Biology and Biological EngineeringHOME
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.
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.
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.
- Conditional Dicer substrate formation via shape and sequence transduction with small conditional RNAsJ 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 economyProc Natl Acad Sci USA, 110(40):16163-16168, 2013.
- Selective nucleic acid capture with shielded covalent probesJ Am Chem Soc, 135(26):9691-9699, 2013. (pdf) (supp info)
- Nucleic acid sequence design via efficient ensemble defect optimizationJ Comput Chem, 32:439-452, 2011. (pdf) (supp info) (supp structures)
- NUPACK: Analysis and design of nucleic acid systemsJ Comput Chem, 32:170-173, 2011. (pdf)
- Programmable in situ amplification for multiplexed imaging of mRNA expressionNature Biotechnol, 28:1208-1212, 2010. (pdf) (supp movie 1) (supp movie 2)(supp info)
- Selective cell death mediated by small conditional RNAsProc 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 RNAsProc Natl Acad Sci USA, 110(1):384, 2013. (pdf)
- Programming biomolecular self-assembly pathwaysNature, 451:318-322, 2008. (pdf) (supp info)
- An autonomous polymerization motor powered by DNA hybridizationNature Nanotech, 2(8):490-494, 2007. (pdf) (supp info)
- Thermodynamic analysis of interacting nucleic acid strandsSIAM Rev, 49(1):65-88, 2007. (pdf)
- Topological constraints in nucleic acid hybridization kineticsNucleic Acids Res, 33(13):4090-4095, 2005. (pdf)
- Triggered amplification by hybridization chain reactionProc Natl Acad Sci USA, 101(43):15275-15278, 2004. (pdf)
- A synthetic DNA walker for molecular transportJ Am Chem Soc, 126:10834-10835, 2004. (pdf) (supp info)
- Rewritable memory by controllable nanopatterning of DNANano Lett, 4(5):905-909, 2004. (pdf) (supp info)
- An algorithm for computing nucleic acid base-pairing probabilities including pseudoknotsJ Comput Chem, 25:1295-1304, 2004. (pdf)
- Adjoint and defect error bounding and correction for functional estimatesJ Comput Phys, 200:769-794, 2004. (pdf)
- Paradigms for computational nucleic acid designNucleic Acids Res, 32(4):1392-1403, 2004. (pdf) (supp info text) (supp info sequences)
- A partition function algorithm for nucleic acid secondary structure including pseudoknotsJ Comput Chem, 24(13):1664-1677, 2003. (pdf) (supp info)
- Exact rotamer optimization for protein designJ Comput Chem, 24(2):232-243, 2003. (pdf)
- Algorithm developments for discrete adjoint methodsAIAA J, 41(2):198-205, 2003. (pdf)
- Protein design is NP-hardProtein Engineering, 15(10):779-782, 2002. (pdf)
- Analytic adjoint solutions for the quasi-one-dimensional Euler equationsJ Fluid Mech, 426:327-345, 2001. (pdf)
- Conformational splitting: a more powerful criterion for dead-end eliminationJ Comput Chem, 21(11):999-1009, 2000. (pdf)
- Adjoint recovery of superconvergent functionals from PDE approximationsSIAM Rev, 42(2):247-264, 2000. (pdf)
- An introduction to the adjoint approach to designFlow Turb Comb, 65:393-415, 2000. (pdf)
- Optimum aerodynamic design using the Navier-Stokes equationsTheor Comput Fluid Dyn, 10:213-237, 1998. (pdf)
- Efficient computation of unsteady viscous flows by an implicit preconditioned multigrid methodAIAA J, 36(3):401-408, 1998. (pdf)
- Preconditioned multigrid methods for compressible flow calculations on stretched meshesJ Comput Phys, 136:425-445, 1997. (pdf)