Water availability is a major limitation for crop productivity. Over 34 % of crop and livestock production loss is traced to drought, costing the sector $37 billion overall. Our group applies chemical biology to understand drought tolerance and to develop biotechnological tools to fight climate change. In an attempt to make discoveries with an impact in agriculture, we study different plant species including maize, rice and tomato but also model plants like Arabidopsis and the C4-monocot model Setaria viridis. During the last years we have followed a drug discovery approach to design, screen, synthesize and evaluate small molecules able to activate drought resistance in crops. Structure-guided ligand design is a powerful approach, no frequently used in plant biology, which has allowed us to develop potent ABA-receptor agonists. We are collaborating with the private sector to further improve these compounds. In the next years, we will extend our research to different targets in order to develop novel chemical probes with biotechnological interest.
¤ Corresponding author
¤ Corresponding author.
** Equal contribution.
32. Structure-Based Modulation of the Ligand Sensitivity of a Tomato Dimeric Abscisic Acid Receptor Through a Glu to Asp Mutation in the Latch Loop. Front Plant Sci. 2022 Jun 6;13:884029. doi: 10.3389/fpls.2022.884029.
31. Franco-Aragón D, García-Maquilón I, Manicardi A, Rodriguez PL, Lozano-Juste J¤. Evaluation of the anti-transpirant activity of ABA-receptor agonists in monocot and eudicot plants. Environmental Responses in Plants Methods and Protocols (Ed. Paula Duque, Dóra Szakonyi). Methods in Molecular Biology. 2022; 1064-3745, vol 2494, ISBN 978-1-0716-2296-4.
30. Lourdes Infantes**, Maria Rivera-Moreno**, MiguelDaniel-Mozo, Juan Luis Benavente, Javier Ocaña, Alberto Coego, Jorge Lozano-Juste, Pedro L. Rodriguez and Armando Albert. Structure-based modulation of the ligand sensitivity of a tomato dimeric abscisic acid receptor through a Glu to Asp mutation in the latch loop. Front. Plant Sci. 2022; 13:884029. doi: 10.3389/fpls.2022.884029
29. PYL1- and PYL8-like ABA Receptors of Nicotiana benthamiana Play a Key Role in ABA Response in Seed and Vegetative Tissue. Cells. 2022 Feb 24;11(5):795. doi: 10.3390/cells11050795.
28. Coego A, Julian J, Lozano-Juste J, Pizzio GA, Alrefaei AF, Rodriguez PL. Ubiquitylation of ABA Receptors and Protein Phosphatase 2C Coreceptors to Modulate ABA Signaling and Stress Response. Int J Mol Sci. 2021 Jul 1;22(13):7103.doi: 10.3390/ijms22137103.
27. Ruiz-Partida R, Rosario SM, Lozano-Juste J¤. An Update on Crop ABA Receptors. Plants (Basel). 2021 May 28;10(6):1087. doi: 10.3390/plants10061087.
26. García-Maquilón I, Coego A, Lozano-Juste J, Messerer M, de Ollas C, Julian J, Ruiz-Partida R, Pizzio G, Belda-Palazón B, Gomez-Cadenas A, Mayer KFX, Geiger D, Alquraishi SA, Alrefaei AF, Ache P, Hedrich R, Rodriguez PL. PYL8 ABA receptors of Phoenix dactylifera play a crucial role in response to abiotic stress and are stabilized by ABA. J Exp Bot. 2021 Feb 2;72(2):757-774. doi: 10.1093/jxb/eraa476.
25. García-Maquilón I, Rodriguez PL, Vaidya AS, Lozano-Juste J¤. A luciferase reporter assay to identify chemical activators of ABA signaling. Plant Chemical Genomics Methods and Protocols (Ed. Glenn Hicks and Chunhua Zhang). Methods in Molecular Biology. 2021;2213:113-121. doi: 10.1007/978-1-0716-0954-5_10.
