Niles A. Pierce

Professor of Applied and Computational Mathematics and Bioengineering
B.S.E., Princeton University, 1993; D.Phil., University of Oxford, 1997. Assistant Professor of Applied Mathematics, Caltech, 2000; Assistant Professor of Applied and Computational Mathematics, 2000-04; Assistant Professor of Applied and Computational Mathematics and Bioengineering, 2004-06; Associate Professor, 2006-10; Professor, 2010-; Acting Executive Officer for Bioengineering, 2007; Executive Officer for Bioengineering, 2007-13; Executive Officer for Biological Engineering, 2013.

Small Conditional RNAs

Our work is focused on engineering small conditional RNAs (scRNAs) that interact and change conformation to execute molecular logic in vitro, in situ, and in vivo. This research program exploits the programmable chemistry of nucleic acid base-pairing.

Molecular Instruments

To read out and regulate the state of biological systems, we seek to engineer small conditional RNAs that function as programmable molecular instruments within intact biological specimens. Technical support for multiplexed bioimaging using HCR in situ amplification is available at molecularinstruments.org.

Molecular Programming

To enable the systematic design of small conditional RNAs that execute diverse dynamic functions, we are working to develop mathematically rigorous, physically sound, computationally efficient algorithms for programming molecular function. Current algorithms are available at nupack.org. Our long-term goal is to develop a compiler for molecular programming that takes as input a modular conceptual device design and provides as output the sequences of scRNAs that interact to implement the desired function.

Mapping Free Energy Landscapes

To better elucidate and control the function of small conditional RNAs, we are working to model and experimentally validate the thermodynamic and kinetic properties of the free energy landscapes encoded within scRNA sequences.

