Rochelle Esposito

Professor Emeritus

Wolfgang Epstein

Professor Emeritus

Ursula Storb, MD

Professor Emeritus, Molecular Genetics and Cell Biology
Committee on Genetics, Genomics & Systems Biology, Committee on Cancer Biology, Committee on Immunology, Committee on Development, Regeneration & Stem Cell Biology

stor@uchicago.edu

Universitaet Freiburg, Germany, M.D.

Research Summary

Gene expression is controlled by activation and repression. Repression can be caused by methylation of cytosine in the sequence 5'CpG3'. 70% of CGs are methylated in mammals. Preventing DNA methylation is embryonic lethal because it results in uncontrolled gene activation. Very little is known about how methylation is targeted. The methylation modifier gene, Ssm1, discovered by our laboratory, is a candidate for encoding such a novel targeting function. When a transgene, HRD, comes under the influence of Ssm1, it is highly methylated at CGs and not expressed. Ssm1 acts early in embryonic development. It seems to direct methyl-transferases to its target genes. Only after DNA methylation does the target gene adopt an inactive chromatin state and cease to be transcribed. We have mapped Ssm1 to a small interval in the mouse genome and have used positional cloning to identify the Ssm1 gene. Ssm1 encodes a KRAB-ZincFinger protein. We postulate that the Zinc fingers bind DNA sequences the embryo needs to inactivate and that the KRAB domain interacts with other proteins that cause methylation of the marked DNA sequences. The characterization of Ssm1 and the determination of its endogenous targets and effects throughout development are of major importance. It will help to understand how genes are targeted for silencing in normal development and cancer.

Another project is the somatic hypermutation (SHM) of immunoglobulin genes that encode antibodies for immunity. Antibodies are produced by B lymphocytes. When these cells encounter a foreign substance, such as bacteria or viruses, they undergo a very high rate of SHM of the expressed antibody genes. SHM is initiated by a cytidine deaminase changing cytosines into uracils. In other genes, such uracils are repaired by base excision repair. However, in antibody genes during SHM, error-prone DNA polymerases introduce more errors into all four bases (A, C, G, T). In this fashion, the affinity of the antibodies vastly increases, aiding the destruction of infectious agents or cancer cells. The molecular details of the mutation mechanism, including transcription, error prone DNA repair, and the role of chromatin are a major focus of our laboratory.

Under the control of the modifier Ssm1, the HRD transgene undergoes strain-specific DNA methylation. Bisulfite analysis shows that CpG dinucleotides are almost completely methylated (red marks) in every transgene sequence in adult B6 (black mouse) but very little in D2 (beige mouse). Mice of the D2 strain express the transgene throughout life. B6 early embryos express the transgene, but starting around day 6 of embryogenesis, B6 mice cease expression when CpGs are completely methylated and inactivating chromatin changes have taken place.

Selected Publications

Kodgire, P., Mukkawar, P., North, J.A., Poirier, M. G., and Storb, U. (2012) Nucleosome stability dramatically impacts the targeting of somatic hypermutation. Mol. Cell Biol., 32:2030-2040. (PubMed)

Ratnam, S., Bozek, G., Nicolae, D., and Storb, U. (2010). The pattern of somatic hypermutation of Ig genes is altered when p53 is inactivated. Mol. Immunol., 47:2611-2618. (PubMed)

Tanaka, A., Shen, H., Ratnam, S., and Storb, U. (2010). Attracting AID to targets of somatic hypermutation. J. Exp. Med., 207:405-415. (PubMed)

Storb, U., Shen, H., and Nicolae, D. (2009). Somatic hypermutation: Processivity of the cytosine deaminase AID and error-free repair of the resulting uracils. Cell Cycle, 8:3097-3101. (PubMed)

Shen, H.M., Poirier, M.G., Allen, M., North, J., Lal, R., Widom, J., and Storb, U. (2009). The activation induced cytidine deaminase (AID) efficiently targets DNA in nucleosomes, but only during transcription. J.Exp Med., 206:1057-71. (PubMed)

