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Richard W. Roberts

Professor of Chemistry, Chemical Engineering and Materials Science, and Molecular and Computational Biology.
Full Member, USC Norris Cancer Center

Peptide and Protein Engineering via mRNA Display

NIH and Alfred P. Sloan Foundation Postdoctoral Fellow 1993-97 Harvard Medical School/MGH
Ph.D. Biophysical Chemistry, Yale University, 1993
B.S. Chemistry, University of Kansas, 1987
Office: RTH 507
Phone: (213) 821-4132
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Research Focus


The Chemical Biology of Protein Synthesis.

Research in the Roberts lab focuses on the protein synthesis machinery both as a tool for polypeptide design and as a target that can be probed using chemical means. A key aspect of my lab's work is peptide and protein design using in vitro selection experiments. Toward this end, we use mRNA display, a technique the PI conceived and implemented to enable polypeptide design (see figure below). This approach allows the lab to create and sieve more than 10 trillion independent peptide or protein sequences for function, the most of any technique currently available. In applying any design approach, it is optimal if key issues, including affinity, specificity, diversity, structure, dynamics, and biological activity can be addressed in a principled way. The lab desires to execute a research program that tackles all of these issues.
Our passion is using the tools of chemistry to understand and control biological processes. We have applied our design approach to address biological control, molecular recognition, stability, and dynamics in RNA-peptide complexes, G proteins and G protein coupled receptors (GPCRs). In the future, our efforts should provide new tools for systems biology and leads for therapeutic development.
mRNA display
mRNA display
. An mRNA template (black line) covalently attached to puromycin is used to program an in vitro translation reaction. After protein synthesis, the puromycin enters the ribosome in cis to form a covalent mRNA-protein fusion.

We are also very interested to re-engineer the protein synthesis machinery to create unnatural mRNA display libraries. This project, a nanoscale engineering effort, works to merge the power of display selections with the flexibility of combinatorial chemistry. To do this, the lab has worked to extend mRNA display beyond the natural genetic code, in an effort to create new and richly diverse compositions of matter for ligand design, drug discovery, and beyond.
In conjunction with our re-engineering efforts, we have become intensely interested in thinking about the ribosome as a target for puromycin analogues. Our work began with efforts to understand the ribosome's substrate specificity. These efforts have also yielded unexpected and exciting new reagents that have enabled us to visualize protein synthesis in vivo in T-cells and neurons with spatial and temporal resolution.

Finally, the PI's intellectual interest in evolution and the origin of life has lead to work on a model for the origin of the ribosome and a proposal for how Darwinian evolution could have begun via coupling genome replication and cellular growth.

Overall, research in the Roberts lab bridges Chemistry, Biology, and Engineering with the goal of bringing new approaches to molecular design, systems biology, and therapeutics. We have pursued these goals in both formal and informal collaborations with other labs including (J. Alberola-Ila, S. Benzer, P. Bjorkman, D. Dougherty, B. Hay, E. Schuman, A. Varshavsky, A. H. Zewail, S. R. Sprang N. Strynadka, J. W. Szostak, and L. Jan).

Selected publications



    Jalali-Yazdi, F., Lai L.H.., Takahashi, T.T., Roberts, R.W., 2016. High-Throughput Measurement of Binding Kinetics by mRNA Display and Next-Generation Sequencing. Angewandte Chemie 128, 4075-4078. doi: 10.1002/anie.201600077 [PDF]


    Jalali-Yazdi, F., Takahashi, T.T., Roberts, R.W., 2015. General, Label-Free Method for Determining Kd and Ligand Concentration Simultaneously. Analytical Chemistry 87, 11755-11762. doi:10.1021/acs.analchem.5b03069. doi: 10.1021/acs.analchem.5b03069 [PDF]


    Jalali-Yazdi, F., Corbin, J.M., Takahashi, T.T., Roberts, R.W., 2014. Robust, Quantitative Analysis of Proteins using Peptide Immunoreagents, in Vitro Translation, and an Ultrasensitive Acoustic Resonant Sensor. Analytical Chemistry 86, 4715-4722. doi: 10.1021/ac500084d [PDF]

    Howell, S.M., Fiacco, S.V., Takahashi, T.T., Jalali-Yazdi, F., Millward, S.W., Hu, B., Wang, P., Roberts, R.W., 2014. Serum Stable Natural Peptides Designed by mRNA Display. Scientific Reports 4. doi: 10.1038/srep06008 [PDF]


    Xiao, L., Hung, K.-C., Takahashi, T.T., Joo, K.-I., Lim, M., Roberts, R.W., Wang, P., 2013. Antibody-Mimetic Ligand Selected by mRNA Display Targets DC-SIGN for Dendritic Cell-Directed Antigen Delivery. ACS chemical biology 8, 967-977. doi: 10.1021/cb300680c [PDF]

    Mora, R.J., Roberts, R.W., Arnold, D.B., 2013. Recombinant Probes Reveal Dynamic Localization of CaMKII alpha within Somata of Cortical Neurons. Journal of Neuroscience 33, 14579-14590. doi: 10.1523/JNEUROSCI.2108-13.2013.  [PDF]

