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Unraveling the molecular mechanisms and regulatory networks controlling responses to thiamin (vitamin B1) or pyridoxine (vitamin B6) in Arabidopsis.

English title Unraveling the molecular mechanisms and regulatory networks controlling responses to thiamin (vitamin B1) or pyridoxine (vitamin B6) in Arabidopsis.
Applicant Fitzpatrick Teresa
Number 141117
Funding scheme Project funding
Research institution Département de Botanique & Biologie Végétale Université de Genève
Institution of higher education University of Geneva - GE
Main discipline Biochemistry
Start/End 01.11.2012 - 30.04.2016
Approved amount 502'000.00
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All Disciplines (6)

Discipline
Biochemistry
Genetics
Molecular Biology
Cellular Biology, Cytology
Botany
Agricultural and Forestry Sciences

Keywords (6)

vitamin metabolism; antioxidant; Arabidopsis thaliana; transport; crop plants; Abiotic stress

Lay Summary (French)

Lead
Les vitamines sont des micronutriments essentiels pour la survie de tous les organismes, et les êtres humains doivent obtenir ces composés par l'alimentation. Les plantes sont des sources principales de vitamines. L’importance de ces dernières pour les plantes elles-mêmes fut cependant quelque peu négligée. Dans la plupart des cas, les mécanismes physiologiques, biochimiques et moléculaires qui contribuent à leur synthèse, transport et accumulation dans les plantes restent à élucider.
Lay summary

Nous nous concentrons actuellement sur l’étude des vitamines B1 (thiamine) et B6 (pyridoxine). Ces composés revêtent une importance capitale pour la vie de tout organisme. Ceci est illustré par leur fonction de coenzyme  dans de nombreuses réactions métaboliques. La vitamine B1 est nécessaire pour l'activité catalytique des enzymes du cycle de Krebs, de la glycolyse et de la voie des pentoses phosphates, de même que la biosynthèse des acides aminés et des isoprénoïdes. Les carences en vitamine B1 représentent un problème de santé très répandu, notamment dans les pays où le riz est la composante principale du régime alimentaire. En effet, le polissage des grains supprime la plupart de la thiamine contenue dans le son. Par ailleurs, la vitamine B6 est impliquée dans plus de processus biologiques que n’importe quel autre élément nutritif. Elle est  le cofacteur d’un large éventail d'enzymes dans de nombreuses voies métaboliques, allant de la biosynthèse des acides aminés à celle des antibiotiques. Chez les plantes, celle-ci est également utilisée dans la biosynthèse de métabolites secondaires, comme les alcaloïdes par exemple. Les objectifs généraux de notre recherche sont d'établir les voies de biosynthèse de ces vitamines, de comprendre comment leur production est régulée, d’élucider leurs modes de transport, d'évaluer les effets de la sur-ou sous-accumulation et de découvrir de nouvelles fonctions ainsi que les mécanismes associés. Nous utilisons principalement Arabidopsis thaliana comme organisme modèle. Son génome est complétement séquencé et de nombreuses ressources, telles que des banques de mutants d’insertion, des données de transcriptomique ou des banques d’ADNc sont à disposition de la communauté scientifique. De tels outils facilitent grandement les études de génétique et de biologie moléculaire. Nous réalisons également ces recherches avec des plantes cultivées ainsi que des bactéries, des levures et des algues.