Longerich, S., Orelli, B., Martin, R., Bishop, D., and Storb, U. (2008). Brca1 in Ig gene conversion and somatic hypermutation. DNA Repair, 7: 253-266. (PubMed)

Longerich, S., Meira, S., Shaw, D. Samson, L., and Storb, U. (2007). Alkyladenine glycosylase (Aag) in somatic hypermutation and class switch recombination. DNA Repair, 6:1764-1773. (PubMed)

Shen H., Tanaka, A., Bozek, G., Nicolae, D., and Storb, U. (2006). Somatic hypermutation and class switch recombination in Msh6-/-Ung-/- double-knockout mice. J. Immunol., 177:5386-5392. (PubMed)

Shen, H., Ratnam, S., and Storb, U. (2005). Targeting of the activation-induced cytosine deaminase (AID) is strongly influenced by the sequence and structure of the targeted DNA. Mol. Cell. Biol., 25:10815-10821. (PubMed)

Longerich, S., Tanaka, A., Bozek, G., Nicolae, D. and Storb, U. (2005). The very 5' end and the constant region of Ig genes are spared from somatic mutation because AID does not access these regions. J. Exp. Med., 202:1443-1454. (PubMed)

Padjen, K., Ratnam, S., and Storb, U. (2005). DNA methylation precedes chromatin modifications under the influence of the strain-specfici modifier Ssm1. Mol. Cell. Biol., 25: 4782-4791. (PubMed)

Shen, H. M. and Storb, U. (2004). Activation-induced cytidine deaminase (AID) can target both DNA strands when the DNA is supercoiled. Proc. Natl. Acad. Sci. U S A, 101: 12997-13002. (PubMed)

Michael, N., Shen, H. M., Longerich, S., Kim, N., Longacre, A. and Storb, U. (2003). The E box motif CAGGTG enhances somatic hypermutation without enhancing transcription. Immunity, 19: 235-42. (PubMed)

Sun, T., Clark, M. R. and Storb, U. (2002). A point mutation in the constant region of Ig lambda1 prevents normal B cell development due to defective BCR signaling. Immunity, 16: 245-55. (PubMed)

Michael, N., Martin, T. E., Nicolae, D., Kim, N., Padjen, K., Zhan, P., Nguyen, H., Pinkert, C. and Storb, U. (2002). Effects of sequence and structure on the hypermutability of immunoglobulin genes. Immunity, 16: 123-34. (PubMed)

Bernard Roizman, ScD

Professor Emeritus, Microbiology; Molecular Genetics and Cell Biology; Biochemistry and Molecular Biology
Committee on Genetics, Committee on Microbiology
Joseph Regenstein Chairman, Distinguished Srvc. Professor

bernard.roizman@bsd.uchicago.edu

Sc.D., Johns Hopkins, 1956

Research Summary

Herpes simplex viruses cause two kinds of infections. On initial infection at the portal of entry into the body, the virus replicates and kills the infected cell (lytic infection). In the course of its replication, the virus infects nerve endings and is transported retrograde to neuronal nuclei of peripheral ganglia where it remains latent (silent) and does not harm the neuron. In some individuals the virus periodically reactivates, and is transported anterograde to a site near the portal of entry where it can cause recurrent lesions.

The focus of the research conducted in this laboratory is on the mechanism by which herpes simplex virus with less than 100 genes takes over a human cell with more than 20,000 genes in both lytic and latent infection.

Current studies on lytic infection indicate that both the virus and the cell have evolved a large number of functions designed to thwart each other’s efforts. The cell attempts to silence viral DNA and preclude the expression of its genes. The virus has evolved a large number of functional domains in its proteins that are designed to silence the cell and prevent it from shutting down the virus. In the course of these studies we have identified both the mechanisms by which the cell attempts to shut down the virus and virus-encoded functions that instead silence the cell and block the activation cellular innate immune responses.

