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Associate

Nicole Leal

Education

  • BS in Microbiology and Cell Science. University of Florida (1999)
  • PhD in Microbiology and Cell Science. University of Florida (2004)
  • Postdoctoral Research Associate. Microbiology and Cell Science, University of Florida (2004)
  • Postdoctoral Research Associate. Department of Chemistry, University of Florida (2005)
  • Associate Scientist at the Foundation for Applied Molecular Evolution, Alachua, FL (2006-current)

Research summary

My research in the Benner group has focused on the development of a SNAP2, novel technique for the detection of specific DNA and/or RNA molecules in a biological mixture. This technique uses short oligonucleotide primers (6-8mers) that are complementary to a target sequence under conditions of dynamic equilibrium. The primers are modified such that an imine bond is formed when they are in close proximity, allowing for the discriminatory power of short oligonucleotide duplexes and an overall specificity of priming characteristic of longer oligonucleotides (14-16mers). In theory, these primers will only snap together, prime and extend in the presence of the target sequence. This technology can be applied towards the development of various DNA assays including the detection of single nucleotide changes within a target sequence.

I have also been working on the molecular aspects of reversibly terminated DNA sequencing. I have been involved in the development and optimization of Sequencing during Synthesis reactions (SdS) using reversible terminators. This technology can be applied to the development of a faster and less expensive method for genomic sequencing.

In the field of synthetic biology, I have been involved in developing the manipulative and analytical technology needed to support the conversion of six-letter information encoded in DNA to give the corresponding information in encoding RNA molecules in vitro. I have shown that T7 RNA polymerase and reverse transcriptase catalyze the transcription and reverse transcription of xNA (DNA or RNA) having two complementary AEGIS nucleobases, specifically Z and P. This work sets the stage for the next step in the development of an AEGIS synthetic biology, including the use of DNA containing extra codons based on the AEGIS expanded alphabet to encode mRNA and tRNA that might increase the number of amino acids within the protein lexicon.

Recent Publications

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Synthesis and Enzymology of 2'-Deoxy-7-deazaisoguanosine Triphosphate and Its Complement: A Second Generation Pair in an Artificially Expanded Genetic Information System
Karalkar NB, Leal NA, Kim MS, Bradley KM, Benner SA
ACS Synthetic Biology , American Chemical Society (2016) doi: 10.1021/acssynbio.5b00276
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Transcription, Reverse Transcription, and Analysis of RNA Containing Artificial Genetic Components
Nicole A. Leal, Hyo-Joong Kim, Shuichi Hoshika, Myong-Jung Kim, Matthew A. Carrigan, and Steven A. Benner
ACS Synthetic Biology , American Chemical Society (2015) Apr 17;4(4):407-13. doi: 10.1021/sb500268n
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Ribonucleosides for an Artificially Expanded Genetic Information System
Hyo-Joong Kim, Nicole A. Leal, Shuichi Hoshika, Steven A. Benner
J. Org. Chem. (2014) 79 (7), pp 3194-3199
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Directed Evolution of Polymerases To Accept Nucleotides with Nonstandard Hydrogen Bond Patterns
Laos R, Shaw R, Leal NA, Gaucher E, Benner S.
Biochemistry (2013) 52, 5288-5294
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Conversion strategy using an expanded genetic alphabet to assay nucleic acids
Yang, Z., Durante, M., Glushakova, L., Sharma, N., Leal, N., Bradley, K., Chen, F., Benner, S. A.
Anal. Chem. (2013) 85(9):4705-12
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Labeled nucleoside triphosphates with reversibly terminating aminoalkoxyl groups
Hutter, D; Kim, MJ; Karalkar, N; Leal, NA; Chen, F; Guggenheim, E; Visalakshi, V; Olejnik, J; Gordon, S; Benner, SA
Nuc. Nuc. Nuc. acids 29 (11) 879-895 (2010)
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Artificial Genetic Systems: Self-Avoiding DNA in PCR and Multiplexed PCR
Hoshika, S; Chen, F; Leal, NA; Benner, SA
Angew. Chem. Int. Ed. 49 (32) 5554-5557 (2010)

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Reconstructed evolutionary adaptive paths give polymerases accepting reversible terminators for sequencing and SNP detection
Chen, F; Gaucher, EA; Leal, NA; Hutter, D; Havemann, SA; Govindarajan, S; Ortlund, EA; Benner, SA
Proc. Natl. Acad. Sci. USA 107 (5) 1948-1953 (2010)

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2'-Deoxy-1-methylpseudocytidine, a stable analog of 2'-deoxy-5-methylisocytidine
Kim, HJ; Leal, NA; Benner, SA
Bioorg. Med. Chem. 17 (10) 3728-3732 (2009)
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Self-Avoiding Molecular Recognition Systems (SAMRS)
Hoshika, S; Chen, F; Leal, NA; Benner, SA
Nucleic Acids Symp. Ser. 52 (1) 129-130 (2008)

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