Paul van Heusden
Assistant professor
- Name
- Dr. G.P.H. van Heusden
- Telephone
- +31 71 527 4996
- g.p.h.van.heusden@biology.leidenuniv.nl
- ORCID iD
- 0000-0002-6422-8034
I am using the yeast Saccharomyces cerevisiae to investigate fundamental biological processes. Currently, my major research themes are ‘Signal transduction processes in yeast involving 14-3-3 proteins’ and ‘The mechanism of Agrobacterium-mediated transformation of eukaryotic cells’.
I am using the yeast Saccharomyces cerevisiae to investigate fundamental biological processes. Currently, my major research themes are ‘Signal transduction processes in yeast involving 14-3-3 proteins’ and ‘The mechanism of Agrobacterium-mediated transformation of eukaryotic cells’.
1. Signal transduction processes in yeast involving 14-3-3 proteins
14-3-3 proteins form a family of highly conserved proteins that can bind hundreds of different intracellular proteins. In this way, the 14-3-3 proteins regulate the activity of enzymes, regulate the subcellular localization of proteins and stimulate protein-protein interactions. These activities are important for many cellular processes like apoptosis, the cell cycle, stress response and signal transduction. 14-3-3 proteins are related to a number of human diseases like cancer and neurological diseases as Parkinson’s disease, the Miller-Dieker syndrome and Alzheimer’s disease and are used in a diagnostic test for BSE (mad cow disease). We use the yeast S. cerevisiae to study fundamental aspects of 14-3-3 proteins. This organism has two genes encoding 14-3-3 proteins, BMH1 and BMH2. As in higher eukaryotes, the S. cerevisiae 14-3-3 proteins are involved in many cellular processes and many different binding partners have been identified.
At the moment we mainly focus on the role of 14-3-3 proteins in cation homeostasis. We especially investigate the role of 14-3-3 proteins involved in signal transduction processes involved in potassium and phosphate uptake.
2. The mechanism of Agrobacterium-mediated transformation of eukaryotic cells
The soil bacterium Agrobacterium tumefaciens is capable of transferring part of its tumor-inducing (Ti) plasmid, the T-DNA, to plant cells, where it stably integrates into the host genome causing grown gall disease. This property is exploited in biotechnology to use Agrobacterium to generate transgenic plants. In the laboratory Agrobacterium can also transform non-plant species like fungi and yeasts. Therefore, the yeast S. cerevisiae can be used to investigate the transformation process.
The Agrobacterium system delivers a single-stranded (ss) DNA molecule with at the 5’-end the pilot protein VirD2 into host cells through a type 4 secretion system (T4SS). The nuclear localization sequence in VirD2 guarantees a rapid translocation into the nucleus of the host cells. Besides the T-strand-VirD2 complex, the T4SS is used also to secrete separately a set of virulence proteins into the host cells. The latter are effector proteins that aid in the transformation process. For instance, the VirE2 protein is an ssDNA binding protein which coats (and thus protects) the T strand on its way to the nucleus and VirF, an F-box protein, that is thought to help in the integration process by uncoating the T-DNA. Host factors also play an important role in Agrobacterium-mediated transformation. In a number of projects we use S. cerevisae to investigate the interplay between Agrobacterium virulence proteins and host proteins to understand the molecular mechanism of the transformation process.
Brief Biography
- 1990 - : Assistant Professor at Leiden University
- 1987 - 1990: Post-doctoral Fellow, Utrecht University - Principal investigator: Karel Wirtz
- 1985 - 1987: Post-doctoral Fellow, University of Texas Medical School at Houston, US - Principal investigator: William Dowhan
- 1982 - 1984: Post-doctoral Fellow, Utrecht University - Principal investigator: Karel Wirtz
- 1978 – 1982: PhD-student at Utrecht University - Promotor: Henk van den Bosch
Thesis: ‘The biosynthesis of dipalmitoylphosphatidylcholine in rat lung. Studies on remodeling mechanisms and de novo synthesis.’
- 1972 - 1978: Chemistry study at Utrecht University
Assistant professor
- Science
- Instituut Biologie Leiden
- IBL Plant Sciences
- Shao S., Heusden G.P.H. van & Hooykaas P.J.J. (2019), Complete sequence of succinamopine Ti-plasmid pTiEU6 reveals its evolutionary relatedness with nopaline-type Ti-plasmids, Genome Biology and Evolution 11(9): 2480-2491.
