Novartis Finance Corporation

Ciba-geigy Corporation

Metabolon, Inc.

Novartis Ag

Novartis Corporation

Ciba-geigy Ag

John A. Ryals

Shericca C. Williams

Robert M. Goodman

Danny C. Alexander

Jeffrey R. Stinson

Mary B. Moyer

George B. Payne

Eric R. Ward

Jean-marc Neuhaus

John A Ryals

Scott Joseph Uknes

Eric R Ward

Leslie B Friedrich

James Joseph Beck

Dwight Steven Hill

Philip E Hammer

Stephen T Lam

Robert M Goodman

James M Ligon

Danny C Alexander

Thomas Schupp

Jeffrey R Stinson

Christian T Harms

George B Payne

Mary B Moyer

Terrence Patrick Delaney

Christoph Sperisen

Kay A Lawton

Thomas D Gaffney

Eric Russell Ward

Frederich Meins, Jr

Henry-York Steiner

Jean-Marc Neuhaus

Michael V Milburn

Matthew W Mitchell

Helmut Kessmann

Hideaki Shinshi

John H Duesing

Alice Montoya, Deceased

Klaus Maleck

Shericca C Williams

Patricia A Ahl-Goy

Philippe B Gay

Kristianna Baldwin Weymann

Jan Hofsteenge

Herman C Wenzler

Frederick Meins, Jr

Gertrude Knauf-Beiter

James Madison Ligon

Wilhelm Ruess

Lining Guo

Ruth Beatrice Kung

Adam D Kennedy

Jacob Wulff

Snezana Neff

Daniel Murray Ellis

Michael Oostendorp

Thomas Boller

Andrea Eckhart

Michelle Denise Hunt

Bernardus T Vernooij

Thomas J Jönsson

Ryan Douglas Michalek

Bryan Wittmann

Daniel P Stevens

Mike Milburn

Pieter Vos

Alfred Scheidegger

Atsuko Nagai-Hayashi

Taco Peter Jesse

Antonio Molina-Fernandez

Jr Meins Frederick

Methods are described herein for small molecule biochemical profiling of an individual subject for diagnosis of a disease or disorder, facilitating diagnosis of a disease or disorder, and/or identifying an increased risk of developing a disease or disorder in the individual subject. Aberrant levels of small molecules present in a sample from an individual subject are identified and diagnostic information relevant to the individual subject is obtained based on the identified aberrant levels. The obtained diagnostic information includes one or more of an identification of at least one biochemical pathway associated with the identified subset of the small molecules having aberrant levels, an identification at least one disease or disorder associated with the identified subset of the small molecules having aberrant levels, and an identification of at least one recommended follow up test associated with the identified subset of the small molecules having aberrant levels.

Small molecule biochemical profiling of individual subjects for disease diagnosis and health assessment

Methods for metabolomically determining the biological affects of compounds are described.

Methods of identifying biochemical pathways

Biomarkers relating to metabolic age are provided, as well as methods for using such biomarkers as biomarkers for determining metabolic age. In addition, methods for modulating the metabolic age of a subject are also provided. Also provided are suites of small molecule entities as biomarkers for metabolic age.

Biomarkers related to metabolic age and methods using the same

The present invention provides chemically regulatable DNA sequences capable of regulating transcription of an associated DNA sequence in plants or plant tissues, chimeric constructions containing such sequences, vectors containing such sequences and chimeric constructions, and transgenic plants and plant tissues containing these chimeric constructions. In one aspect, the chemically regulatable DNA sequences of the invention are derived from the 5&prime; region of genes encoding pathogenisis-related (PR) proteins. The present invention also provides anti-pathogenic sequences derived from novel cDNAs coding for PR proteins which can be genetically engineered and transformed into plants to confer enhanced resistance to disease. Also provided is a method for the exogenous regulation of gene expression in plants, which comprises obtaining a plant incapable of regulating at least one gene or gene family, or at least one heterologous gene, due to the deactivation of at least one endogenous signal transduction cascade which regulates the gene in the plant, and applying a chemical regulator to the plant at a time when expression of the gene is desired. A novel signal peptide sequence and corresponding DNA coding sequence is also provided. Further provided are assays for the identification and isolation of additional chemically regulatable DNA sequences and cDNAs encoding PR proteins and assays for identifying chemicals capable of exogenously regulating the chemically regulatable DNA sequences of the invention.

