John Reinitz

Research Summary
My laboratory is engaged in a long term project to understand how DNA sequence specifies biological form. We are interested not only in the specification of typical form by a typical genome, but also in the effects of variability. Such variability might take the form of genetic variation in a population or intrinsic fluctuations in an individual. These problems touch on issues central to developmental and evolutionary biology, and efforts to solve them have previously led to the development of new branches of mathematics. We consider these issues in the specific context of segment determination in the fruit fly Drosophila melanogaster, but actively seek collaborations with investigators working on other organisms or with pure theoreticians. The starting point for our own investigations are quantitative data on gene expression, extracted from images of confocally scanned fixed or living embryos. We use this numerical information to find parameter sets for specific models of fundamental processes of gene regulation and pattern formation by means of large scale optimization procedures performed on parallel computers. These models may be specified in terms of DNA sequence or be more coarse-grained. They might take the form of a dynamical system, deterministic or stochastic, or simply be a complex but explicit mathematical function. Our goal is to use every tool in the toolbox—wet experiments, statistics, computational science, and mathematics—to solve a well focused scientific problem: how does a fly go from DNA sequence to a fate map of presumptive segments at single cell resolution?
  1. Barr K, Reinitz J, Radulescu O. An in silico analysis of robust but fragile gene regulation links enhancer length to robustness. PLoS Comput Biol. 2019 11; 15(11):e1007497. View in: PubMed

  2. Reinitz J, Vakulenko S, Grigoriev D, Weber A. Adaptation, fitness landscape learning and fast evolution. F1000Res. 2019; 8:358. View in: PubMed

  3. Ramos AF, Reinitz J. Physical implications of so(2, 1) symmetry in exact solutions for a self-repressing gene. J Chem Phys. 2019 Jul 28; 151(4):041101. View in: PubMed

  4. Barr KA, Reinitz J. Correction: A sequence level model of an intact locus predicts the location and function of nonadditive enhancers. PLoS One. 2018; 13(5):e0197211. View in: PubMed

  5. Barr KA, Martinez C, Moran JR, Kim AR, Ramos AF, Reinitz J. Synthetic enhancer design by in silico compensatory evolution reveals flexibility and constraint in cis-regulation. BMC Syst Biol. 2017 Nov 29; 11(1):116. View in: PubMed

  6. Barr KA, Reinitz J. A sequence level model of an intact locus predicts the location and function of nonadditive enhancers. PLoS One. 2017; 12(7):e0180861. View in: PubMed

  7. Hope CM, Rebay I, Reinitz J. DNA Occupancy of Polymerizing Transcription Factors: A Chemical Model of the ETS Family Factor Yan. Biophys J. 2017 Jan 10; 112(1):180-192. View in: PubMed

  8. Bertolino E, Reinitz J. The analysis of novel distal Cebpa enhancers and silencers using a transcriptional model reveals the complex regulatory logic of hematopoietic lineage specification. Dev Biol. 2016 May 01; 413(1):128-44. View in: PubMed

  9. Lou Z, Reinitz J. Parallel Simulated Annealing Using an Adaptive Resampling Interval. Parallel Comput. 2016 Apr 01; 53:23-31. View in: PubMed

  10. Lee U, Skinner JJ, Reinitz J, Rosner MR, Kim EJ. Noise-Driven Phenotypic Heterogeneity with Finite Correlation Time in Clonal Populations. PLoS One. 2015; 10(7):e0132397. View in: PubMed

  11. Jiang P, Ludwig MZ, Kreitman M, Reinitz J. Natural variation of the expression pattern of the segmentation gene even-skipped in melanogaster. Dev Biol. 2015 Sep 01; 405(1):173-81. View in: PubMed

  12. Ramos AF, Hornos JE, Reinitz J. Gene regulation and noise reduction by coupling of stochastic processes. Phys Rev E Stat Nonlin Soft Matter Phys. 2015 Feb; 91(2):020701. View in: PubMed

  13. Grigoriev D, Reinitz J, Vakulenko S, Weber A. Punctuated evolution and robustness in morphogenesis. Biosystems. 2014 Sep; 123:106-13. View in: PubMed

  14. Martinez C, Rest JS, Kim AR, Ludwig M, Kreitman M, White K, Reinitz J. Ancestral resurrection of the Drosophila S2E enhancer reveals accessible evolutionary paths through compensatory change. Mol Biol Evol. 2014 Apr; 31(4):903-16. View in: PubMed