- Roushan M.R., Zeeuw M.A.M. de, Hooykaas P.J.J. & Heusden G.P.H. van (2018), Application of phiLOV2.1 as a fluorescent marker for visualization of Agrobacterium effector protein translocation, Plant Journal 96(3): 685–699.
- Hooykaas P.J.J., Heusden G.P.H. van, Niu x., Roushan M.R., Soltani J., Zhang X. & Zaal E.J. van der (2018), Agrobacterium-mediated transformation of yeast and fungi. In: Gelvin S. (Ed.) Agrobacterium Biology. Current Topics in Microbiology and Immunology no. CTMI 418 Cham: Springer. 349-374.
- Shao S., Zhang, X., Heusden G.P.H. van & Hooykaas P.J.J. (2018), Complete sequence of the tumor-inducing plasmid pTiChry5 from the hypervirulent Agrobacterium tumefaciens strain Chry5, Plasmid 96-97: 1-6.
- Jansen H., Dirks R.P., Liem M., Henkel C.V., Heusden G.P.H van, Lemmers R.J.L.F., Omer T., Shai S., Punt P.J. & Spaink H.P. (2018), De novo whole-genome assembly of a wild type yeast isolate using nanopore sequencing, F1000Research 6: 618.
- Zhang X., Heusden G.P.H. van & Hooykaas P.J.J. (2017), Virulence protein VirD5 of Agrobacterium tumefaciens binds to kinetochores in host cells via an interaction with Spt4, PNAS 114(38): 10238-10243.
- Teunissen J.H.M., Crooijmans M.E., Teunisse P.P.P. & Heusden G.P.H. van (2017), Lack of 14-3-3 proteins in Saccharomyces cerevisiae results in cell-to-cell heterogeneity in the expression of Pho4-regulated genes SPL2 and PHO84, BMC Genomics 18(1): 701.
- Hermans N., Huisman J.J., Brouwer T.B., Schachner C., Heusden G.P.H., Griesenbeck J. & Noort S.J.T. van (2017), Toehold-enchanced lna probes for selective pull down and single-molecule analysis of native chromatin, Scientific Reports 7: 16721.
- Llopis-Torregrosa V., Ferri-Blazquez A., Adam-Artigues A., Deffontaines E., Heusden G.P.H. van & Yenush L. (2016), Regulation of the Yeast Hxt6 Hexose Transporter by the Rod1 alpha-Arrestin, the Snf1 Protein Kinase, and the Bmh2 14-3-3 Protein, JOURNAL OF BIOLOGICAL CHEMISTRY 291(29): 14973-14985.
- Niu X., Zhou M., Henkel C.V., Heusden G.P.H. van & Hooykaas P.J.J. (2015), The Agrobacterium tumefaciens virulence protein VirE3 is a transcriptional activator of the F-box gene VBF., The Plant journal : for cell and molecular biology 84(5): 914-24.
- Wolterink-van Loo S., Escamilla Ayala A.A., Hooykaas P.J.J. & Heusden G.P.H. van (2015), Interaction of the Agrobacterium tumefaciens virulence protein VirD2 with histones., Microbiology (Reading, England) 161(Pt 2): 401-410.
- Sakalis P.A. & Heusden G.P.H. van; Hooykaas P.J.J. (2014), Visualization of VirE2 protein translocation by the Agrobacterium type IV secretion system into host cells, MicrobiologyOpen 3(1): 104-117.
- J. Ariño; E. Aydar; S. Drulhe; D. Ganser; J. Jorrin; M. Kahm; F. Krause; S. Petrezselyova; L. Yenush; O. Zimmermannova; G.P.H. van Heusden; M. Kschischo; J. Ludwig; C. Palmer; J. Ramos; H. Sychrova (2014), Systems biology of monovalent cation homeostasis in yeast: The translucent contribution, Adv. Micorb Physiol 64: 1 - 63.
- Anemaet I.G. & Heusden G.P.H. van (2014), Transcriptional response of Saccharomyces cerevisiae to potassium starvation, BMC Genomics 15: 1040.
