Our Publications

Note that plasmid reagents from the Savage Lab are available from our addgene site and that all source code from our work is available on our github site. 

2024

Prywes N, Philips NR, Oltrogge LM, Lindner S, Tsai YCC, de Pins B, Cowan AE, Taylor-Kearney LJ, Chang HA, Hall LN, Bellieny-Rabelo D, Nisonoff HM, Weissman RF, Flamholz AI, Ding D, Bhatt AY, Shih PM, Mueller-Cajar O, Milo R, Savage DF. A map of the rubisco biochemical landscape. bioRxiv. 2024. Link 

Valentin-Alvarado LE, Shi LD, Appler KE, Crits-Christoph A, Cui M, De Anda V, Leão P, Adler BA, Roberts RJ, Sachdeva R, Baker BJ, Savage DF, Banfield JF. Genetic elements and defense systems drive diversification and evolution in Asgard archaea. bioRxiv. 2024. Link

Panich J, Toppari E, Tejedor-Sanz S, Fong B, Dugan E, Chen Y, Petzold CJ, Zhao Z, Yoshikuni Y, Savage DF, Singer SW. Functional plasticity of HCO3- uptake and CO2 fixation in Cupriavidus necator H16. Bioresour Technol. Elsevier BV; 2024 Oct 1;410(131214):131214. Link

Valentin-Alvarado LE, Appler KE, De Anda V, Schoelmerich MC, West-Roberts J, Kivenson V, Crits-Christoph A, Ly L, Sachdeva R, Greening C, Savage DF, Baker BJ, Banfield JF. Asgard archaea modulate potential methanogenesis substrates in wetland soil. Nat Commun. 2024 Jul 31;15(1):6384. Link

Valentin-Alvarado LE, Fakra SC, Probst AJ, Giska JR, Jaffe AL, Oltrogge LM, West-Roberts J, Rowland J, Manga M, Savage DF, Greening C, Baker BJ, Banfield JF. Autotrophic biofilms sustained by deeply sourced groundwater host diverse bacteria implicated in sulfur and hydrogen metabolism. Microbiome. BioMed Central; 2024 Jan 26;12(1):15. Link

Ding D, Shaw AY, Sinai S, Rollins N, Prywes N, Savage DF, Laub MT, Marks DS. Protein design using structure-based residue preferences. Nat Commun. 2024 Feb 22;15(1):1639. Link

Turnsek JB, Oltrogge LM, Savage DF. Conserved and repetitive motifs in an intrinsically disordered protein drive ⍺-carboxysome assembly. J Biol Chem. Elsevier BV; 2024 Jul 4;(107532):107532. Link

Soni C, Prywes N, Hall M, Nair MA, Savage DF, Schepartz A, Chatterjee A. A translation-independent directed evolution strategy to engineer aminoacyl-tRNA synthetases. ACS Cent Sci. American Chemical Society (ACS); 2024 Jun 26;10(6):1211–1220. Link

Oltrogge LM, Chen AW, Chaijarasphong T, Turnšek JB, Savage DF. 2024. α-Carboxysome Size Is Controlled by the Disordered Scaffold Protein CsoS2. Biochemistry 63: 219–229. Link

2023

Blikstad C, Dugan EJ, Laughlin TG, Turnšek JB, Liu MD, Shoemaker SR, Vogiatzi N, Remis JP, Savage DF. 2023. Identification of a carbonic anhydrase-Rubisco complex within the alpha-carboxysome. Proc Natl Acad Sci U S A 120: e2308600120. Link

Armbruster EG, Lee J, Hutchings J, VanderWal AR, Enustun E, Adler BA, Aindow A, Deep A, Rodriguez ZK, Morgan CJ, et al. 2023. Sequential membrane- and protein-bound organelles compartmentalize genomes during phage infection. bioRxiv. Link

Adler BA, Al-Shimary MJ, Patel JR, Armbruster E, Colognori D, Charles EJ, Miller KV, Lahiri A, Trinidad M, Boger R, et al. 2023. Genome-wide Characterization of Diverse Bacteriophages Enabled by RNA-Binding CRISPRi. bioRxiv 2023.09.18.558157. Link

