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Draft:John SantaLucia, Jr.

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John SantaLucia Jr. is an American biophysical chemist known for his work on nucleic acid thermodynamics.[1]. He is an Emeritus Professor of Chemistry at Wayne State University in Detroit, Michigan[2], and the co-founder of DNA Software Inc[3].

Education and Early Career

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John SantaLucia Jr. studied chemistry as an undergraduate at Clarkson University[2]. SantaLucia earned his Ph.D. in Chemistry from the University of Rochester in 1991, under Douglas H. Turner.[4]. He conducted postdoctoral research at the University of California, Berkeley, with Ignacio Tinoco Jr., focusing on RNA structural studies using isotope-edited NMR spectroscopy[5]. There he was an NIH Post-doctoral Fellow from 1991-1994[2]. In 1994, SantaLucia joined Wayne State University as an Assistant Professor[2].

Academic Career (1994-2021)

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Thermodynamics of DNA

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Between 1996 and 1998, he published several papers describing the nearest-neighbor method for DNA thermodynamics that collectively have been cited over 10,000 times[6][7][8][9][10][11]. He developed the HYTHER web server with his student, Dr. Nicolas Peyret, to predict the thermodynamic properties of DNA and RNA sequences, including melting temperatures (Tm) [12]. These parameters enable modern PCR, microarray hybridization, DNA sequencing, and DNA nanostructure technology[13][14] [15].

Nearest-neighbor parameters developed by SantaLucia are widely used in major software packages and Tm calculators including:  UNAFold mFold[16] and DINAMelt[17], DNA Software VisualOMP[18], dnaMATE[19], Promega Tm for Oligos[20], ThermoFisher Tm calculator[21], Biosearch RealTimeDesign Software[22].

Structural Biology using NMR Spectroscopy and 3D Modeling

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SantaLucia's group used NMR spectroscopy to determine the structures of ribosomal RNA segments - the 690 loop [23][24], 790 loop[25], 970 loop[26], A-site mutants[27], and helix 69 - from the large ribosome subunit[28][29][30]. The 690 loop was the first known example of a G-U mismatch structure with a sheared geometry, leading to the discovery that the mismatch could be substituted and still retain function in vivo[24].

This work led to the development of RNA123 3D structure prediction methods [31][32][33][34]

Organic Chemistry

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SantaLucia’s work in organic synthesis includes the complete synthesis of 3-deaza-3methyl-deoxyadenosine (3mddA)[35] and 5-iodocytidine[36]. He also contributed an efficient method for synthesizing ester bonds[37]. SantaLucia also determined thermodynamic parameters for synthetic Hachimoji DNA base pairs invented by Steven A. Benner[38]. This latter collaboration was featured across news outlets, including Nature[39], Smithsonian Magazine[40], Wired[41], IFL Science[42], CNN[43], and an article by Carl Zimmer in The New York Times[44].

Commercial Career (2000 – Present)

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In 2000, SantaLucia co-founded DNA Software Inc. to develop software for predicting nucleic acid behavior[3]. He led the development of the Visual-OMP program[45], improving PCR assay optimization, including an assay for detecting the 2009 H1N1 influenza pandemic[46]. Since 2010, he has published on the Alkhumra hemorrhagic fever virus genome[47] and PCR assays for Klebsiella and the gut microbiome[48].

Service and Awards

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John SantaLucia Jr. served on the interagency “SPADA” (Stakeholder Panel on Agent Detection Assays) governmental panel, producing a 2020 report on modern molecular assay development[49].

In 2021, SantaLucia received the AOAC International Award for “Recognition of Technical and Scientific Excellence: COVID-19 Emergency Response Validation Program Advisory Group”[50]. SantaLucia's company, DNA Software, received the 2023 Technology Innovation Leadership Award for Multiplex PCR Solutions[51] from Frost & Sullivan.