- Zahradka J., Heusden G.P.H. van & Sychrova H. (2012), Yeast 14-3-3 proteins participate in the regulation of cell cation homeostasis via interaction with Nha1 alkali-metal-cation/proton antiporter., Biochimica et Biophysica Acta 1820(7): 849-858.
- Dietvorst J., Walsh M.C., Heusden G.P.H. van & Steensma H.Y. (2010), Comparison of the MTT1- and MAL31-like maltose transporter genes in lager yeast strains, FEMS Microbiology Letters 310(2): 152-157.
- Dietvorst J., Walsh M.C., Heusden G.P.H. van & Steensma H.Y. (2010), Comparison of the MTT1- and MAL31-like maltose transporter genes in lager yeast strains., FEMS Microbiology Letters 310: 152-157.
- Gerber S., Hasenbrink G.P.H., Hendriksen W., Heusden G.P.H. van, Ludwig J., Klipp E. & Lichtenberg-Fraté H. (2010), Graphical analysis and experimental evaluation of Saccharomyces cerevisiae P_TRK1|2 and P_BMH1|2 promoter region. In: DeLisi C., Kanehisa M., Klipp E., Miyano S., Mohr S., Wallach I. (Eds.) Genome Informatics 2009. no. 22: World Scientific. 11-20.
- Heusden G.P.H. van (2009), 14-3-3 proteins: insights from genome-wide studies in yeast, Genomics 94: 287-293.
- Soltani J., Heusden G.P.H. van & Hooykaas P.J.J. (2009), Deletion of host histone acetyltransferases and deacetylases strongly affects Agrobacterium-mediated transformation of Saccharomyces cerevisiae, FEMS Microbiology Letters 298(2): 228-233.
- Gerber S., Hasenbrink G., Hendriksen W.T., Heusden G.P.H. van, Ludwig J., Klipp E. & Lichtenberg-Fraté H. (2009), Graphical analysis and experimental evaluation of Saccharomyces cerevisiae Ptrk1/2 and Pbmh1/2 promoter region, Genome Informatics 22: 11-20.
- Bruckmann A., Hensbergen P.J., Balog C.I., Deelder A.M., Brandt R., Snoek I.S.I., Steensma H.Y. & Heusden G.P.H. van (2009), Proteome analysis of aerobically and anaerobically grown Saccharomyces cerevisiae cells, J Proteomics 71: 662-669.
- Soltani J., Heusden G.P.H. van & Hooykaas P.J.J. (2008), Agrobacterium-mediated transformation of non-plant organisms. In: T.Tzfira and V. Citovsky (Ed.) Agrobacterium: from biology to biotechnology. New York: Springer Press. 649-675.
- Bruckmann A., Hensbergen P.J., Balog C.I.A., Deelder A.M., Brandt R., Snoek I.S.I., Steensma H.Y. & Heusden G.P.H. van (2008), Proteome analysis of aerobically and anaerobically grown Saccharomyces cerevisiae cells, J Proteomics 71(6): 662-669.
- Heusden G.P.H. van & Steensma H.Y. (2008), The Saccharomyces cerevisiae Wss1 protein is only present in mother cells, FEMS Microbiology Letters 282: 100-104.
- Hooykaas P.J.J., Dulk H. den, Bundock P., Soltani J., Attikum H. van & Heusden G.P.H. van (2006), Agrobacterium Protocols: Transformation of Yeast (Saccharomyces cerevisiae). In: Wang K. (Ed.) Agrobacterium Protocols. Methods in Molecular Biology no. 344 Totowa: Humana Press. 465-473.
- Heusden G.P.H. van & Steensma H.Y. (2006), Yeast 14-3-3 proteins, Yeast 23: 159-174.
- Heusden G.P.H. van (2005), proteins:Regulators of numerous eukaryotic proteins, Life 57: 623-629.
- Bruckmann A., Steensma H.Y., Teixera de Mattos M.J. & Heusden G.P.H. van (2004), Regulation of transcription by Saccharomyces cerevisiae 14-3-3 proteins, Biochemical Journal 382: 867-875.
- Hemert M.J. van, Deelder A.M., Molenaar C., Steensma H.Y. & Heusden G.P.H. van (2003), Self-association of the spindle pole body-related intermediate filament protein Fin 1p and its phosphorylation-dependent interaction with 14-3-3 proteins in yeast, Journal of Biological Chemistry 278(17): 15049-15055.