24. Lozano-Juste J¤, García-Maquilón I**, Brea J**, Piña R, Albert A, Rodriguez PL, Loza MI. Identification of ABA receptor agonists using a multiplexed high-throughput chemical screening. Plant Chemical Genomics Methods and Protocols (Ed. Glenn Hicks and Chunhua Zhang). Methods in Molecular Biology. 2021;2213:99-111. doi: 10.1007/978-1-0716-0954-5_9.
23. Lozano-Juste J, Alrefaei AF, Rodriguez PL. Plant Osmotic Stress Signaling: MAPKKKs Meet SnRK2s. Trends Plant Sci. 2020 Dec;25(12):1179-1182. doi: 10.1016/j.tplants.2020.09.003.
22. Lozano-Juste J¤, García-Maquilón I, Ruiz-Partida R, Rodriguez PL. Drug Discovery for Thirsty Crops. Trends Plant Sci. 2020 Sep;25(9):844-846. doi: 10.1016/j.tplants.2020.07.001.
21. Fernandez MA**, Belda-Palazon B**, Julian J, Coego A, Lozano-Juste J, Inigo S, Rodriguez L, Bueso E, Goossens A, Rodriguez PL. RBR-type E3 ligases and the Ub-conjugating enzyme UBC26 regulate ABA receptor levels and signaling. Plant Physiol. 2019 Nov 7. doi: 10.1104/pp.19.00898.
20. Lozano-Juste J¤, Masi M, Cimmino A, Clement S, Fernández MA, Antoni R, Meyer S, Rodriguez PL, Evidente A¤. The fungal sesquiterpenoid pyrenophoric acid B uses the plant ABA biosynthetic pathway to inhibit seed germination. J Exp Bot. 2019 Oct 15;70(19):5487-5494. doi: 10.1093/jxb/erz306.
19. Julian J**, Coego A**, Lozano-Juste J, Lechner E, Wu Q, Zhang X, Merilo E, Belda-Palazon B, Park SY, Cutler SR, An C, Genschik P, Rodriguez PL. The MATH-BTB BPM3 and BPM5 subunits of Cullin3-RING E3 ubiquitin ligases target PP2CA and other clade A PP2Cs for degradation. Proc Natl Acad Sci U S A. 2019 Jul 30;116(31):15725-15734. doi: 10.1073/pnas.1908677116.
18. Belda-Palazon B, Gonzalez-Garcia MP, Lozano-Juste J, Coego A, Antoni R, Julian J, Peirats-Llobet M, Rodriguez L, Berbel A, Dietrich D, Fernandez MA, Madueño F, Bennett MJ, Rodriguez PL. PYL8 mediates ABA perception in the root through non-cell-autonomous and ligand-stabilization-based mechanisms. Proc Natl Acad Sci U S A. 2018 Dec 11;115(50):E11857-E11863. doi: 10.1073/pnas.1815410115.
17. Vaidya AS, Peterson FC, Yarmolinsky D, Merilo E, Verstraeten I, Park SY, Elzinga D, Kaundal A, Helander J, Lozano-Juste J, Otani M, Wu K, Jensen DR, Kollist H, Volkman BF, Cutler SR. A Rationally Designed Agonist Defines Subfamily IIIA Abscisic Acid Receptors As Critical Targets for Manipulating Transpiration. ACS Chem Biol. 2017 Nov 17;12(11):2842-2848. doi: 10.1021/acschembio.7b00650.
16. Moreno-Alvero M, Yunta C, Gonzalez-Guzman M, Lozano-Juste J, Benavente JL, Arbona V, Menéndez M, Martinez-Ripoll M, Infantes L, Gomez-Cadenas A, Rodriguez PL, Albert A. Structure of Ligand-Bound Intermediates of Crop ABA Receptors Highlights PP2C as Necessary ABA Co-receptor. Mol Plant. 2017 Sep 12;10(9):1250-1253. doi: 10.1016/j.molp.2017.07.004.