  15. Lee U, Frankenberger C, Yun J, Bevilacqua E, Caldas C, Chin SF, Rueda OM, Reinitz J, Rosner MR. A prognostic gene signature for metastasis-free survival of triple negative breast cancer patients. PLoS One. 2013; 8(12):e82125. View in: PubMed

  16. Surkova S, Myasnikova E, Kozlov KN, Pisarev A, Reinitz J, Samsonova M. Quantitative imaging of gene expression in Drosophila embryos. Cold Spring Harb Protoc. 2013 Jun 01; 2013(6):488-97. View in: PubMed

  17. Surkova S, Myasnikova E, Kozlov KN, Pisarev A, Reinitz J, Samsonova M. Preparation of Drosophila embryos for quantitative imaging of gene expression. Cold Spring Harb Protoc. 2013 Jun 01; 2013(6):533-6. View in: PubMed

  18. Martinez CA, Barr KA, Kim AR, Reinitz J. A synthetic biology approach to the development of transcriptional regulatory models and custom enhancer design. Methods. 2013 Jul 15; 62(1):91-8. View in: PubMed

  19. Kim AR, Martinez C, Ionides J, Ramos AF, Ludwig MZ, Ogawa N, Sharp DH, Reinitz J. Rearrangements of 2.5 kilobases of noncoding DNA from the Drosophila even-skipped locus define predictive rules of genomic cis-regulatory logic. PLoS Genet. 2013; 9(2):e1003243. View in: PubMed

  20. Surkova S, Golubkova E. Quantitative dynamics and increased variability of segmentation gene expression in the Drosophila Krüppel and knirps mutants. Dev Biol. 2013 Apr 01; 376(1):99-112. View in: PubMed

  21. Jaeger J. Drosophila blastoderm patterning. Curr Opin Genet Dev. 2012 Dec; 22(6):533-41. View in: PubMed

  22. Kozlov K, Surkova S, Myasnikova E, Reinitz J, Samsonova M. Modeling of gap gene expression in Drosophila Kruppel mutants. PLoS Comput Biol. 2012; 8(8):e1002635. View in: PubMed

  23. Reinitz J. Turing centenary: Pattern formation. Nature. 2012 Feb 22; 482(7386):464. View in: PubMed

  24. Gursky VV, Panok L, Myasnikova EM. Mechanisms of gap gene expression canalization in the Drosophila blastoderm. BMC Syst Biol. 2011; 5:118. View in: PubMed

  25. Surkova SIu, Gurskii VV, Reinitz J, Samsonova MG. [Studies of stability mechanisms of early embryonal development of fruit fly Drosophila]. Ontogenez. 2011 Jan-Feb; 42(1):3-19. View in: PubMed

  26. Vakulenko S. Size regulation in the segmentation of Drosophila: interacting interfaces between localized domains of gene expression ensure robust spatial patterning. Phys Rev Lett. 2009 Oct 16; 103(16):168102. View in: PubMed

  27. Canalization of gene expression in the Drosophila blastoderm by gap gene cross regulation. PLoS Biol. 2009 Mar; 7(3):e1000049. View in: PubMed

  28. Kozlov KN, Myasnikova E, Samsonova AA, Surkova S, Reinitz J, Samsonova M. GCPReg package for registration of the segmentation gene expression data in Drosophila. Fly (Austin). 2009 Apr-Jun; 3(2):151-6. View in: PubMed

  29. Surkova SY, Myasnikova EM, Kozlov KN, Samsonova AA, Reinitz J, Samsonova MG. Methods for Acquisition of Quantitative Data from Confocal Images of Gene Expression in situ. Cell tissue biol. 2008 Apr; 2(2):200-215. View in: PubMed

  30. Canalization of gene expression and domain shifts in the Drosophila blastoderm by dynamical attractors. PLoS Comput Biol. 2009 Mar; 5(3):e1000303. View in: PubMed

  31. Myasnikova E, Surkova S, Panok L, Samsonova M, Reinitz J. Estimation of errors introduced by confocal imaging into the data on segmentation gene expression in Drosophila. Bioinformatics. 2009 Feb 01; 25(3):346-52. View in: PubMed