Selected Publications 
  • Conditional Dicer substrate formation via shape and sequence transduction with small conditional RNAsL.M. Hochrein, M. Schwarzkopf, M. Shahgholi, P. Yin, and N.A. PierceJ Am Chem Soc, 135(46):17322-17330, 2013.
  • Localizing transcripts to single cells suggests an important role of uncultured deltaproteobacteria in the termite gut hydrogen economyA.Z. Rosenthal, X. Zhang, K.S. Lucey, E.A. Ottesen, V. Trivedi, H.M.T. Choi, N.A. Pierce, and J.R. LeadbetterProc Natl Acad Sci USA, 110(40):16163-16168, 2013.
  • Selective nucleic acid capture with shielded covalent probesJ.R. Vieregg, H.M. Nelson, B.M. Stoltz, and N.A. PierceJ Am Chem Soc, 135(26):9691-9699, 2013. (pdf) (supp info)
  • Nucleic acid sequence design via efficient ensemble defect optimizationJ.N. Zadeh, B.R. Wolfe, and N.A. PierceJ Comput Chem, 32:439-452, 2011. (pdf) (supp info) (supp structures)
  • NUPACK: Analysis and design of nucleic acid systemsJ.N. Zadeh, C.D. Steenberg, J.S. Bois, B.R. Wolfe, M.B. Pierce, A.R. Khan, R.M. Dirks, and N.A. PierceJ Comput Chem, 32:170-173, 2011. (pdf)
  • Programmable in situ amplification for multiplexed imaging of mRNA expressionH.M.T. Choi, J.Y. Chang, L.A. Trinh, J.E. Padilla, S.E. Fraser, and N.A. PierceNature Biotechnol, 28:1208-1212, 2010. (pdf) (supp movie 1) (supp movie 2)(supp info)
  • Selective cell death mediated by small conditional RNAsS. Venkataraman, R.M. Dirks, C.T. Ueda, and N.A. PierceProc Natl Acad Sci USA, 107(39):16777-16782, 2010. (pdf) (supp info) 
    Note: this paper has been retracted. Retraction for Venkataraman et al., Selective cell death mediated by small conditional RNAsR.M. Dirks, C.T. Ueda, and N.A. PierceProc Natl Acad Sci USA, 110(1):384, 2013. (pdf)
  • Programming biomolecular self-assembly pathwaysP. Yin, H.M.T. Choi, C.R. Calvert, and N.A. PierceNature, 451:318-322, 2008. (pdf) (supp info)
  • An autonomous polymerization motor powered by DNA hybridizationS. Venkataraman, R.M. Dirks, P.W.K. Rothemund, E. Winfree, and N.A. PierceNature Nanotech, 2(8):490-494, 2007. (pdf) (supp info)
  • Thermodynamic analysis of interacting nucleic acid strandsR.M. Dirks, J.S. Bois, J.M. Schaeffer, E. Winfree, and N.A. PierceSIAM Rev, 49(1):65-88, 2007. (pdf)
  • Topological constraints in nucleic acid hybridization kineticsJ.S. Bois, S.Venkataraman, H.M.T. Choi, A.J. Spakowitz, Z.-G. Wang, and N.A. PierceNucleic Acids Res, 33(13):4090-4095, 2005. (pdf)
  • Triggered amplification by hybridization chain reactionR.M. Dirks and N.A. PierceProc Natl Acad Sci USA, 101(43):15275-15278, 2004. (pdf)
  • A synthetic DNA walker for molecular transportJ.-S. Shin and N.A. PierceJ Am Chem Soc, 126:10834-10835, 2004. (pdf) (supp info)
  • Rewritable memory by controllable nanopatterning of DNAJ.-S. Shin and N.A. PierceNano Lett, 4(5):905-909, 2004. (pdf) (supp info)
  • An algorithm for computing nucleic acid base-pairing probabilities including pseudoknotsR.M. Dirks and N.A. PierceJ Comput Chem, 25:1295-1304, 2004. (pdf)
  • Adjoint and defect error bounding and correction for functional estimatesN.A. Pierce and M.B. GilesJ Comput Phys, 200:769-794, 2004. (pdf)
  • Paradigms for computational nucleic acid designR.M. Dirks, M. Lin, E. Winfree, and N.A. PierceNucleic Acids Res, 32(4):1392-1403, 2004. (pdf) (supp info text) (supp info sequences)
  • A partition function algorithm for nucleic acid secondary structure including pseudoknotsR.M. Dirks and N.A. PierceJ Comput Chem, 24(13):1664-1677, 2003. (pdf) (supp info)
  • Exact rotamer optimization for protein designD.B. Gordon, G.K. Hom, S.L. Mayo, and N.A. PierceJ Comput Chem, 24(2):232-243, 2003. (pdf)
  • Algorithm developments for discrete adjoint methodsM.B. Giles, M.C. Duta, J.-D. Mueller, and N.A. PierceAIAA J, 41(2):198-205, 2003. (pdf)
  • Protein design is NP-hardN.A. Pierce and E. WinfreeProtein Engineering, 15(10):779-782, 2002. (pdf)
  • Analytic adjoint solutions for the quasi-one-dimensional Euler equationsM.B. Giles and N.A. PierceJ Fluid Mech, 426:327-345, 2001. (pdf)
  • Conformational splitting: a more powerful criterion for dead-end eliminationN.A. Pierce, J.A. Spriet, J. Desmet, and S.L. MayoJ Comput Chem, 21(11):999-1009, 2000. (pdf)
  • Adjoint recovery of superconvergent functionals from PDE approximationsN.A. Pierce and M.B. GilesSIAM Rev, 42(2):247-264, 2000. (pdf)
  • An introduction to the adjoint approach to designM.B. Giles and N.A. PierceFlow Turb Comb, 65:393-415, 2000. (pdf)
  • Optimum aerodynamic design using the Navier-Stokes equationsA. Jameson, L. Martinelli, and N.A. PierceTheor Comput Fluid Dyn, 10:213-237, 1998. (pdf)
  • Efficient computation of unsteady viscous flows by an implicit preconditioned multigrid methodN.A. Pierce and J.J. AlonsoAIAA J, 36(3):401-408, 1998. (pdf)
  • Preconditioned multigrid methods for compressible flow calculations on stretched meshesN.A. Pierce and M.B. GilesJ Comput Phys, 136:425-445, 1997. (pdf)
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