References

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  1. ^ "John SantaLucia, Jr. DNA Software, Inc". PMWC Precision Medicine World Conference. 2019-02-15. Retrieved 2024-07-26.
  2. ^ a b c d "College of Liberal Arts and Sciences". Wayne State University. 2017-04-10. Retrieved 2024-07-26.
  3. ^ a b "Team". DNA Software. 2024-07-25. Retrieved 2024-07-26.
  4. ^ SantaLucia J, Turner DH (1993). "Structure of (rGGCGAGCC)2 in solution from NMR and restrained molecular dynamics". Biochemistry. 32 (47): 12612–23. doi:10.1021/bi00210a009. PMID 8251479.
  5. ^ SantaLucia J, Shen L, Cai Z, Lewis H, Ignacio T (1995). "Synthesis and NMR of RNA with selective isotopic enrichment in the bases" (PDF). Nucleic Acids Research. 23 (23): 4913–4921. doi:10.1093/nar/23.23.4913. PMC 307483. PMID 8532537.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  6. ^ Xia, Tianbing; SantaLucia, John; Burkard, Mark E.; Kierzek, Ryszard; Schroeder, Susan J.; Jiao, Xiaoqi; Cox, Christopher; Turner, Douglas H. (1998-10-01). "Thermodynamic Parameters for an Expanded Nearest-Neighbor Model for Formation of RNA Duplexes with Watson−Crick Base Pairs". Biochemistry. 37 (42): 14719–14735. doi:10.1021/bi9809425. ISSN 0006-2960.
  7. ^ SantaLucia J, Allawi HT, Seneviratne PA (1996). "Improved nearest-neighbor parameters for predicting DNA duplex stability". Biochemistry. 35 (11): 3555–62. doi:10.1021/bi951907q. PMID 8639506.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  8. ^ Allawi HT, SantaLucia J (1997). "Thermodynamics and NMR of internal G.T mismatches in DNA". Biochemistry. 36 (34): 10581–94. doi:10.1021/bi962590c. PMID 9265640.
  9. ^ SantaLucia J (1998). "A unified view of polymer, dumbbell, and oligonucleotide DNA nearest-neighbor thermodynamics". Proc Natl Acad Sci U S A. 95 (4): 1460–5. Bibcode:1998PNAS...95.1460S. doi:10.1073/pnas.95.4.1460. PMC 19045. PMID 9465037.
  10. ^ Allawi HT, SantaLucia J (1998). "Nearest neighbor thermodynamic parameters for internal G.A mismatches in DNA". Biochemistry. 37 (8): 2170–9. doi:10.1021/bi9724873. PMID 9485363.
  11. ^ Allawi HT, SantaLucia J (1998). "Nearest-neighbor thermodynamics of internal A.C mismatches in DNA: sequence dependence and pH effects". Biochemistry. 37 (26): 9435–44. doi:10.1021/bi9803729. PMID 9649326.
  12. ^ Peyret N, Seneviratne PA, Allawi HT, SantaLucia J (1999). "Nearest-neighbor thermodynamics and NMR of DNA sequences with internal A.A, C.C, G.G, and T.T mismatches". Biochemistry. 38 (12): 3468–77. doi:10.1021/bi9825091. PMID 10090733.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  13. ^ SantaLucia J, Hicks D (2004). "The thermodynamics of DNA structural motifs". Annu Rev Biophys Biomol Struct. 33: 415–40. doi:10.1146/annurev.biophys.32.110601.141800. PMID 15139820.
  14. ^ SantaLucia J, Turner DH (1997). "Measuring the thermodynamics of RNA secondary structure formation". Biopolymers. 44 (3): 309–19. doi:10.1002/(SICI)1097-0282(1997)44:3<309::AID-BIP8>3.0.CO;2-Z. PMID 9591481.
  15. ^ Watkins NE, SantaLucia J (2005). "Nearest-neighbor thermodynamics of deoxyinosine pairs in DNA duplexes". Nucleic Acids Res. 33 (19): 6258–67. doi:10.1093/nar/gki918. PMC 1277807. PMID 16264087.
  16. ^ "DNA Folding Form". www.unafold.org. Retrieved 2024-08-06.
  17. ^ "The DINAMelt Server". www.unafold.org. Retrieved 2024-08-06.
  18. ^ "Visual OMP™". DNA Software. Retrieved 2024-08-06.
  19. ^ "dnaMATE server". melolab.org. Retrieved 2024-08-06.
  20. ^ "Tm Calculator | Oligo melting temperature". www.promega.com. Retrieved 2024-08-06.
  21. ^ "Tm Calculator - US". www.thermofisher.com. Retrieved 2024-08-06.
  22. ^ "How is the Tm calculated in LGC Biosearch's Technologies' RealTimeDesign™ software?". LGC Biosearch Technologies. Retrieved 2024-08-06.