Adler BA, Trinidad MI, Bellieny-Rabelo D, Zhang E, Karp HM, Skopintsev P, Thornton BW, Weissman RF, Yoon PH, Chen L, et al. 2023. CasPEDIA Database: a functional classification system for class 2 CRISPR-Cas enzymes. Nucleic Acids Res. Link

Prywes N, Phillips NR, Tuck OT, Valentin-Alvarado LE, Savage DF. 2023. Rubisco Function, Evolution, and Engineering. Annu Rev Biochem 92: 385–410. Link

Wang RZ, Nichols RJ, Liu AK, Flamholz AI, Artier J, Banda DM, Savage DF, Eiler JM, Shih PM, Fischer WW. 2023. Carbon isotope fractionation by an ancestral rubisco suggests that biological proxies for CO2 through geologic time should be reevaluated. Proc Natl Acad Sci U S A 120: e2300466120. Link

Stahl EC, Sabo JK, Kang MH, Allen R, Applegate E, Kim SE, Kwon Y, Seth A, Lemus N, Salinas-Rios V, et al. 2023. Genome editing in the mouse brain with minimally immunogenic Cas9 RNPs. Mol Ther 31: 2422–2438. Link

2022

Lavania AA, Carpenter WB, Oltrogge LM, Perez D, Turnšek JB, Savage DF, Moerner WE. 2022. Exploring Masses and Internal Mass Distributions of Single Carboxysomes in Free Solution Using Fluorescence and Interferometric Scattering in an Anti-Brownian Trap. J Phys Chem B 126: 8747–8759. Link

Flamholz AI, Dugan E, Panich J, Desmarais JJ, Oltrogge LM, Fischer WW, Singer SW, Savage DF. 2022. Trajectories for the evolution of bacterial CO2-concentrating mechanisms. Proc Natl Acad Sci U S A 119: e2210539119. Link

Al-Shayeb B, Skopintsev P, Soczek KM, Stahl EC, Li Z, Groover E, Smock D, Eggers AR, Pausch P, Cress BF, et al. 2022. Diverse virus-encoded CRISPR-Cas systems include streamlined genome editors. Cell 185: 4574–4586.e16. Link

Chandrasekaran SS, Agrawal S, Fanton A, Jangid AR, Charrez B, Escajeda AM, Son S, Mcintosh R, Tran H, Bhuiya A, et al. 2022. Rapid detection of SARS-CoV-2 RNA in saliva via Cas13. Nat Biomed Eng 6: 944–956. Link

Metskas LA, Ortega D, Oltrogge LM, Blikstad C, Lovejoy DR, Laughlin TG, Savage DF, Jensen GJ. 2022. Rubisco forms a lattice inside alpha-carboxysomes. Nat Commun 13: 4863. Link

Carpenter WB, Lavania AA, Borden JS, Oltrogge LM, Perez D, Dahlberg PD, Savage DF, Moerner WE. 2022. Ratiometric Sensing of Redox Environments Inside Individual Carboxysomes Trapped in Solution. J Phys Chem Lett 13: 4455–4462.

Perier C, Nasinghe E, Charles I, Ssetaba LJ, Ahyong V, Bangs D, Beatty PR, Czudnochowski N, Diallo A, Dugan E, et al. 2022. Workshop-based learning and networking: a scalable model for research capacity strengthening in low- and middle-income countries. Glob Health Action 15: 2062175.

2021

Charles EJ, Kim SE, Knott GJ, Smock D, Doudna J, Savage DF. 2021. Engineering improved Cas13 effectors for targeted post-transcriptional regulation of gene expression. bioRxiv 2021.05.26.445687.

LaFrance BJ, Cassidy-Amstutz C, Nichols RJ, Oltrogge LM, Nogales E, Savage DF. 2021. The encapsulin from Thermotoga maritima is a flavoprotein with a symmetry matched ferritin-like cargo protein. Sci Rep 11: 22810.

Liu TY, Knott GJ, Smock DCJ, Desmarais JJ, Son S, Bhuiya A, Jakhanwal S, Prywes N, Agrawal S, Díaz de León Derby M, et al. 2021. Accelerated RNA detection using tandem CRISPR nucleases. Nat Chem Biol 17: 982–988.