The exciting results of the studies on latent infection are two fold: in peripheral neurons the virus allows itself to be silenced by host repressors.  At the same time it has evolved the machinery that enables it to reactivate when the neuron harboring the latent virus is stressed by external stimuli such as fever, UV light or emotional/hormonal stress.

The laboratory has trained approximately 50 graduate students and approximately the same number of post-doctoral fellows. The majority of the trainees are in Universities engaged in research and teaching.

Selected Publications

Kalamvoki M, Du T, Roizman B. Cells infected with herpes simplex virus 1 export to uninfected cells exosomes containing STING, viral mRNAs, and microRNAs. Proc Natl Acad Sci U S A. 2014 Nov 18;111(46):E4991-6. (PubMed)

Kalamvoki M, Roizman B. HSV-1 degrades, stabilizes, requires, or is stung by STING depending on ICP0, the US3 protein kinase, and cell derivation. Proc Natl Acad Sci U S A. 2014 Feb 4;111(5):E611-7. (PubMed)

Du T, Zhou G, Roizman B. Modulation of reactivation of latent herpes simplex virus 1 in ganglionic organ cultures by p300/CBP and STAT3. Proc Natl Acad Sci U S A. 2013 Jul 9;110(28):E2621-8. (PubMed)

Zhou G, Du T, Roizman B. The role of the CoREST/REST repressor complex in herpes simplex virus 1 productive infection and in latency. Viruses. 2013 Apr 29;5(5):1208-18. Review. (PubMed)

Du T, Zhou G, Roizman B. HSV-1 gene expression from reactivated ganglia is disordered and concurrent with suppression of latency-associated transcript and miRNAs. Proc Natl Acad Sci U S A. 2011 Nov 15;108(46):18820-4. (PubMed)

Gayle K. Lamppa, PhD

Professor Emeritus, Molecular Genetics and Cell Biology
Committee on Genetics

gklamppa@uchicago.edu

B.A., Biology, Reed College, 1973
Ph.D., Plant Biology, University of Washington, 1980

Research Summary

Our major goal is to understand how the pathway of protein import into chloroplasts is regulated, and elucidate the key components involved and their functional roles. The chloroplast carries out the essential reactions of photosynthesis, and houses an amazing array of biosynthetic pathways required for plant development. The chloroplast contains its own DNA, but ~98% of its proteins are encoded by the nuclear genome and synthesized in the cytosol as precursors that must be imported. We identified a zinc-binding stromal processing peptidase (SPP) that removes targeting signals from nearly all proteins entering the chloroplast, allowing them to achieve their functional conformations. Biochemical and transgenic plant studies demonstrated that SPP has been highly conserved during evolution and is essential for plant survival. Because of its pivotal role during protein import, we are establishing how SPP recognizes its unique precursor substrates, the mechanism underlying cleavage, and how SPP activation is controlled.

To broaden our understanding of the chloroplast import pathway, we developed a novel genetic screen in the model plant Arabidopsis. An important class of mutants revealed that the regulation of protein import is integrated into a nitrogen-dependent metabolic network linked to purine catabolism. Chloroplast development and adaptation to light and abiotic stress are altered in the mutants. These findings have important implications for the timing of leaf senescence and plant productivity that depend on efficient photosynthesis and chloroplast metabolism. Our genetic screen provides a new perspective to identify the decisive factors that regulate chloroplast protein import amid a dynamic, and often challenging, cellular environment.

Selected Publications

Lamppa, G. and Zhong, R.  2013.  Chloroplast stromal processing peptidase.  IN:  Handbook of Proteolytic Enzymes.  Third edition. Eds. N. Rawlings and G. Salvese, Elsevier Ltd, London.  Invited review chapter, pp. 1442-1447.