  23. ^ Morosyuk SV, Cunningham PR, SantaLucia J (2001). "Structure and function of the conserved 690 hairpin in Escherichia coli 16 S ribosomal RNA. II. NMR solution structure". J Mol Biol. 307 (1): 197–211. doi:10.1006/jmbi.2000.4431. PMID 11243814.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  24. ^ a b Morosyuk SV, SantaLucia J, Cunningham PR (2001). "Structure and function of the conserved 690 hairpin in Escherichia coli 16 S ribosomal RNA. III. Functional analysis of the 690 loop". J Mol Biol. 307 (1): 213–28. doi:10.1006/jmbi.2000.4432. PMID 11243815.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  25. ^ Lee K, Varma S, SantaLucia J, Cunningham PR (1997). "In vivo determination of RNA structure-function relationships: analysis of the 790 loop in ribosomal RNA". J Mol Biol. 269 (5): 732–43. doi:10.1006/jmbi.1997.1092. PMID 9223637.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  26. ^ Saraiya AA, Lamichhane TN, Chow CS, SantaLucia J, Cunningham PR (2008). "Identification and role of functionally important motifs in the 970 loop of Escherichia coli 16S ribosomal RNA". J Mol Biol. 376 (3): 645–57. doi:10.1016/j.jmb.2007.11.102. PMC 2262921. PMID 18177894.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  27. ^ Clos II, Lawrence J. NMR solution studies of 16S rRNA A-site functional mutants and binding of novel ligands. PhD Thesis. Wayne State University, 2007.
  28. ^ Desaulniers JP, Chang YC, Aduri R, Abeysirigunawardena SC, SantaLucia J, Chow CS (2008). "Pseudouridines in rRNA helix 69 play a role in loop stacking interactions". Org Biomol Chem. 6 (21): 3892–5. doi:10.1039/b812731j. PMID 18931791.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  29. ^ Sumita M, Jiang J, SantaLucia J, Chow CS (2012). "Comparison of solution conformations and stabilities of modified helix 69 rRNA analogs from bacteria and human". Biopolymers. 97 (2): 94–106. doi:10.1002/bip.21706. PMC 3269404. PMID 21858779.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  30. ^ Jiang J, Aduri R, Chow CS, SantaLucia J (2014). "Structure modulation of helix 69 from Escherichia coli 23S ribosomal RNA by pseudouridylations". Nucleic Acids Res. 42 (6): 3971–81. doi:10.1093/nar/gkt1329. PMC 3973299. PMID 24371282.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  31. ^ Aduri R, Psciuk BT, Saro P, Taniga H, Schlegel HB, SantaLucia J (2007). "AMBER Force Field Parameters for the Naturally Occurring Modified Nucleosides in RNA". J Chem Theory Comput. 3 (4): 1464–75. doi:10.1021/ct600329w. PMID 26633217.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  32. ^ Kazantsev AV, Rambo RP, Karimpour S, Santalucia J, Tainer JA, Pace NR (2011). "Solution structure of RNase P RNA". RNA. 17 (6): 1159–71. doi:10.1261/rna.2563511. PMC 3096047. PMID 21531920.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  33. ^ Sijenyi, F. et al. (2012). The RNA Folding Problems: Different Levels of sRNA Structure Prediction. In: Leontis, N., Westhof, E. (eds) RNA 3D Structure Analysis and Prediction. Nucleic Acids and Molecular Biology, vol 27. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-25740-7_6
  34. ^ Cruz JA, Blanchet MF, Boniecki M, Bujnicki JM, Chen SJ, Cao S; et al. (2012). "RNA-Puzzles: a CASP-like evaluation of RNA three-dimensional structure prediction". RNA. 18 (4): 610–25. doi:10.1261/rna.031054.111. PMC 3312550. PMID 22361291.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  35. ^ Irani, Rostem J.; SantaLucia, John (1999). "The synthesis of 5-iodocytidine phosphoramidite for heavy atom derivatization of RNA". Tetrahedron Letters. 40 (51). Elsevier BV: 8961–8964. doi:10.1016/s0040-4039(99)01650-0. ISSN 0040-4039.