Nichols RJ, LaFrance B, Phillips NR, Radford DR, Oltrogge LM, Valentin-Alvarado LE, Bischoff AJ, Nogales E, Savage, DF. Discovery and characterization of a novel family of prokaryotic nanocompartments involved in sulfur metabolism. eLife 2021;10. Link

Borden JS, Savage DF. New discoveries expand possibilities for carboxysome engineering. Curr Opin Microbiol 2021; 61:58–66. Link

Shams, A., Higgins, S.A., Fellmann, C., Laughlin, T.J., Oakes, B.L., Lew, R., Lukarska, M., Arnold, M., Staahl, B., Doudna, J.A., Savage, D.F., 2020. Comprehensive deletion landscape of CRISPR-Cas9 identifies minimal RNA-guided DNA-binding modules. BioRxiv. Link *Science Magazine highlight

Lien KA, Dinshaw K, Nichols RJ, Cassidy-Amstutz C, Knight M, Singh R, Eltis LD, Savage DF, Stanley SA. 2021. A nanocompartment system contributes to defense against oxidative stress in Mycobacterium tuberculosis. Elife 10. Link

2020

Flamholz, A.I., Dugan, E., Blikstad, C., Gleizer, S., Ben-Nissan, R., Amram, S., Antonovsky, N., Ravishankar, S., Noor, E., Bar-Even, A., Milo, R., Savage, D.F., 2020. Functional reconstitution of a bacterial CO2 concentrating mechanism in E. coli. eLife 9. Link *Nature research highlight *Innovative Genomics Institute highlight

Oltrogge LM, Chaijarasphong T, Chen AW, Bolin ER, Marqusee S, Savage DF. 2020. Multivalent interactions between CsoS2 and Rubisco mediate α-carboxysome formation. Nat Struct Mol Biol 27: 281–287. Link

Laughlin, TG, Savage, DF, Davies, KM, 2020. Recent advances on the structure and function of NDH-1: The complex I of oxygenic photosynthesis. Biochim. Biophys. Acta Bioenerg. 148254. Link 

Lee T-H, Carpenter TS, D’haeseleer P, Savage DF, Yung MC. 2020. Encapsulin carrier proteins for enhanced expression of antimicrobial peptides. Biotechnol Bioeng 117: 603– 613.

2019

Lee T-H, Carpenter TS, D’haeseleer P, Savage DF, Yung MC. 2019. Encapsulin carrier proteins for enhanced expression of antimicrobial peptides. Biotechnol Bioeng. Link

Oltrogge LM, Chaijarasphong T, Chen AW, Bolin ER, Marqusee S, Savage DF. 2019. alpha-carboxysome formation is mediated by the multivalent and disordered protein CsoS2. BioRxiv. DOI: 10.1101/708164.

Desmarais JJ, Flamholz AI, Blikstad C, Dugan EJ, Laughlin TG, Oltrogge LM, Chen AW, Wetmore K, Diamond S, Wang JY, et al. 2019. DABs are inorganic carbon pumps found throughout prokaryotic phyla. Nat Microbiol. 4: 2204-2215. Link

Flamholz AI, Prywes N, Moran U, Davidi D, Bar-On YM, Oltrogge LM, Alves R, Savage D, Milo R. 2019. Revisiting Trade-offs between Rubisco Kinetic Parameters. Biochemistry. 58: 3365-3376. Link

Huang TP, Zhao KT, Miller SM, Gaudelli NM, Oakes BL, Fellmann C, Savage DF, Liu DR. 2019. Circularly permuted and PAM-modified Cas9 variants broaden the targeting scope of base editors. Nat Biotechnol 37: 626–631. Link

Harper CC, Elliott AG, Oltrogge LM, Savage DF, Williams ER. 2019. Multiplexed Charge Detection Mass Spectrometry for High-Throughput Single Ion Analysis of Large Molecules. Anal Chem 91: 7458 - 7465. Link

Blikstad C, Flamholz AI, Oltrogge LM, Savage DF. 2019. Learning to Build a β-Carboxysome. Biochemistry 58: 2091–2092. Link

Laughlin TG, Bayne AN, Trempe J-F, Savage DF, Davies KM. 2019. Structure of the complex I-like molecule NDH of oxygenic photosynthesis. Nature 566: 411–414. Link