Zhong, R. Thomspon, J., Otttesen, E., and Lamppa, G.  2010. A forward genetic screen to explore chloroplast protein import in vivo identifies Moco sulfurase, pivotal for ABA and IAA biosynthesis and purine turnover.  Plant J. 63:  44-59. (PubMed)

Ottesen, E., Zhong, R., and Lamppa, G.  2010.  Identification of a chloroplast division mutant coding for ARC6H, an ARC6 homolog that plays a nonredundant role.  Plant Science 178:  114-122.  (ScienceDirect)

Ponpuak, M., Klemba, M., Park, M., Gluzman, I., Lamppa, G. and Goldberg, D. 2007. A role for falcilysin in transit peptide degradation in the Plasmodium falciparum apicoplast. Molecular Microbiol.: 63: 314-334. (PubMed)

Richter, S., Zhong, R. and Lamppa, G. (2005) Function of the stromal processing peptidase in the chloroplast import pathway. (Review) Physiol. Plant. 123: 362-368.

Rudhe, C., Clifton, R., Chew, O., Zeman, K., Richter, R., Lamppa, G., Whelan, J., and
Glaser, E. 2004. Processing of the dual targeted precursor protein of glutathione reductase in mitochondria and chloroplasts. J. Mol. Biol. 343: 639-647. (PubMed)

Jin, R., Richter, S., Zhong, R. and Lamppa, G. K. (2003). "Expression and import of an active cellulase from a thermophilic bacterium into the chloroplast both in vitro and in vivo." Plant Mol Biol 51: 493-507. (PubMed)

Zhong, R., Wan, J., Jin, R. and Lamppa, G. (2003). "A pea antisense gene for the chloroplast stromal processing peptidase yields seedling lethals in Arabidopsis: survivors show defective GFP import in vivo." Plant J 34: 802-12. (PubMed)

Richter, S. and Lamppa, G. K. (2003). "Structural properties of the chloroplast stromal processing peptidase required for its function in transit peptide removal." J Biol Chem 278: 39497-502. (PubMed)

Richter, S. and Lamppa, G. K. (2002). "Determinants for removal and degradation of transit peptides of chloroplast precursor proteins." J Biol Chem 277: 43888-94. (PubMed)

John Reinitz

Professor: Departments of Statistics, Ecology and Evolution, Molecular Genetics & Cell Biology, and the College
Member: Institute of Genomics & Systems Biology

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?

Biosciences Graduate Program Association

Publications

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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

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

  9. 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

  10. 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

  11. 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

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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

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

  21. 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

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

  23. 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

  24. 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

  25. 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

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

  27. 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

  28. 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

  29. 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

  30. 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

  31. 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

  32. 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

  33. 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

  34. 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

  35. 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

  36. 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

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

  38. 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

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

  40. 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

  41. 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

  42. 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

  43. 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

  44. 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

  45. 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

  46. 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

  47. 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

  48. 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

  49. 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

  50. 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

  51. 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

  52. 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

  53. 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

  54. 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

  55. 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

  56. 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

  57. 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

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

  59. 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

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

  61. 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

  62. 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

  63. 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

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

  65. 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

  66. 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

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

Edwin W. Taylor, PhD

Professor Emeritus, Molecular Genetics and Cell Biology, Biochemistry and Molecular Biology
Louis Block Professor

ewt1@uchicago.edu

B.A., Physics and Chemistry University of Toronto, 1952
M.Sc., Physical Chemistry McMaster University, 1955
Ph.D., Biophysics The University of Chicago, 1957

Research Summary

We study the mechanism of molecular motors, myosin with actin and kinesin with microtubules. The objective is to show how the steps in the kinetic mechanism determine the structural changes which produce force and motion. To disect the steps in the system mutant kinesins, expressed in bacteria, are studied in which a step in the mechanism is blocked. The results are correlated with the structure of the protein and its motility properties determined by in vitro assay.

