, Vol. 9, Issue 1, 5027 [View]
- Rudd AK,Brea RJ,Devaraj NK "Amphiphile-Mediated Depalmitoylation of Proteins in Living Cells.", J Am Chem Soc, 2018, [View]
- Rudd AK,Devaraj NK "Traceless synthesis of ceramides in living cells reveals saturation-dependent apoptotic effects.", Proc Natl Acad Sci U S A, 2018, Vol. 115, Issue 29, 7485-7490 [View]
- Seoane A,Brea RJ,Fuertes A,Podolsky KA,Devaraj NK "Biomimetic Generation and Remodeling of Phospholipid Membranes by Dynamic Imine Chemistry.", J Am Chem Soc, 2018, [View]
- Zhang D,Zhou CY,Busby KN,Alexander SC,Devaraj NK "Light-Activated Control of Translation by Enzymatic Covalent mRNA Labeling.", Angew Chem Int Ed Engl, 2018, [View]