DNA sequences encoding polypeptides having beta-1,3-glucanase activity

DNA sequences encoding polypeptides having &bgr;-1,3-glucanase activity

Methods are provided for selecting parental plants exhibiting disease resistance and for using these plants in breeding programs. In one method of the invention, constitutive immunity (cim) mutants are screened for either resistance to a pathogen of interest or for the expression of systemic acquired resistance (SAR) genes. Such mutants having the desired traits or expressing the desired genes are then used in breeding programs. Parent plants can also be selected based on the constitutive expression of SAR genes. These mutants are phenotypically normal yet exhibit a significant level of disease resistance. Also disclosed are lesion-simulating-disease (lsd) mutants having a lesion mimic phenotype that also express SAR genes and exhibit disease resistance. Further disclosed are non-inducible immunity (nim) mutants that do not express SAR genes, even when induced by a pathogen. Methods of use for these mutants are also disclosed.

Mutant plants and uses therefor

Method for breeding disease resistance into plants

The invention concerns the location and characterization of a gene (designated NIM1) that is a key component of the SAR pathway and that in connection with chemical and biological inducers enables induction of SAR gene expression and broad spectrum disease resistance in plants. The invention further concerns transformation vectors and processes for overexpressing the NIM1 gene in plants. The transgenic plants thus created have broad spectrum disease resistance.

Gene encoding a protein involved in the signal transduction cascade

Method for selecting disease resistant mutant plants

The present invention relates to novel peptide fragments [targeting signal] that are obtainable from the C-terminal region [C-terminal extension] of plant vacuole proteins and that, in operable linkage with any desired protein molecule, ensure that the proteins associated with those peptide fragments are directed specifically into the plant vacuole, and to DNA molecules coding for the said peptide fragments. The present invention relates also to recombinant DNA molecules that comprise the DNA sequence according to the invention in operable linkage with an expressible DNA, and to the vectors derived therefrom. Also included are host cells and/or host organisms, including transgenic plants, that comprise the said recombinant DNA or the vectors derived therefrom. The present invention also relates to recombinant DNA molecules and vectors derived therefrom that comprise DNA sequences naturally coding for vacuolar proteins, but which are devoid of vacuole signal sequences and targeted for extracellular secretion.

Signal sequences for vacuolar sorting

The present invention concerns a method of protecting plants from pathogen attack through synergistic disease resistance attained by applying a conventional microbicide to immunomodulated plants. Immunomodulated plants are those in which SAR is activated and are therefore referred to as 'SAR-on' plants. Immunomodulated plants may be provided in at least three different ways: by applying to plants a chemical inducer of SAR such as BTH, INA, or SA; through a selective breeding program based on constitutive expression of SAR genes and/or a disease-resistant phenotype; or by transforming plants with one or more SAR genes such as a functional form of the NIM1 gene. By concurrently applying a microbicide to an immunomodulated plant, disease resistance is unexpectedly synergistically enhanced; i.e., the level of disease resistance is greater than the expected additive levels of disease resistance.

Method for protecting plants

The NIM1 gene product is a structural homologue of the mammalian signal transduction factor I.kappa.B subclass .alpha.. The present invention exploits this discovery to provide altered forms of NIM1 that act as dominant-negative regulators of the systemic acquired resistance (SAR) signal transduction pathway. These altered forms of NIM1 confer the opposite phenotype as the nim1 mutant in plants transformed with the altered forms of NIM1; i.e., the transgenic plants exhibit constitutive SAR gene expression and a constitutive immunity (CIM) phenotype. The present invention further concerns DNA molecules encoding altered forms of the NIM1 gene, expression vectors containing such DNA molecules, and plants and plant cells transformed therewith. The invention also concerns methods of activating SAR in plants and conferring to plants a CIM phenotype and broad spectrum disease resistance by transforming the plants with DNA molecules encoding altered forms of the NIM1 gene product.