Selected Publications

Ma, Y. Z. and Taylor, E. W. (1997). "Interacting head mechanism of microtubule-kinesin ATPase." J Biol Chem 272: 724-30. (PubMed)

Ma, Y. Z. and Taylor, E. W. (1997). "Kinetic mechanism of a monomeric kinesin construct." J Biol Chem 272: 717-23. (PubMed)

Pechatnikova, E. and Taylor, E. W. (1997). "Kinetic mechanism of monomeric non-claret disjunctional protein (Ncd) ATPase." J Biol Chem 272: 30735-40. (PubMed)

Bernard S. Strauss, PhD

Professor Emeritus, Molecular Genetics and Cell Biology
Committee on Cancer Biology
Committee on Genetics, Genomics & Systems Biology

bs19@uchicago.edu

B.S., Chemistry, City College of New York, 1947
Magna cum laude Ph.D., Biochemistry and Immunology, California Institute of Technology, 1950

Research Summary

During the period from 1960 until about 2008 this laboratory was involved in studies on DNA repair and on the mechanism of mutation, particularly attempting to understand the role of polymerases and editing nucleases.

Selected Publications

Strauss B. PubMed, The New York Times, and The Chicago Tribune as Tools for Teaching Genetics. Genetics. 2005 171:1449-1454. (PubMed)

Strauss B. ROSY and JIM: The Mystery of THE DOUBLE HELIX. Perspect Biol Med. 2004 Summer;47(3):443-8. (PubMed)

Strauss BS. The "A" rule revisited: polymerases as determinants of mutational specificity. DNA Repair (Amst). 2002 Feb 28;1(2):125-35. (PubMed)

Sagher D, Karrison T, Schwartz JL, Larson R, Meier P, Strauss B. Low O6-alkylguanine DNA alkyltransferase activity in the peripheral blood lymphocytes of patients with therapy-related acute nonlymphocytic leukemia. Cancer Res. 1988 Jun 1;48(11):3084-9. (PubMed)

Sagher D, Strauss B. Insertion of nucleotides opposite apurinic/apyrimidinic sites in deoxyribonucleic acid during in vitro synthesis: uniqueness of adenine nucleotides. Biochemistry. 1983 Sep 13;22(19):4518-26. (PubMed)

Higgins NP, Kato K, Strauss B. A model for replication repair in mammalian cells. J Mol Biol. 1976 Mar 5;101(3):417-25. (PubMed)

Pauli RM, Strauss BS. Proliferation of human peripheral lymphocytes. Characteristics of cells once stimulated or re-stimulated by concanavalin A. Exp Cell Res. 1973 Dec;82(2):357-66. (PubMed)

Tsuda Y, Strauss BS. A deoxyribonuclease reaction requiring nucleoside di- or triphosphates. Biochemistry. 1964 Nov;3:1678-84. (PubMed)

Okubo S, Stodolsky M, Bott K, Strauss BS. Separation of the transforming and viral deoxyribonucleic acids of a transducing bacteriophage of Bacillus subtilis. Proc Natl Acad Sci U S A. 1963 Oct;50:679-86. (PubMed)

Strauss BS. Differential destruction of the transforming activity of damaged deoxyribonucleic acid by a bacterial enzyme. Proc Natl Acad Sci U S A. 1962 Sep 15;48:1670-5. (PubMed)

Strauss, B.S. An Outline of Chemical Genetics. 1960. W.B. Saunders. Co., Philadelphia. (books.google.com)

Theodore L. Steck, MD

Professor Emeritus, Biochemistry and Molecular Biology, Molecular Genetics and Cell Biology

tsteck@bsd.uchicago.edu

B.S., Lawrence College, 1960
M.D., Harvard Medical School, 1964

Research Summary

My long-term research interest is in membrane biochemistry. Over the years, I have studied the molecular organization of the human red cell membrane and several aspects of the cell biology of the ameba, Dictyostelium discoideum. In addition, the disposition of cell cholesterol has been a recurrent focus. We are currently investigating cellular cholesterol homeostasis: how cells sense their need for this essential plasma membrane lipid and make appropriate adjustments to keep it in balance. We suggest that cells gauge the magnitude of the bulk pool of cholesterol in the plasma membrane by sensing the high activity of the cholesterol in excess of phospholipids. This active excess sets the size of the sterol pool in the endoplasmic reticulum and mitochondria through the flow of cholesterol between the cell surface and intracellular membranes. The endoplasmic reticulum pool then sets the level of activity of several regulatory elements in its membrane that mediate sterol homeostasis while the mitochondria convert cholesterol to oxysterols that serve as messengers of cholesterol excess. The elements of this cholesterol sensing system and how it can be manipulated are under investigation.