- Hemert M.J. van, Lamers G.E.M., Klein D.C.G., Oosterkamp T.H., Steensma H.Y. & Heusden G.P.H. van (2002), The Saccaromyces cerevisiae Fin1 protein forms cell cycle-specific filaments between spindle pole doies, 99: 5390-5393.
- Hemert M.J. van, Lamers G.E.M., Klein D.C.G., Oosterkamp T.H., Steensma H.Y. & Heusden G.P.H. van (2002), The Saccharomyces cerevisiae Fin 1 protein forms cell cycle-specific filaments between yeast spindle pole bodies, Proceedings of the National Academy of Sciences of the United States of America 99: 5390-5393.
- Knetsch M.L.W., Heusden G.P.H. van, Ennis H.L., Shaw D.R., Epskamp S.J.P. & Snaar-Jagalska B.E. (1998), Isolation of a Dictyostelium discoideum 14-3-3 homologue which can replace the essential yeast BMH1 and BMH2 genes, Biochimica et Biophysica Acta : Molecular Cell Research 1357(2): 243-248.
- Heusden G.P.H. van, Nebohacova M., Overbeeke T.L.A. & Steensma H.Y. (1998), The Saccharomyces cerevisiae TGL2 gene encodes a protein with lipolytic activity and can complement an Escherichia coli diacylglycerol kinase disruptant, Yeast 14: 225-232.
- Heusden G.P.H. van, Zanden L.A. van der, Ferl R.J. & Steensma H.Y. (1996), Four Arabidopsis thaliana 14-3-3 protein isoforms can complement the lethal yeast BMH1 BMH2 double disruption, FEBS Letters 391(3): 252-256.
- Heusden G.P.H. van, Griffiths D.J.F., Ford J.C., Chin-A-Woeng T.F.C., Schrader P.A.T., Carr A.M. & Steensma H.Y. (1995), The 14-3-3 proteins encoded by the BMH1 and BMH2 genes are essential in the yeast saccharomyces-cerevisiae and can be replaced by a plant homolog, European Journal of Biochemistry 229(1): 45-53.
- Lu G., Vetten N.C. de, Sehnke P.C., Isobe T., Ichimura T., Fu H., Heusden G.P.H. van & Ferl R.J. (1994), A single Arabidopsis GF14 isoform possesses biochemical characteristics of diverse 14-3-3-homologs, Plant Molecular Biology 25(4): 659-667.
- Heusden G.P.H. van, Koning W.J. de, Aart Q.J.M. van der, Berg J.A. van den & Steensma H.Y. (1993), The nucleotide-sequence of a 2.1 KB fragment from chromosome-VI of saccharomyces-cerevisiae identifies a trna(gly) gene, part of a delta-element and a palindromic , Yeast 9(10): 1107-1110.
- Castro Cabezas M., Heusden G.P.H. van, Bruin T.W.A. de, Beckhoven J.R.C.M. van, Kock L.A.W., Wtrtz K.W.A. & Erkelens D.W. (1993), Reverse cholesterol transport - relationship between free-cholesterol uptake and HDL3 in normolipidemic and hyperlipemic subjects, European Journal of Clinical Investigation 23(2): 122-129.
- Heusden G.P.H. van, Beckhoven J.R.C.M. van, Thieringer R., Raetz C.R.H. & Wirtz K.W.A. (1992), Increased cholesterol-synthesis in Chinese-hamster ovary cells deficient in peroxisomes , Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism 1126(1): 81-87.
- Heusden G.P.H. van, Wenzel T.J., Lagendijk E.L., Steensma H.Y. de & Berg J.A. van den (1992), Characterization of the yeast BMH1 gene encoding a putative protein homologous to mammalian protein kinase-II activators and protein-kinase-c inhibitors , FEBS Letters 302(2): 145-150.
- Haren L. van, Teerds K.J., Ossendorp B.C., Heusden G.P.H. van, Orly J., Stocco D.M., Wirtz K.W.A. & Rommerts F.F.G. (1992), Sterol carrier protein-2 (nonspecific lipid transfer protein) is localized in membranous fractions of Leydig-cells and Sertoli cells but not in germ-cells , Biochimica et Biophysica Acta 1124(3): 288-296.
No relevant ancillary activities