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’.

More information about Paul van Heusden

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

Publications