Selected Publications

Lange, Y. and Steck, T.L. (2016). Active membrane cholesterol as a physiological effector. Chem Phys Lipids. pii: S0009-3084(16)30015-9. doi: 10.1016/j.chemphyslip.2016.02.003. (PubMed)

Czyz DM, Potluri LP, Jain-Gupta N, Riley SP, Martinez JJ, Steck TL, Crosson S, Shuman HA, Gabay JE. Host-directed antimicrobial drugs with broad-spectrum efficacy against intracellular bacterial pathogens. MBio. 2014; 5(4):e01534-14. (PubMed)

Lange Y, Ye J, Steck TL. Essentially all excess fibroblast cholesterol moves from plasma membranes to intracellular compartments. PLoS One. 2014; 9(7):e98482. (PubMed)

Tietjen GT, Gong Z, Chen CH, Vargas E, Crooks JE, Cao KD, Heffern CT, Henderson JM, Meron M, Lin B, Roux B, Schlossman ML, Steck TL, Lee KY, Adams EJ. Molecular mechanism for differential recognition of membrane phosphatidylserine by the immune regulatory receptor Tim4. Proc Natl Acad Sci U S A. 2014 Apr 15; 111(15):E1463-72. (PubMed)

Lange Y, Tabei SM, Ye J, Steck TL. Stability and stoichiometry of bilayer phospholipid-cholesterol complexes: relationship to cellular sterol distribution and homeostasis. Biochemistry. 2013 Oct 8; 52(40):6950-9. (PubMed)

Lange, Y., Ye, J., and Steck, T.L. (2012) Activation mobilizes the cholesterol in the late endosomes-lysosomes of Niemann Pick Type C cells. PLoS One 7, e30051. (PubMed)

Steck, T.L., and Lange, Y. (2010) Cell cholesterol homeostasis: Mediation by active cholesterol. Trends in Cell Biology 20, 680-687. (PubMed)

Lange, Y., Ye, J., Duban, M.-E., and Steck, T. L. (2009) Activation of Membrane Cholesterol by 63 Amphipaths. Biochemistry 48, 8505-8515. (PubMed)

Lange, Y., Steck, T. L., Ye, J., Lanier, M. H., Molugu, V., and Ory, D. (2009) Regulation of fibroblast mitochondrial 27-hydroxycholesterol production by active plasma membrane cholesterol. Journal of Lipid Research 50, 1881-1888. (PubMed)

Lange, Y., and Steck, T.L. (2008). Cholesterol homeostasis and the escape tendency (activity) of plasma membrane cholesterol. Prog Lipid Res 47, 319-332. (PubMed)

Lange, Y., Ory, D.S., Ye, J., Lanier, M.H., Hsu, F.-F., and Steck, T.L. (2008). Effectors of Rapid Homeostatic Responses of Endoplasmic Reticulum Cholesterol and 3-Hydroxy-3-methylglutaryl-CoA Reductase. J Biol Chem 283, 1445-1455. (PubMed)

Ratajczak, M.K., Ko, Y.T.C., Lange, Y., Steck, T.L., and Lee, K.Y.C. (2007). Cholesterol Displacement from Membrane Phospholipids by Hexadecanol. Biophys J 93, 2038-2047. (PubMed)

Lange Y, Ye J, Steck TL. (2007). Scrambling of phospholipids activates red cell membrane cholesterol. Biochemistry. 46(8):2233-8. (PubMed)

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