Oakes BL, Fellmann C, Rishi H, Taylor KL, Ren SM, Nadler DC, Yokoo R, Arkin AP, Doudna JA, Savage DF. 2019. CRISPR-Cas9 Circular Permutants as Programmable Scaffolds for Genome Modification. Cell 176: 254–267.e16. Link

2018

Flamholz A, Prywes N, Moran U, Davidi D, Bar-On Y, Oltrogge L, Alves R, Savage D, Milo R. 2018. Revisiting tradeoffs in Rubisco kinetic parameters. bioRxiv 470021. Link

Desmarais JJ, Flamholz AI, Blikstad C, Dugan EJ, Laughlin TG, Oltrogge LM, Chen AW, Wetmore K, Diamond S, Wang JY, Savage DF. 2018. Genome-wide screening reveals a novel class of carbonic anhydrase-like inorganic carbon transporters in chemoautotrophic bacteria. bioRxiv 476713. Link

Kundert K, Lucas JE, Watters KE, Fellmann C, Ng AN, Heineike BM, Fitzsimmons CM, Oakes BL, Savage DF, El-Samad H, Doudna JA, Kortemme T. Controlling CRISPR-Cas9 with ligand-activated and ligand-deactivated sgRNAs. bioRxiv, 323105. Link

Welkie DG, Rubin BE, Diamond S, Hood RD, Savage DF, Golden SS. 2018. A Hard Day's Night: Cyanobacteria in Diel Cycles. Trends in Microbiology. Link

Chaijarasphong T, Savage DF. 2018. Sequestered: Design and Construction of Synthetic Organelles. Synthetic Biology: Parts, Devices and Applications 8.

Higgins SA, Savage DF. 2018. Protein Science by DNA Sequencing: How Advances in Molecular Biology Are Accelerating Biochemistry. Biochemistry 57: 38–46. Link

2017

Higgins SA, Savage DF. 2018. Protein Science by DNA Sequencing: How Advances in Molecular Biology Are Accelerating Biochemistry. Biochemistry 57: 38–46. Link

Higgins, SA, Ouonkap, R, Savage, DF. 2017. Rapid and Programmable Protein Mutagenesis Using Plasmid Recombineering. ACS Synth. Biol. DOI: 10.1021/acssynbio.7b00112 Link 

Nichols RJ*, Cassidy-Amstutz C*, Chaijarasphong T, Savage DF. Encapsulins: molecular biology of the shell. Crit. Rev. Biochem. Mol. Biol. 2017 Jun 21;:1–12.  *denote equal contribution Link 

2016

Savage D, Zhang W. 2016. Biofuels: At the crossroads. Current Opinion in Chemical Biology 35: A1–A3. Link

Morgan* S-A, Nadler* DC, Yokoo R, Savage DF. 2016. Biofuel metabolic engineering with biosensors. Current Opinion in Chemical Biology 35: 150–158. *denote equal contribution Link

Mangan NM*, Flamholz A*, Milo R, Savage DF. 2016. Efficient operation of the cyanobacterial CO2 concentrating mechanism depends strongly on pH.  PNAS. doi: 10.1073/pnas.1525145113. *denote equal contribution Link

Hood RD, Higgins S, Flamholz A, Nichols RJ, Savage DF. 2016. The stringent response regulates adaptation to darkness in a cyanobacterium. PNAS. doi:10.1073/pnas.1524915113. Link 

Gerhardt KP, Olson EJ, Castillo-Hair SM, Hartsough LA, Landry BP, Ekness F, Yokoo R, Gomez EJ, Ramakrishnan P, Suh J, et al. 2016. An open-hardware platform for optogenetics and photobiology. Sci Rep 6: 35363. Link 

Nadler DC*, Morgan SA*, Flamholz A, Kortright K, Savage DF. 2016. Rapid construction of metabolite biosensors using domain-insertion profiling. Nature Communications 10.1038/ncomms12266. *denote equal contribution Link 

Cassidy-Amstutz C, Oltrogge LM, Going CC, Lee A, Teng PK, Quintanilla D, East-Seletsky A, Williams ER, Savage DF. 2016. Identification of a minimal peptide tag for in vivo and in vitro loading of encapsulin. Biochemistry. Link

Oakes BL, Nadler DC, Flamholz A, Fellmann C, Staahl BT, Doudna JA, Savage DF. 2016. Profiling of engineering hotspots identifies an allosteric CRISPR-Cas9 switch. Nat Biotechnol. Link