    Gross, G.G., Junge, J.A., Mora, R.J., Kwon, H.-B., Olson, C.A., Takahashi, T.T., Liman, E.R., Ellis-Davies, G.C.R., McGee, A.W., Sabatini, B.L., Roberts, R.W., Arnold, D.B., 2013. Recombinant Probes for Visualizing Endogenous Synaptic Proteins in Living Neurons. Neuron 78, 971-985. doi:10.1016/j.neuron.2013.04.017 [PDF]


    Olson, C.A., Nie, J., Diep, J., Al-Shyoukh, I., Takahashi, T.T., Al-Mawsawi, L.Q., Bolin, J.M., Elwell, A.L., Swanson, S., Stewart, R., Thomson, J.A., Soh, H.T., Roberts, R.W., Sun, R., 2012. Single-Round, Multiplexed Antibody Mimetic Design through mRNA Display. Angewandte Chemie-International Edition 51, 12449-12453. doi: 10.1002/anie.201207005 [PDF]


    Olson, C.A., Adams, J.D., Takahashi, T.T., Qi, H., Howell, S.M., Wu, T.-T., Roberts, R.W., Sun, R., Soh, H.T., 2011. Rapid mRNA-Display Selection of an IL-6 Inhibitor Using Continuous-Flow Magnetic Separation. Angewandte Chemie-International Edition 50, 8295-8298. doi: 10.1002/anie.201101149 [PDF]


    Qi, X., Xia, T., Roberts, R.W., 2010. Acridine-N Peptide Conjugates Display Enhanced Affinity and Specificity for boxB RNA Targets. Biochemistry 49, 5782-5789. doi: 10.1021/bi100634h [PDF]

    Ishikawa, F.N., Curreli, M., Olson, C.A., Liao, H.-I., Sun, R., Roberts, R.W., Cote, R.J., Thompson, M.E., Zhou, C., 2010. Importance of Controlling Nanotube Density for Highly Sensitive and Reliable Biosensors Functional in Physiological Conditions. Acs Nano 4, 6914-6922. doi: 10.1021/nn101198u [PDF]


    Liao, H.-I., Olson, C.A., Hwang, S., Deng, H., Wong, E., Baric, R.S., Roberts, R.W., Sun, R., 2009. mRNA Display Design of Fibronectin-based Intrabodies That Detect and Inhibit Severe Acute Respiratory Syndrome Coronavirus Nucleocapsid Protein. Journal of Biological Chemistry 284, 17512-17520. doi: 10.1074/jbc.M901547200 [PDF]

    Ja, W.W., Carvalho, G.B., Madrigal, M., Roberts, R.W., Benzer, S., 2009. The Drosophila G protein-coupled receptor, Methuselah, exhibits a promiscuous response to peptides. Protein Science 18, 2203-2208. doi: 10.1002/pro.221 [PDF]

    Ishikawa, F.N., Chang, H.-K., Curreli, M., Liao, H.-I., Olson, C.A., Chen, P.-C., Zhang, R., Roberts, R.W., Sun, R., Cote, R.J., Thompson, M.E., Zhou, C., 2009. Label-Free, Electrical Detection of the SARS Virus N-Protein with Nanowire Biosensors Utilizing Antibody Mimics as Capture Probes. Acs Nano 3, 1219-1224. doi: 10.1021/nn900086c [PDF]


    Olson, C.A., Liao, H.-I., Sun, R., Roberts, R.W., 2008. mRNA display selection of a high-affinity, modification-specific phospho-I kappa B alpha-binding fibronectin. ACS chemical biology 3, 480-485. doi: 10.1021/cb800069c [PDF]

    Fiacco, S.V., Roberts, R.W., 2008. N-Methyl Scanning Mutagenesis Generates Protease-Resistant G Protein Ligands with Improved Affinity and Selectivity. Chembiochem : a European journal of chemical biology 9, 2200-2203. doi: 10.1002/cbic.200800208 [PDF]

    Austin, R.J., Ja, W.W., Roberts, R.W., 2008. Evolution of class-specific peptides targeting a hot spot of the G alpha s subunit. Journal of Molecular Biology 377, 1406-1418. doi: 10.1016/j.jmb.2008.01.032 [PDF]


    Olson, C.A., Roberts, R.W., 2007. Design, expression, and stability of a diverse protein library based on the human fibronectin type III domain. Protein Science 16, 476-484. doi: 10.1110/ps.062498407 [PDF]

    Millward, S.W., Fiacco, S., Austin, R.J., Roberts, R.W., 2007. Design of cyclic peptides that bind protein surfaces with antibody-like affinity. ACS chemical biology 2, 625-634. doi: 10.1021/cb7001126 [PDF]

    Ja, W.W., West, A.P., Jr., Delker, S.L., Bjorkman, P.J., Benzer, S., Roberts, R.W., 2007. Extension of Drosophila melanogaster life span with a GPCR peptide inhibitor. Nature Chemical Biology 3, 415-419. doi: 10.1038/nchembio.2007.2 [PDF]


    Ja, W.W., Wiser, O., Austin, R.J., Jan, L.Y., Roberts, R.W., 2006. Turning G proteins on and off using peptide ligands. ACS chemical biology 1, 570-574. doi: 10.1021/cb600345k [PDF]

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