  36. ^ Irani, R.; SantaLucia, J. (1999). "The synthesis of 5-iodocytidine phosphoramidite for heavy atom derivatization of RNA". Tetrahedron Letters. 40 (51): 8961–8964. doi:10.1016/S0040-4039(99)01650-0. S2CID 96099503.
  37. ^ Dhimitruka, Ilirian; SantaLucia, John (2006-01-01). "Investigation of the Yamaguchi Esterification Mechanism. Synthesis of a Lux-S Enzyme Inhibitor Using an Improved Esterification Method". Organic Letters. 8 (1): 47–50. doi:10.1021/ol0524048. ISSN 1523-7060. PMID 16381564.
  38. ^ Hoshika, Shuichi; Leal, Nicole A.; Kim, Myong-Jung; Kim, Myong-Sang; Karalkar, Nilesh B.; Kim, Hyo-Joong; Bates, Alison M.; Watkins, Norman E.; SantaLucia, Holly A.; Meyer, Adam J.; DasGupta, Saurja; Piccirilli, Joseph A.; Ellington, Andrew D.; SantaLucia, John; Georgiadis, Millie M.; Benner, Steven A. (2019-02-22). "Hachimoji DNA and RNA: A genetic system with eight building blocks". Science. 363 (6429): 884–887. Bibcode:2019Sci...363..884H. doi:10.1126/science.aat0971. ISSN 0036-8075. PMC 6413494. PMID 30792304.
  39. ^ Warren, Matthew (2019-02-21). "Four new DNA letters double life's alphabet". Nature. 566 (7745): 436–436. doi:10.1038/d41586-019-00650-8.
  40. ^ Magazine, Smithsonian; Thulin, Lila. "Scientists Successfully Double the DNA Alphabet". Smithsonian Magazine. Retrieved 2024-08-06.
  41. ^ Molteni, Megan. "Doubling Our DNA Building Blocks Could Lead to New Life Forms". Wired. ISSN 1059-1028. Retrieved 2024-08-06.
  42. ^ "New Artificial DNA Has Doubled The Alphabet Of Life". IFLScience. 2019-02-22. Retrieved 2024-08-06.
  43. ^ Strickland, Ashley (2019-02-21). "Synthetic DNA could help with search for alien life". CNN. Retrieved 2024-08-06.
  44. ^ Zimmer, Carl (2019-02-21). "Genetic Alphabet". The New York Times. Retrieved 2024-07-26.
  45. ^ SantaLucia J (2007). Physical principles and visual-OMP software for optimal PCR design. Methods Mol Biol. Vol. 402. pp. 3–34. doi:10.1007/978-1-59745-528-2_1. ISBN 978-1-58829-725-9. PMID 17951788.
  46. ^ Medina RA, Rojas M, Tuin A, Huff S, Ferres M, Martinez-Valdebenito C; et al. (2011). "Development and characterization of a highly specific and sensitive SYBR green reverse transcriptase PCR assay for detection of the 2009 pandemic H1N1 influenza virus on the basis of sequence signatures". J Clin Microbiol. 49 (1): 335–44. doi:10.1128/JCM.01142-10. PMC 3020443. PMID 21084522.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  47. ^ Madani TA, Azhar EI, Abuelzein el-TM, Kao M, Al-Bar HM, Farraj SA; et al. (2014). "Complete genome sequencing and genetic characterization of Alkhumra hemorrhagic fever virus isolated from Najran, Saudi Arabia". Intervirology. 57 (5): 300–10. doi:10.1159/000362334. PMID 25096447.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  48. ^ Sun Y, Patel A, SantaLucia J, Roberts E, Zhao L, Kaye K; et al. (2021). "Measurement of Klebsiella Intestinal Colonization Density To Assess Infection Risk". mSphere. 6 (3): e0050021. doi:10.1128/mSphere.00500-21. PMC 8265666. PMID 34160234.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  49. ^ SantaLucia J, Sozhamannan S, Gans JD, Koehler JW, Soong R, Lin NJ; et al. (2020). "Appendix Q: Recommendations for Developing Molecular Assays for Microbial Pathogen Detection Using Modern In Silico Approaches". J AOAC Int. 103 (4): 882–899. doi:10.1093/jaoacint/qsaa045. PMC 8370429. PMID 33241357.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  50. ^ "Analytical science leaders honored at the 2021 AOAC INTERNATIONAL Annual Meeting". AOAC INTERNATIONAL. 2021-09-24. Retrieved 2024-07-26.
  51. ^ "2023 Award Recipients". Frost & Sullivan. Retrieved 2024-08-06.
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