Chaijarasphong T, Nichols RJ, Kortright KE, Nixon CF, Teng PK, Oltrogge LM, Savage DF. 2016. Programmed Ribosomal Frameshifting Mediates Expression of the α-Carboxysome. J Mol Biol 428: 153–164. Link

2015

Yokoo R, Hood RD, Savage DF. 2015. Live-cell imaging of cyanobacteria. Photosynthesis Research 126: 33–46. Link

2014

Oakes BL, Nadler DC, Savage DF. 2014. Protein engineering of Cas9 for enhanced function. Methods in enzymology 546: 491–511. Link

2013

Chen AH, Robinson-Mosher A, Savage DF, Silver PA, Polka JK. 2013. The bacterial carbon-fixing organelle is formed by shell envelopment of preassembled cargo. PLoS ONE 8: e76127. Link

2012

Chen AH, Afonso B, Silver PA, Savage DF. 2012. Spatial and temporal organization of chromosome duplication and segregation in the cyanobacterium Synechococcus elongatus PCC 7942. PLoS ONE 7: e47837. Link

Bonacci W, Teng PK, Afonso B, Niederholtmeyer H, Grob P, Silver PA, Savage DF. 2012. Modularity of a carbon-fixing protein organelle. Proc Natl Acad Sci USA 109: 478–483. Link

2010

Niederholtmeyer H, Wolfstädter BT, Savage DF, Silver PA, Way JC. 2010. Engineering cyanobacteria to synthesize and export hydrophilic products. Appl Environ Microbiol 76: 3462–3466. Link

Savage DF*, Afonso B*, Chen AH, Silver PA. 2010. Spatially ordered dynamics of the bacterial carbon fixation machinery. Science 327: 1258–1261. *denote equal contribution Link

older work from Savage et alia

Structural context shapes the aquaporin selectivity filter. Savage, D.F., O’Connell III, J.D., Stroud R.M. (2010) PNAS. 107:17164-9. 

A general protocol for the crystallization of membrane proteins for X-ray structural investi gation. Newby, Z.E., O'Connell 3rd, J.D., Gruswitz, F., Hays, F.A., Harries, W.E., Harwood, I.M., Ho, J.D., Lee, J.K., Savage, D.F., Miercke, L.J., Stroud, R.M. (2009) Nat Protoc. 4:619-37. 

Defossiling fuel: How synthetic biology can transform biofuel production. Savage, D.F., Way, J., Silver, P.A. (2008) ACS Chem. Biol. 3:13-6. 

Structural basis of aquaporin inhibition by mercury. Savage, D.F. and Stroud, R.M. (2007) J. Mol. Biol. 368: 607-17. 

Cell-free complements in vivo expression of the E. coli membrane proteome. Savage, D.F., Anderson C.L, Robles-Colmenares, Y., Newby, Z.A., Stroud R.M. (2007) Protein Sci. 16:966-76. 

Substrate twinning activates the signal recognition particle and its receptor. Egea P.F., Shan S.O., Napetschnig J., Savage D.F., Walter P., Stroud R.M. (2004) Nature, 426:215-221.

Water and glycerol permeation through the glycerol channel GlpF and the aquaporin family. Lee, J.K., Khademi, S., Harries, W., Savage, D., Miercke, L, Stroud, R.M. (2004) J. Synchrotron Radiat. 11:86-88

Architecture and selectivity in aquaporins: 2.5Å x-ray structure of aquaporin Z. Savage, D. F., Egea, P.F., Robles, Y.C., O’Connell III, J.D., and Stroud, R.M. (2003) PLoS Biology, 1:334-340. 

Selectivity and conductance among the glycerol and water conducting aquaporin family of channels. Stroud, R.M., Savage, D.F., Miercke, L.J., Lee, J.K., Khademi, S., Harries, W. (2003). FEBS Letters, 555:79-84. 

Catalysis, specificity, and ACP docking site of Streptomyces coelicolor malonyl-CoA: ACP transacylase. Keatinge-Clay, A.T., Shelat, A.A., Savage, D.F., Tsai, S.C., Miercke, L.J.W., O'Connell 3rd, J.D., Khosla, C., and Stroud, R.M. (2003) Structure, 11:147-154.