  32. Pisarev A, Poustelnikova E, Samsonova M, Reinitz J. FlyEx, the quantitative atlas on segmentation gene expression at cellular resolution. Nucleic Acids Res. 2009 Jan; 37(Database issue):D560-6. View in: PubMed

  33. Surkova S, Myasnikova E, Janssens H, Kozlov KN, Samsonova AA, Reinitz J, Samsonova M. Pipeline for acquisition of quantitative data on segmentation gene expression from confocal images. Fly (Austin). 2008 Mar-Apr; 2(2):58-66. View in: PubMed

  34. Surkova SIu, Miasnikova EM, Kozlov KN, Samsonova AA, Reinitz J, Samsonova MG. [Methods for acquisition of quantitative from confocal images of gene expression in situ]. Tsitologiia. 2008; 50(4):352-69. View in: PubMed

  35. Gurskii VV, Kozlov KN, Samsonov AM, Reinitz J. [A model with asymptotically stable dynamics for the network of Drosophila gap genes]. Biofizika. 2008 Mar-Apr; 53(2):235-49. View in: PubMed

  36. Surkova S, Kosman D, Kozlov K. Characterization of the Drosophila segment determination morphome. Dev Biol. 2008 Jan 15; 313(2):844-62. View in: PubMed

  37. Wu YF, Myasnikova E, Reinitz J. Master equation simulation analysis of immunostained Bicoid morphogen gradient. BMC Syst Biol. 2007 Nov 16; 1:52. View in: PubMed

  38. Reinitz J. Developmental biology: a ten per cent solution. Nature. 2007 Jul 26; 448(7152):420-1. View in: PubMed

  39. Jaeger J, Sharp DH, Reinitz J. Known maternal gradients are not sufficient for the establishment of gap domains in Drosophila melanogaster. Mech Dev. 2007 Feb; 124(2):108-28. View in: PubMed

  40. Jaeger J, Reinitz J. On the dynamic nature of positional information. Bioessays. 2006 Nov; 28(11):1102-11. View in: PubMed

  41. Janssens H, Hou S, Jaeger J, Kim AR, Myasnikova E, Sharp D, Reinitz J. Quantitative and predictive model of transcriptional control of the Drosophila melanogaster even skipped gene. Nat Genet. 2006 Oct; 38(10):1159-65. View in: PubMed

  42. Perkins TJ, Jaeger J, Reinitz J, Glass L. Reverse engineering the gap gene network of Drosophila melanogaster. PLoS Comput Biol. 2006 May; 2(5):e51. View in: PubMed

  43. Lebrecht D, Foehr M, Smith E, Lopes FJ, Vanario-Alonso CE, Reinitz J, Burz DS, Hanes SD. Bicoid cooperative DNA binding is critical for embryonic patterning in Drosophila. Proc Natl Acad Sci U S A. 2005 Sep 13; 102(37):13176-81. View in: PubMed

  44. Janssens H, Kosman D, Vanario-Alonso CE, Jaeger J, Samsonova M, Reinitz J. A high-throughput method for quantifying gene expression data from early Drosophila embryos. Dev Genes Evol. 2005 Jul; 215(7):374-81. View in: PubMed

  45. Myasnikova E, Samsonova M, Kosman D, Reinitz J. Removal of background signal from in situ data on the expression of segmentation genes in Drosophila. Dev Genes Evol. 2005 Jun; 215(6):320-6. View in: PubMed

  46. Jaeger J, Blagov M, Kosman D, Kozlov KN. Dynamical analysis of regulatory interactions in the gap gene system of Drosophila melanogaster. Genetics. 2004 Aug; 167(4):1721-37. View in: PubMed

  47. Jaeger J, Surkova S, Blagov M, Janssens H, Kosman D, Kozlov KN. Dynamic control of positional information in the early Drosophila embryo. Nature. 2004 Jul 15; 430(6997):368-71. View in: PubMed

  48. Poustelnikova E, Pisarev A, Blagov M, Samsonova M, Reinitz J. A database for management of gene expression data in situ. Bioinformatics. 2004 Sep 22; 20(14):2212-21. View in: PubMed

  49. Gursky VV, Reinitz J, Samsonov AM. How gap genes make their domains: An analytical study based on data driven approximations. Chaos. 2001 Mar; 11(1):132-141. View in: PubMed

