Investigating the role of plasma membrane H+-ATPases as upstream regulators of TORC1 in plants
- Supervisor: Bruno André
- Research center: Physiologie moléculaire de la cellule
- Research start date: 15.10.2019
TORC1 (Target of Rapamycin Complex 1) is a highly conserved kinase complex playing a central role in controlling cell growth in probably all eukaryotes. It is regulated by multiple cues including amino acid availability. Although the mechanisms of TORC1 control by amino acids have been well investigated in human cells, they remain poorly known in other species. A recent study showed that in yeast, TORC1 activation upon amino acid uptake via amino-acid/H+ co-transporters is in fact triggered by the influx of H+. This H+ uptake is sensed by the plasma membrane H+-ATPase that would activate a signaling pathway targeting TORC1. Furthermore, recent observations indicate that this mechanism could be conserved in plants, which would mean that fungi and plants share a major TORC1 control mechanism. This project aims to use tobacco plant and the derived BY-2 cell line as model systems to investigate the role of H+-ATPases in TORC1 regulation. The perspective is to unravel a major mechanism controlling cell growth in plants, which might provide important novel opportunities of biotechnological applications.
I am a Ph.D. in Biotechnology. I presented my thesis in June 2015, focused on the regulation of ion homeostasis (and specifically the role of Hal4 and Hal5 kinases in plasma membrane transporter trafficking) as well as the reciprocal connection between potassium and TOR signaling pathway in the model organism Saccharomyces cerevisiae. My Ph.D. studies, together with my studies in Biotechnology have provided me with a solid background in protein biochemistry, yeast genetics and molecular biology. In the pasts years, I have taken part in two different independent research projects on ion homeostasis through the study of mechanisms of plasma membrane ion transporter post-translational regulation. I have experience in cellular signaling. I have also experience in enzymology and Bioprocess Technology optimizing industrially relevant protein surface expression in Escherichia coli from my final year project research. I did my first postdoctoral studies at the Children’s Nutrition Research Center doing research on the basic mechanisms of plant nutrient transport and creating rationale strategies for the nutritional enhancement of crops. Specifically, I worked with the H+-Pyrophosphatase from Arabidopsis thaliana (AVP1) characterizing a novel function of this protein to work in reverse and synthesize pyrophosphate (PPi) by heterologous expression of AVP1 in Saccharomyces cerevisiae, as well as, in the in vitro characterization of the catalytic domains important for AVP1 PPi synthase activity by approaches based on site-directed mutagenesis using yeast, and in the in vivo characterization of AVP1 as PPi synthase using whole plant systems. I have recently been funded to start my second postdoc at the Laboratory of Molecular Physiology of the Cell in the Université Libre de Bruxelles where I aim to dissect the role of plant H+-ATPases in TORC1 regulation.
15/10/2019- present. PostDoc fellow at the laboratory of Molecular Physiology of the Cell in the Université Libre de Bruxelles. Fellow at the IF@ULB (Marie Skłodowska-Curie Actions-COFUND) Postdoctoral Training Program. * Postdoctoral research as a fellow in the IF@ULB postdoctoral training program in Dr. Andre´s laboratory at Université Libre de Bruxelles.
04/07/17 – 02/08/2019. PostDoc Associate at the Children's Nutrition Research Center (CNRC). Fellow at the CNRC Postdoctoral Training Program. Children’s Nutrition Research Center, Department of Pediatrics Nutrition, Baylor College of Medicine, Houston (USA). * Postdoctoral research as a fellow in the CNRC postdoctoral training program in the plant nutrition field in Dr. Hirschi´s laboratory at Baylor College of Medicine.
05/07/16 - 03/07/17. Research Associate at the Children's Nutrition Research Center (CNRC). Children's Nutrition Research Center, Department of Pediatrics Nutrition, Baylor College of Medicine, Houston (USA). * Postdoctoral research in the plant nutrition field in Dr. Hirschi´s laboratory at Baylor College of Medicine.
