Cellular and molecular interactions of glucosinolate-derived isothiocyanates

A PhD position in molecular biology focusing on the cellular and molecular interactions of plant phytochemicals is available at the Department of Biology, NTNU. The fellowship is for three years with the possibility of a fourth year including 25 % teaching duties to the Department of Biology. The position is within the NTNU Cell and Molecular Biology Group (CMB)

Project background:
Plant phytochemicals comprise well known pharmaceuticals and antioxidants like salicylic acid, phenolics, coumarin, flavonoids, digitalis and cyanogenic glycosides, that constitute binary enzyme glucoside systems. They are stored as hydrophilic and inactive prodrugs, and released as lipid soluble aglycones, a principle also used in synthetic drugs. A group of aglycones from glucosinolates, naturally found in cabbage and broccoli, are commonly known as cancer chemopreventive agents; in the human diet found epidemiologically to be anti-carcinogenic. These compounds can both prevent the development of precancerous cells but also selectively trigger cell-death in malignant cells. In many organisms changes in redox status is linked to defence, immune responses and cell death. In mammalian cell-cultures glucosinolate derived aglycones has been shown to have redox-mediated properties that can inhibit carcinogenesis, and alter gene expression through the modulation of thiols and depleting glutathione, but also affect the cell cycle and induce apoptosis.

Considering the importance of these compounds in both human diet, and in the plants themselves, we have for many years investigated the enzyme-system responsible for aglycone release in plants. In Arabidopsis and Brassica plants this system has largely been explored in pathogen and insect defence, both systemically and locally. Rapid release of potent and toxic metabolites occurs when tissue integrity is compromised. The toxic aglycones are reactive sulphur species; isothiocyanates and derivatives that potentially can modulate several cellular targets in-vivo; cytoskeleton, mitochondria, ion channels, and gene-expression, a largely unexplored view of their effects.

The PhD project aims to investigate the interaction of isothiocyanates in both; plants and mammalian cells including laboratory animals, to find common mechanisms of action, with particular emphasis on cell-death, apoptosis, senescence and the cytoskeleton. This will be done by a variety of methods and state-of the art equipment in gene expression profiling and confocal microscopy.

Requirements:
The positions require a Master degree or similar within molecular biology and/or cell biology, alternatively; biotechnology, toxicology/pharmacology or biochemistry. The applicant must be qualified for the doctoral program within these disciplines. Experience from work on Arabidopsis/Brassicas is an advantage, but not an absolute requirement. Candidates with knowledge of one or more of the following methods and techniques will be considered advantageous; animal or plant cell-culture (transfection and transformation), microscopy (confocal and EM), gene expression profiling/DNA-microarray, research-animal certificate (or experience). We will put emphasis on composing a research team with complementary skills, where competence in cell and molecular biology is essential.

We are looking for a hard-working candidate, highly motivated to conduct fundamental scientific research. Ability to carry out goal-oriented work, ability to deliver, oral and written presentation of research results, and good co-operation abilities will be emphasized.

For more information see: UTLYSNINGSTEKST.

Application deadline: 06.11.2009. Reference number: NT-66/09.

Questions regarding the position can be directed to:
Associate Professor Ole Petter Thangstad (ole.thangstad@bio.ntnu.no) tlf. 73 59 60 96.