Direct link to Lay Summary Last update: 20.03.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Phosphorylated B6 vitamer deficiency in SALT OVERLY SENSITIVE4 mutants compromises shoot and root development
Gorelova Vera, Colinas Maite, Dell’Aglio Elisa, Flis Paulina, Salt David E, Fitzpatrick Teresa B (2021), Phosphorylated B6 vitamer deficiency in SALT OVERLY SENSITIVE4 mutants compromises shoot and root development, in Plant Physiology.
Clarification of the dispensability of PDX1.2 for Arabidopsis viability using CRISPR/Cas9
Dell’Aglio Elisa, Dalvit Ivan, Loubéry Sylvain, Fitzpatrick Teresa B. (2019), Clarification of the dispensability of PDX1.2 for Arabidopsis viability using CRISPR/Cas9, in BMC Plant Biology, 19(1), 464-464.
Crystal structure of the pseudoenzyme PDX1.2 in complex with its cognate enzyme PDX1.3: a total eclipse
Robinson Graham C., Kaufmann Markus, Roux Céline, Martinez-Font Jacobo, Hothorn Michael, Thore Stéphane, Fitzpatrick Teresa B. (2019), Crystal structure of the pseudoenzyme PDX1.2 in complex with its cognate enzyme PDX1.3: a total eclipse, in Acta Crystallographica Section D Structural Biology, 75(4), 400-415.
Balancing of B6 Vitamers Is Essential for Plant Development and Metabolism in Arabidopsis.
Colinas Maite, Eisenhut Marion, Tohge Takayuki, Pesquera Marta, Fernie Alisdair R, Weber Andreas P M, Fitzpatrick Teresa B (2016), Balancing of B6 Vitamers Is Essential for Plant Development and Metabolism in Arabidopsis., in The Plant cell, 28(2), 439-53.
Interaction between vitamin B6 metabolism, nitrogen metabolism and autoimmunity.
Colinas Maite, Fitzpatrick Teresa B (2016), Interaction between vitamin B6 metabolism, nitrogen metabolism and autoimmunity., in Plant signaling & behavior, 11(4), 1161876-1161876.
Long-Distance Transport of Thiamine (Vitamin B1) Is Concomitant with That of Polyamines.
Martinis Jacopo, Gas-Pascual Elisabet, Szydlowski Nicolas, Crèvecoeur Michèle, Gisler Alexandra, Bürkle Lukas, Fitzpatrick Teresa B (2016), Long-Distance Transport of Thiamine (Vitamin B1) Is Concomitant with That of Polyamines., in Plant physiology, 171(1), 542-53.
Consequences of a deficit in vitamin B6 biosynthesis de novo for hormone homeostasis and root development in Arabidopsis.
Boycheva Svetlana, Dominguez Ana, Rolcik Jakub, Boller Thomas, Fitzpatrick Teresa B (2015), Consequences of a deficit in vitamin B6 biosynthesis de novo for hormone homeostasis and root development in Arabidopsis., in Plant physiology, 167(1), 102-17.
Natures balancing act: examining biosynthesis de novo, recycling and processing damaged vitamin B metabolites.
Colinas Maite, Fitzpatrick Teresa B (2015), Natures balancing act: examining biosynthesis de novo, recycling and processing damaged vitamin B metabolites., in Current opinion in plant biology, 25, 98-106.
A pathway for repair of NAD(P)H in plants.
Colinas Maite, Shaw Holly V, Loubéry Sylvain, Kaufmann Markus, Moulin Michael, Fitzpatrick Teresa B (2014), A pathway for repair of NAD(P)H in plants., in The Journal of biological chemistry, 289(21), 14692-706.
High-resolution crystal structure of the eukaryotic HMP-P synthase (THIC) from Arabidopsis thaliana.
Coquille Sandrine, Roux Céline, Mehta Angad, Begley Tadhg P, Fitzpatrick Teresa B, Thore Stéphane (2013), High-resolution crystal structure of the eukaryotic HMP-P synthase (THIC) from Arabidopsis thaliana., in Journal of structural biology, 184(3), 438-44.

Collaboration

Group / person Country
Types of collaboration
Roman Ulm (University of Geneva) Switzerland (Europe)
- Research Infrastructure
Wilhelm Gruissem (ETH Zürich) Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Alisdair Fernie (MPI Golm, Germany) Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Stéphane Thore (University of Geneva) Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Exchange of personnel
Jean-Luc Wolfender (University of Geneva) Switzerland (Europe)
- Research Infrastructure
Jakub Rolcik (Olomouc, Czech Republic) Czech Republic (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
PhD program in Basic and Applied Molecular Life Sciences Talk given at a conference NAD℗H repair and vitamin B6 salvage in plants, linked together? 29.09.2014 Les Diablerets, Switzerland Colinas Martinez Maite Felicitas;
Global Plant Council "Biofortification forum" Talk given at a conference B vitamin biofortification in plants 09.07.2014 Xiamen, China Fitzpatrick Teresa;
Invited lecture Individual talk Engineering vitamin B metabolism: What benefits can we expect to reap? 09.10.2013 Oslo, Norway Fitzpatrick Teresa;
European Plant Science Organisation conference: Plants for a greening economy Poster NAD℗H repair and vitamin B6 salvage in Arabidopsis: Two distinct processes linked together? 04.09.2013 Porto Heli, Greece Colinas Martinez Maite Felicitas;
European Plant Science Organisation conference: Plants for a greening economy. Talk given at a conference Unraveling the homeostasis of two components of the vitamin B complex and their possible exploitation for beneficial purposes in plants. 04.09.2013 Porto Heli, Greece Fitzpatrick Teresa;
Gordon conference "Plant Metabolic engineering" Talk given at a conference Engineering vitamin B6 metabolism: What benefits can we expect to reap? 10.07.2013 New Hampshire, United States of America Fitzpatrick Teresa;
Invited talk at DSM Nutritional Products Ltd Individual talk 100 years since the discovery of vitamins: where are we now with vitamin B6? 16.01.2013 Kaiseraugst, Switzerland Fitzpatrick Teresa;