15. Ling Y, Alshareef S, Butt H, Lozano-Juste J, Li L, Galal AA, Moustafa A, Momin AA, Tashkandi M, Richardson DN, Fujii H, Arold S, Rodriguez PL, Duque P, Mahfouz MM. Pre-mRNA splicing repression triggers abiotic stress signaling in plants. Plant J. 2017 Jan;89(2):291-309. doi:10.1111/tpj.1338
14. Lozano-Juste J, Cutler SR. Hormone signalling: ABA has a breakdown. Nat Plants. 2016 Sep 6;2(9):16137. doi: 10.1038/nplants.2016.137.
13. Castillo MC**, Lozano-Juste J**, González-Guzmán M, Rodriguez L, Rodriguez PL, León J. Inactivation of PYR/PYL/RCAR ABA receptors by tyrosine nitration may enable rapid inhibition of ABA signaling by nitric oxide in plants. Sci Signal. 2015 Sep 1;8(392):ra89. doi: 10.1126/scisignal.aaa7981.
12. Rodriguez PL, Lozano-Juste J. Unnatural agrochemical ligands for engineered abscisic acid receptors. Trends Plant Sci. 2015 Jun;20(6):330-2. doi: 10.1016/j.tplants.2015.04.001.
11. Lozano-Juste J, Cutler SR. Plant genome engineering in full bloom. Trends Plant Sci. 2014 May;19(5):284-7. doi: 10.1016/j.tplants.2014.02.014.
10. León J, Castillo MC, Coego A, Lozano-Juste J, Mir R. Diverse functional interactions between nitric oxide and abscisic acid in plant development and responses to stress. J Exp Bot. 2014 Mar;65(4):907-21. doi: 10.1093/jxb/ert454.
9. Gibbs DJ, Md Isa N, Movahedi M, Lozano-Juste J, Mendiondo GM, Berckhan S, Marín-de la Rosa N, Vicente Conde J, Sousa Correia C, Pearce SP, Bassel GW, Hamali B, Talloji P, Tomé DF, Coego A, Beynon J, Alabadí D, Bachmair A, León J, Gray JE, Theodoulou FL, Holdsworth MJ. Nitric oxide sensing in plants is mediated by proteolytic control of group VII ERF transcription factors. Mol Cell. 2014 Feb 6;53(3):369-79. doi: 10.1016/j.molcel.2013.12.020.
8. Mosquna A, Peterson FC, Park SY, Lozano-Juste J, Volkman BF, Cutler SR. Potent and selective activation of abscisic acid receptors in vivo by mutational stabilization of their agonist-bound conformation. Proc Natl Acad Sci U S A. 2011 Dec 20;108(51):20838-43. doi: 10.1073/pnas.1112838108.
7. Peto A, Lehotai N, Lozano-Juste J, León J, Tari I, Erdei L, Kolbert Z. Involvement of nitric oxide and auxin in signal transduction of copper-induced morphological responses in Arabidopsis seedlings. Ann Bot. 2011 Sep;108(3):449-57. doi: 10.1093/aob/mcr176.
6. Lozano-Juste J, León J. Nitric oxide regulates DELLA content and PIF expression to promote photomorphogenesis in Arabidopsis. Plant Physiol. 2011 Jul;156(3):1410-23. doi: 10.1104/pp.111.177741.
5. Lozano-Juste J, Colom-Moreno R, León J. In vivo protein tyrosine nitration in Arabidopsis thaliana. J Exp Bot. 2011 Jun;62(10):3501-17. doi: 10.1093/jxb/err042.
4. Alvarez C**, Lozano-Juste J**, Romero LC, García I, Gotor C, León J. Inhibition of Arabidopsis O-acetylserine(thiol)lyase A1 by tyrosine nitration. J Biol Chem. 2011 Jan 7;286(1):578-86. doi: 10.1074/jbc.M110.147678.