Altered forms of the NIM1 gene conferring disease resistance in plants

The present invention provides chemically regulatable DNA sequences capable of regulating transcription of an associated DNA sequence in plants or plant tissues, chimeric constructions containing such sequences, vectors containing such sequences and chimeric constructions, and transgenic plants and plant tissues containing these chimeric constructions. In one aspect, the chemically regulatable DNA sequences of the invention are derived from the 5' region of genes encoding pathogenisis-related (PR) proteins. The present invention also provides anti-pathogenic sequences derived from novel cDNAs coding for PR proteins which can be genetically engineered and transformed into plants to confer enhanced resistance to disease. Also provided is a method for the exogenous regulation of gene expression in plants, which comprises obtaining a plant incapable of regulating at least one gene or gene family, or at least one heterologous gene, due to the deactivation of at least one endogenous signal transduction cascade which regulates the gene in the plant, and applying a chemical regulator to the plant at a time when expression of the gene is desired A novel signal peptide sequence and corresponding DNA coding sequence is also provided. Further provided are assays for the identification and isolation of additional chemically regulatable DNA sequences and cDNAs encoding PR proteins and assays for identifying chemicals capable of exogenously regulating the chemically regulatable DNA sequences of the invention.

Inducible herbicide resistance

The present invention provides chemically regulatable DNA sequences capable of regulating transcription of an associated DNA sequence in plants or plant tissues, chimeric constructions containing such sequences, vectors containing such sequences and chimeric constructions, and transgenic plants and plant tissues containing these chimeric constructions. In one aspect, the chemically regulatable DNA sequences of the invention are derived from the 5' region of genes encoding pathogenisis-related (PR) proteins. The present invention also provides anti-pathogenic sequences derived from novel cDNAs coding for PR proteins which can be genetically engineered and transformed into plants to confer enhanced resistance to disease. Also provided is a method for the exogenous regulation of gene expression in plants, which comprises obtaining a plant incapable of regulating at least one gene or gene family, or at least one heterologous gene, due to the deactivation of at least one endogenous signal transduction cascade which regulates the gene in the plant, and applying a chemical regulator to the plant at a time when expression of the gene is desired. A novel signal peptide sequence and corresponding DNA coding sequence is also provided. Further provided are assays for the identification and isolation of additional chemically regulatable DNA sequences and cDNAs encoding PR proteins and assays for identifying chemicals capable of exogenously regulating the chemically regulatable DNA sequences of the invention.

DNA encoding plant chitinases

The present invention provides chemically regulatable DNA sequences capable of regulating transcription of an associated DNA sequence in plants or plant tissues, chimeric constructions containing such sequences, vectors containing such sequences and chimeric constructions, and transgenic plants and plant tissues containing these chimeric constructions. In one aspect, the chemically regulatable DNA sequences of the invention are derived from the 5' region of genes encoding pathogenisis-related (PR) proteins. The present invention also provides anti-pathogenic sequences derived from novel cDNAs coding for PR proteins which can be genetically engineered and transformed into plants to confer enhanced resistance to disease. Also provided is a method for the exogenous regulation of gene expression in plants, which comprises obtaining a plant incapable of regulating at least one gene or gene family, or at least one heterologous gene, due to the deactivation of at least one endogenous signal transduction cascade which regulates the gene in the plant, and applying a chemical regulator to the plant at a time when expression of the gene is desired. A novel signal peptide sequence and corresponding DNA coding sequence is also provided Further provided are assays for the identification and isolation of additional chemically regulatable DNA sequences and cDNAs encoding PR proteins and assays for identifying chemicals capable of exogenously regulating the chemically regulatable DNA sequences of the invention.

Method of protecting plants from oomycete pathogens

Growing community of inventors

Durham, NC, United States of America

John A Ryals