01/09/2010 - 19/06/2015. Ph.D. in Biotechnology at the Universidad Politécnica de Valencia, Valencia (Spain). Mecanismos de regulación post-traduccional de transportadores de la membrana plasmática: Papel de las quinasas Hal4 y Hal5 en el tráfico de transportadores de nutrientes e iones en el organismo modelo Saccharomyces cerevisiae (Mechanisms of post-translational regulation on plasma membrane transporters: Role of Hal4 and Hal5 kinases on nutrient and ion transporter trafficking in the model organism Saccharomyces cerevisiae). Mentor: Lynne Yenush, Ph.D.
01/09/2009 - 14/09/2011. Master's Degree in Molecular Plant and Cellular Biotechnology at the Universidad Politécnica de Valencia, Valencia (Spain). Regulación del tráfico intracelular de proteínas en levaduras: El papel de las proteínas quinasas Hal4 y Hal5 en el tráfico de permeasas de nutrientes (Regulation of intracellular protein trafficking in yeast: the role of the Hal4 and Hal5 kinases in plasma membrane trafficking). Mentor: LynneYenush, Ph.D.
01/09/2003 - 14/09/2009. 5 year Degree in Agricultural Engineering, Specialization in Biotechnology and Breeding, at the Universidad Politécnica de Valencia, Valencia (Spain). Final year research project at the Albanova Center-Royal Institute of Technology (KTH), Stockholm (Sweden). “Cell and protein stability during surface expression of protein Z in Escherichia coli”. Mentor: Gen Larsson.
1. Primo C, Pizzio G. A., Yang J, Gaxiola R.A., Scholz-Starke J, Hirschi K.D (2019). Plant proton pumping pyrophosphatase: the potential for its pyrophosphate synthesis activity to modulate plant growth. Plant Biol J 2019 May. PMID: 31081197
2. Scholz-Starke J*., Primo C*., Yang J., Kandel R., Gaxiola R.A., Hirschi K.D. (2019) The flip side of the Arabidopsis type I proton-pumping pyrophosphatase (AVP1): Using a transmembrane H+ gradient to synthesize pyrophosphate. J Biol Chem 2019 Jan 294:1290–1299. PMID: 30510138. * Authors contributed equally.
3. Yang J, Elbaz-Younes I, Primo C, Murungi D, Hirschi KD (2018). Intestinal permeability, digestive stability and oral bioavailability of dietary small RNAs. Sci Rep. 2018 Jul 6;8(1):10253. PMID: 29980707.
4. Yang J, Primo C; Elbaz-Younes I, Hirschi KD. (2017) Bioavailability of Transgenic microRNAs in Genetically Modified Plants. Genes Nutr. 2017 Jul 7;12:17. PMID: 29507644.
5. Yang J, Kongchan N, Primo C, Neilson JR, Hirschi KD. (2017) The atypical genesis and bioavailability of the plant-based small RNA MIR2911: bulking up while breaking down. Mol Nutr Food Res. 2017 Sep;61(9). Cover Article. PMID: 28319645.
6. Primo C, Ferri-Blázquez A, Loewith R, Yenush L. (2017) Reciprocal regulation of Target of Rapamycin Complex 1 and potassium homeostasis. J Biol Chem. 2017 Jan 13;292(2):563-574. PMID: 27895122.
7. Mattiazzi UM, Prelec M, Brložnik M, Primo C, Curk T, Ščančar J, Yenush L, Petrovič U. (2015) Yeast Saccharomyces cerevisiae adiponectin receptor homolog Izh2 is involved in the regulation of zinc, phospholipid and pH homeostasis. Metallomics. 2015 Sep;7(9):1338-51. PMID: 26067383.
8. Mulet JM, Llopis-Torregrosa V, Primo C, Marqués MC, Yenush L. (2013) Endocytic regulation of alkali metal transport proteins in mammals, yeast and plants. Curr Genet. 2013 Nov;59(4):207-30. Review. PMID: 23974285.
9. Pérez-Valle J, Rothe J, Primo C, Martínez Pastor M, Ariño J, Pascual-Ahuir A, Mulet JM, Serrano R, Yenush L. (2010) Hal4 and Hal5 Protein kinases are required for general control of carbon and nitrogen uptake and metabolism. Eukaryot Cell. 2010 Dec;9(12):1881-90. PMID: 20952580.