  50. Myasnikova E, Samsonova A, Samsonova M, Reinitz J. Support vector regression applied to the determination of the developmental age of a Drosophila embryo from its segmentation gene expression patterns. Bioinformatics. 2002; 18 Suppl 1:S87-95. View in: PubMed

  51. Holloway DM, Reinitz J, Spirov A, Vanario-Alonso CE. Sharp borders from fuzzy gradients. Trends Genet. 2002 Aug; 18(8):385-7. View in: PubMed

  52. Kozlov K, Myasnikova E, Pisarev A, Samsonova M, Reinitz J. A method for two-dimensional registration and construction of the two-dimensional atlas of gene expression patterns in situ. In Silico Biol. 2002; 2(2):125-41. View in: PubMed

  53. Aizenberg I, Myasnikova E, Samsonova M, Reinitz J. Temporal classification of Drosophila segmentation gene expression patterns by the multi-valued neural recognition method. Math Biosci. 2002 Mar; 176(1):145-59. View in: PubMed

  54. Wu X, Vasisht V, Kosman D, Reinitz J, Small S. Thoracic patterning by the Drosophila gap gene hunchback. Dev Biol. 2001 Sep 01; 237(1):79-92. View in: PubMed

  55. Myasnikova E, Samsonova A, Kozlov K, Samsonova M, Reinitz J. Registration of the expression patterns of Drosophila segmentation genes by two independent methods. Bioinformatics. 2001 Jan; 17(1):3-12. View in: PubMed

  56. Myasnikova EM, Kosman D, Reinitz J, Samsonova MG. Spatio-temporal registration of the expression patterns of Drosophila segmentation genes. Proc Int Conf Intell Syst Mol Biol. 1999; 195-201. View in: PubMed

  57. Spirov AV, Bowler T, Reinitz J. HOX Pro: a specialized database for clusters and networks of homeobox genes. Nucleic Acids Res. 2000 Jan 01; 28(1):337-40. View in: PubMed

  58. Hewitt GF, Strunk BS, Margulies C, Priputin T, Wang XD, Amey R, Pabst BA, Kosman D, Reinitz J, Arnosti DN. Transcriptional repression by the Drosophila giant protein: cis element positioning provides an alternative means of interpreting an effector gradient. Development. 1999 Mar; 126(6):1201-10. View in: PubMed

  59. Sharp DH, Reinitz J. Prediction of mutant expression patterns using gene circuits. Biosystems. 1998 Jun-Jul; 47(1-2):79-90. View in: PubMed

  60. Reinitz J, Kosman D, Vanario-Alonso CE, Sharp DH. Stripe forming architecture of the gap gene system. Dev Genet. 1998; 23(1):11-27. View in: PubMed

  61. Kosman D, Reinitz J, Sharp DH. Automated assay of gene expression at cellular resolution. Pac Symp Biocomput. 1998; 6-17. View in: PubMed

  62. Kosman D, Small S, Reinitz J. Rapid preparation of a panel of polyclonal antibodies to Drosophila segmentation proteins. Dev Genes Evol. 1998 Jul; 208(5):290-4. View in: PubMed

  63. Reinitz J, Mjolsness E, Sharp DH. Model for cooperative control of positional information in Drosophila by bicoid and maternal hunchback. J Exp Zool. 1995 Jan 01; 271(1):47-56. View in: PubMed

  64. Wright LW, Lichter JB, Reinitz J, Shifman MA, Kidd KK, Miller PL. Computer-assisted restriction mapping: an integrated approach to handling experimental uncertainty. Comput Appl Biosci. 1994 Jul; 10(4):435-42. View in: PubMed

  65. Reinitz J, Sharp DH. Mechanism of eve stripe formation. Mech Dev. 1995 Jan; 49(1-2):133-58. View in: PubMed

  66. Reinitz J, Vaisnys JR. Theoretical and experimental analysis of the phage lambda genetic switch implies missing levels of co-operativity. J Theor Biol. 1990 Aug 09; 145(3):295-318. View in: PubMed

  67. Reinitz J, Levine M. Control of the initiation of homeotic gene expression by the gap genes giant and tailless in Drosophila. Dev Biol. 1990 Jul; 140(1):57-72. View in: PubMed

  68. Mjolsness E, Sharp DH, Reinitz J. A connectionist model of development. J Theor Biol. 1991 Oct 21; 152(4):429-53. View in: PubMed