Communication with the public

Communication Title Media Place Year
Media relations: print media, online media A new role for vitamin B6 in plants http://biologie.unige.ch/en/2016/02/a-new-role-for-vitamin-b6-in-plants/ Western Switzerland 2016
Media relations: print media, online media Scientists report breakthrough in the quest for obese plants The conversation International 2016
Talks/events/exhibitions Fascination of Plants day Western Switzerland 2015

Awards

Title Year
EMBO short term fellowship 2014
Conference travel grant to EPSO 2014 funded by Societé academique de Genève 2013

Associated projects

Number Title Start Funding scheme
162555 Dissecting the role of vitamin B1 derivatives and the interaction between vitamin B1 homeostasis and the circadian clock. 01.07.2016 Project funding
119186 Defining vitamin B1 and B6 metabolism in plants: synthesis, regulation and transport 01.05.2008 SNSF Professorships

Abstract

The B vitamins are essential micronutrients that play well-established roles as cofactors for numerous metabolic enzymes. Plants can biosynthesize these compounds de novo from simple precursors but they must be taken in the diet of humans for which plants are a primary source. It is only recently with the advent of genomic technologies that the metabolism of these compounds is being unraveled in plants. With this knowledge it is becoming increasingly apparent that several of the B vitamins, in particular vitamin B1 (thiamin) and B6 (pyridoxine) have additional important non-cofactor functions. There is evidence that both vitamin B1 and B6 play prominent roles in the regulation of gene expression as well as the responses to both abiotic and biotic stress. However, the molecular nature of the sensing and propagation of these events remain to be unraveled. Both vitamin B1 and B6 are comprised of several compounds only one of which, in each case, is acting as the cofactor form. The role of the other members is not yet known. Therefore, an understanding of the homeostatic regulation of these compounds is necessary. As a continuation of certain aspects of the previously awarded SNSF Professorship, in this proposal we plan to focus on two very promising projects that emerged from this work. Subproject A is on the transport/trafficking of vitamin B1 in plant cells and subproject B is on the contribution of the salvage pathway of vitamin B6 biosynthesis to the general homeostasis of this set of compounds. For example, vitamin B1 in its form as thiamin diphosphate (TDP) is essential for the activity of key enzymes of glycolysis, the citric acid cycle as well as the Calvin cycle. However, TDP is synthesized in the cytosol in plants and thus, must be imported into the chloroplast and mitochondria to activate these key enzymes in the energy generating pathways of the cell. However, to date there has been no report of how trafficking of this vital metabolite occurs in a plant cell. We have begun to dissect key components of the trafficking of vitamin B1 in plants. The objectives of subproject A in this proposal are to functionally characterize these components and clarify their integration in the general metabolism of the cell using state of the art genomic, biochemical and physiological approaches. On the other hand, while de novo biosynthesis of vitamin B6 has been well characterized, there is an additional pathway (salvage pathway) that functions in the interconversion of the multiple compounds that comprise vitamin B6. We have strong evidence that components of this pathway are major players in the developmental and stress responses associated with vitamin B6. Subproject B aims to define the contribution of this pathway to the homeostasis of the vitamin B6 pool and its association with stress responses. We believe that both projects will pave the way to providing a comprehensive description of the how these metabolites are sensed and how both cofactor and non-cofactor roles are propagated.
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