Rice University
BioSciences at Rice

Jonathan Silberg

Professor of BioSciences

silberg_figure

Our research is focused on understanding the organizing principles of life through bottom-up synthetic biology. We are developing strategies to reliably design cellular programs with robust characteristics that allow for applications in agriculture, biogeochemical cycling, ecology, electronics, energy, information storage, and medicine. Our research falls into three major areas: (1) Environmental Synthetic Biology. We are using synthetic biology to study microbial behaviors in hard-to-image soils and sediments where traditional visual reporters are challenging to use. The goal of these studies is to understand how changes in the physical and chemical properties of a matrix control dynamic microbial behaviors, like quorum sensing, horizontal gene transfer, and microbe-plant signaling that underlies the formation symbiosis. To facilitate studies in soils and sediments, we are developing new outputs for genetic circuits (gas reporters) that provide dynamic information on gene expression in non-transparent materials. (2) Redox Synthetic Biology. We are using synthetic electron transport pathways to study the electron transfer mediated by small protein electron carriers like ferredoxins. These studies are motivated by our interest in understanding what controls the proportion of electrons that are transferred between different metabolic pathways with a long-term goal of deriving maps for electron flux in cells, i.e., the electron fluxome. Using the knowledge that we glean from these studies, we are building synthetic electron transfer pathways and cell-electronic devices (bioelectronics) to assist with fundamental studies and enable the creation of useful new technologies. (3) Overcoming Component Limitations in Biology. We have developed transposon mutagenesis methods that simplify the construction of combinatorial libraries encoding proteins, including libraries of fragmented and circularly permuted proteins. We are subjecting these libraries to selections, deep sequencing, and computational analysis to obtain unbiased insight into protein tolerance to these mutational lesions. In parallel, we are applying these methods to overcome component limitations in synthetic biology by creating protein switches that display novel chemical-dependent activities.


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Cheng, H.Y., Del Valle, I., Gao, X., Masiello, C.A., Bennett, G.N., and Silberg,J.J., Ratiometric gas reporting: a non-disruptive approach to monitor gene expression in soils.  ACS Synth. Biol. 2017

Atkinson, J.A., Jones, A.J., Zhou, Q., and Silberg, J.J., Circular permutation profiling by deep sequencing libraries created using transposon mutagenesis.   2017

Jones, A.J., Atkinson, J.A., and Silberg, J.J., PERmutation Using Transposase Engineering (PERMUTE): a simple approach for constructing circularly permuted protein libraries.  Methods in Molecular Biology, (A. Reeves, Ed.), 1498 2017: 295-308

Stubbs, B. Poster Presentation, Speakers Spotlight Rice Research Opportunities.  San Jacinto Times 2017

Thomas, E.E., Pandey, N., Knudsen, S., Ball, Z, and Silberg, J.J, Programming post-translational control over the metabolic labeling of cellularproteins with a non-canonical amino acid.  ACS Synth. Biol., 6(8) 2017: 1572-1582

Williams, M. Protein ‘spy’ gains new abilities.  Rice News 2017

Atkinson, J.A., Campbell, I.J., Bennett, G.N., and Silberg, J.J., Cellular assays for ferredoxins: a strategy to understand electron flow through protein carriers that link metabolic pathways.  Biochemistry, 55(51) 2016: 7047–7064

Gao, X., Cheng, H.Y., Del Valle, I., Liu, S., Masiello, C.A., and Silberg, J.J., Charcoal disrupts soil microbial communication through a combination of sorption and hydrolysis.   ACS Omega, 1(2) 2016: 226-233

Boyd, J. Rice introduces iBIO initiative.  Rice News 2016

Jones AJ, Mehta MM, Thomas EE, Atkinson JT, Segall-Shapiro TH, Liu S, Silberg JJ, The structure of a thermophilic kinase shapes fitness upon random circular permutation.  ACS Synth Biol., 5(5) 2016: 415-25

Pandey N, Kuypers BE, Nassif B, Thomas EE, Alnahhas RN, Segatori L, Silberg JJ, Tolerance of a knotted near infrared fluorescent protein to random circular permutation..  Biochemistry, 55(27) 2016: 3763-73

Cheng, H.Y., Masiello, C.A., Bennett, G.N., and Silberg, J.J., Volatile gas production by methyl halide transferase: an in situreporter of microbial gene expression in soil.  Environ. Sci. Technol., 50(16) 2016: 8750-9