3. Lozano-Juste J, León J. Nitric oxide modulates sensitivity to ABA. Plant Signal Behav. 2010 Mar;5(3):314-6.
2. Lozano-Juste J, León J. Enhanced abscisic acid-mediated responses in nia1nia2noa1-2 triple mutant impaired in NIA/NR- and AtNOA1-dependent nitric oxide biosynthesis in Arabidopsis. Plant Physiol. 2010 Feb;152(2):891-903. doi: 10.1104/pp.109.148023.
1. March-Díaz R, García-Domínguez M, Lozano-Juste J, León J, Florencio FJ, Reyes JC. Histone H2A.Z and homologues of components of the SWR1 complex are required to control immunity in Arabidopsis. Plant J. 2008 Feb;53(3):475-87.
Research lines (current):
7. Structure-guided drug design and identification of new drug targets to improve drought tolerance in crops. PID2021-128826OA-I00. 01/09/2022 – 31/08/2025. IP: Jorge Lozano-Juste. Entidades participantes: IBMCP-UPV-CSIC (España). Fuente de financiación: Ministerio de Ciencia e Innovación (MCIN, Spain), Agencia Estatal de Investigación (AEI, Spain) and Fondo Europeo de Desarrollo Regional (FEDER, European Union).
6. Chemical biology to improve drought tolerance in crops. RYC2020-029097-I. 01/01/2022 – 31/12/26. IP: Jorge Lozano-Juste. Entidades participantes: IBMCP-UPV-CSIC (España). Fuente de financiación: Ayudas Ramon y Cajal. Ministerio de Ciencia, Innovación y Universidades.
5. Improvement of rice varieties, using CRISPR/Cas9, to obtain drought and salt tolerant plants. FONDOCYT2018 2C1-182 01/01/2020-31/12/2022. IP: Sttefany Rosario Co-IP: Jorge Lozano-Juste, Concha Domingo y Luis Matos. Entidades participantes: Universidad Autónoma de Santo Domingo (República Dominicana), IBMCP-CSIC-UPV (España), IVIA (España). Fuente de financiación: FONDOCYT 2019.
Research lines (completed):
4. Mejora de la tolerancia a la sequía de plantas de cosecha usando nuevas moléculas químicas. GV/2020/159. 01/01/2020-31/12/2021. IP: Jorge Lozano-Juste. Entidades participantes: IBMCP-CSIC-UPV (España). Fuente de financiación: Proyectos de I+D+i desarrollados por Grupos de Investigación Emergentes. Generalitat Valenciana.
3. Desarrollo de agroquímicos para mejorar la resistencia a la sequía de plantas de cosecha. SP20180340 (PAID-06-18). 01/01/2019 – 31-12-2020. IP: Jorge Lozano-Juste. Entidades participantes: IBMCP-CSIC-UPV. Fuente de financiación: Universidad Politécnica de Valencia.
2. DroughtDrugs: a drug discovery approach to improve drought resistance in crop plants. RTC-2017-6019-2. 05/12/2018 – 31/12/2021. IP: GalChimia S.A. Co-IP: Mabel Loza (USC), Armando Albert (CSIC), Pedro L. Rodriguez (CSIC), Juan Carlos Estevez (USC). Entidades participantes: GalChimia S.A., CiQUS-USC, CiMUS-USC, IQFR-CSIC, IBMCP-CSIC-UPV. Fuente de financiación: Ministerio de Ciencia e Innovación. Fondos FEDER. Coordinador técnico: Jorge Lozano-Juste
1. DrugCrops: Drug discovery to improve drought tolerance in crops. H2020-MSCA-707477. 01/05/2017-30/05/2019. IP: Jorge Lozano-Juste. Entidades participantes: CiQUS-USC, IQFR-CSIC, IBMCP-CSIC-UPV. Fuente de financiación: European Union H2020-Marie Curie.