Pandey, N., Nobles, C., Zechiedrich, L., Maresso, A.W., and Silberg, J.J. Combining random gene fission and rational gene fusion to discover near-infrared fluorescent protein fragments that report on protein-protein interactions.  ACS Synth. Biol. 2014

Zhao, W., Bonem, M., McWhite, C., Silberg, J.J., and Segatori, L. The Deg-On system: a mammalian synthetic gene circuit to quantify proteasomal degradation.  Nature Communications, 5 2014: 3612

Judd, J., Ho, M.L., Tiwari, A., Gomez, E.J., Dempsey, C., Van Vliet, K., Igoshin, O., Silberg, J.J., Agbandje-McKenna, M., and Suh, J. Tunable virus nanonodes programmed to compute proteolytic signatures.  ACS Nano, 8 2014: 4740-4746

Mahdavi, A., Segall-Shapiro, T.H., Kou, S., Jindal, G.A., Hoff, K.G., Liu, S., Chitsaz, M., Ismagilov, J.J., Silberg, J.J., and Tirrell, D.A. A genetic AND gate for selective interrogation of cellular protein synthesis.  JACS, 135 2013: 2979-2982

Masiello, C.A., Ye, C., Gao, G., Liu, S., Cheng, H.Y., Bennett, M.R., Rudgers, J.A., Wagner, D.S., Zygourakis, K., and Silberg, J.J. Biochar and microbial signaling: production conditions determine effects on microbial communication.  Environ. Sci. Technol. , 47 2013: 11496-11503

LeCroy, C., Masiello, C.A., Rudgers, J.A., Hockaday, W.C., and Silberg, J.J. Nitrogen, biochar, and mycorrhizae: Alteration of the symbiosis and oxidation of the char surface.  Soil Biology and Biochemistry, 58 2013: 248-254

Ho, M.L., Adler, B., Torre, M., Silberg, J.J., and Suh, J. SCHEMA computational design of virus capsid chimeras: calibrating how DNA packaging, protection, and transduction correlate with calculated disruption.  ACS Synth. Biol., 2 2013: 724-733

Mehta, M, Liu, S., and Silberg, J.J. A transposase strategy for creating libraries of circularly permuted proteins.  Nucleic Acids Research, 40(9) 2012: e71

Judd, J., Wei, F., Nguyen, P.Q., Tartaglia, L. J., Agbandje-McKenna, M., Silberg, J.J., and Suh, J. Random insertion of mCherry into the VP3 domain of adeno-associated virus (AAV) yields fluorescent capsids with no loss of infectivity.  Molecular Therapy – Nucleic Acids, 1 2012: e1

Vu, M, Zhai, P., Lee, J, Guerra, C., Liu, S., Gustin, M.C., and Silberg, J.J. The DNLZ/HEP zinc-binding domain is critical for regulation of the mitochondrial chaperone HSPA9.  Protein Science, 21 2012: 258-267

Zhai, P., Vu, M.T., Hoff, K.G., and Silberg, J.J. A conserved histidine in human DNLZ/HEP is required for stimulation of HSPA9 ATPase activity.  Biochem. Biophys. Res. Comm. , 408 2011: 589-594

Segall-Shapiro, T.H., Nguyen, P.Q., Dos Santos, E., Subedi, S., Suh, J., and Silberg, J.J. Mesophilic and hyperthermophilic adenylate kinases differ in their tolerance to random fragmentation.  J. Mol. Biol., 406 2011: 135-148

McGuire, R.M., Silberg, J.J., Pereira, F.A., and Raphael, R.M. Selective cell-surface labeling of the molecular motor prestin.  Biochem. Biophys. Res. Comm. , 410 2011: 134-139

Nguyen, P.Q. and Silberg, J.J. A selection for detecting protein-protein interactions within a thermophilic bacterium.  Prot. Eng. Des. & Sel., 23 2010: 529-536

Silberg, J.J., Nguyen, P.Q., and Stevenson, T. Computational design of chimeric protein libraries for directed evolution.  Methods in Molecular Biology: Topics in Computational Biology , 673 2010: 175-188

Hoff, K.G., Li, R., Goodlitt, R., Smolke, C. D., and Silberg, J.J., Fluorescence detection of protein-bound 2Fe2S clusters.  ChemBioChem, 10 2009: 667-670

Hoff, K.G., Culler, S. J., Nguyen, P. Q., McGuire, R.M., Silberg, J. J., and Smolke, C. D. In vivo fluorescent detection of Fe-S clusters coordinated by human GRX2.  Chemistry & Biology, 16 2009: 1299-1308

Silberg, J.J., and Nguyen, P.Q. Models predicting optimized strategies for protein evolution.  The Metabolic Pathway Engineering Handbook , 2 2009

Zhai, P., Stanworth, C., Liu, S., and Silberg, J.J. The human hsp70 escort protein Hep binds to the ATPase domain of mitochondrial Hsp70 and regulates nucleotide hydrolysis.  J. Biol. Chem., 283 2008: 26098-26106

Nguyen, P.Q., Liu, S., Thompson, J., and Silberg, J.J. Thermostability promotes the cooperative function of adenylate kinase fragments..  Prot. Eng. Des. Sel., 21 2008: 303-310

Drummond, D.A., Silberg, J.J., Wilke, C.O., Meyer, M.M., and Arnold, F.H. On the conservative nature of intragenic recombination.  Proc. Nat'l. Acad. Sci. U.S.A., 102 2005: 5380-5385

Bloom, J.D., Silberg, J.J., Wilke, C., Drummond, D.A., Adami, C., and Arnold, F.H. Thermodynamic prediction of protein neutrality.  Proc. Nat'l. Acad. Sci. U.S.A., 102 2005: 606-611

Cupp-Vickery, J.R., Silberg, J.J., Ta, D.T., and Vickery, L.E. Crystal structure of IscA, an iron-sulfur cluster assembly protein from Escherichia coli.  J. Mol. Biol., 338 2004: 127-137

Otey, C., Silberg, J.J., Endelman, J.B., Bandara, G., Voigt, C.A., and Arnold, F.H. Functional evolution and structural conservation in chimeric cytochromes P450: Calibrating a structure-guided approach.  Chemistry & Biology, 11 2004: 309-318

Endelman, J.B., Silberg, J.J., Wang, Z.G., and Arnold, F.H. Protein chimera library design as a shortest-path problem.  Prot. Eng. Des. & Sel., 17 2004: 589-594

Silberg, J.J., Tapley, T.L., Hoff, K.G., and Vickery, L.E. Regulation of the Hsc66 ATPase reaction cycle by the J-type cochaperone Hsc20 and the iron-sulfur escort protein IscU.  J. Biol. Chem., 279 2004: 53924-53931

Meyer, M.M., Silberg, J.J., Voigt, C.A., Endelman, J.B., Mayo, S.L., Wang, Z.G., and Arnold, F.H. Library analysis of SCHEMA-guided recombination.  Protein Science, 12 2003: 1686-1693

Hoff, K.G., Ta, D., Tapley, T.L., Silberg, J.J., and Vickery, L.E. Hsc66 substrate specificity is directed towards a discrete region of the Fe/S template protein IscU.  J. Biol. Chem., 277 2002: 27353-27359

Silberg, J.J., Hoff, K.G., Tapley, T.L., and Vickery, L.E. The Fe/S-escort protein IscU behaves as a substrate for the molecular chaperone Hsc66 from Escherichia coli.  J. Biol. Chem., 276 2002: 1696-1700

Urbina, H.D., Silberg, J.J., Hoff, K.G., and Vickery, L.E. Transfer of sulfur from IscS to IscU during iron-sulfur cluster assembly.  J. Biol. Chem., 276 2001: 44521-44526

Hoff, K.G., Silberg, J.J., and Vickery, L.E. Interaction of the iron-sulfur cluster assembly protein IscU with the Hsc66/Hsc20 molecular chaperone system in Escherichia coli.  Proc. Nat'l. Acad. Sci. U.S.A., 97 2000: 7790-7795

Silberg, J.J., and Vickery, L.E. Kinetic characterization of the ATPase cycle of the molecular chaperone Hsc66 from Escherichia coli.  J. Biol. Chem., 275 2000: 7779-7786

Silberg Lab Website

  • B.S. Biology (1994) University of California Irvine
  • B.S. Chemistry (1994) University of California Irvine
  • Ph.D. Biology (2000) University of California Irvine
  • Department of Bioengineering
  • Institute of Biosciences and Bioengineering
  • Keck Center for Quantitative Biomedical Sciences
  • Systems, Synthetic, and Physical Biology
Research Areas
  • bioelectronics, environmental synthetic biology, redox synthetic biology
Contact Information
Email: joff@rice.edu
Phone: 713 348-3849
Office: Keck Hall, 209