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Synopsis

  Conflict between organisms, a powerful driving force in evolution, has led to the appearance of a variety of immune systems on earth. In eukaryotes, certain key elements of these immune systems appear to be deeply conserved. Vertebrates, invertebrates and plants all have the ability to recognise and respond to conserved molecules which typify various classes of invader (bacteria, fungi etc). The biological success of plants (ie. their biomass and their high diversity) is remarkable given that, in addition to their numerous microbial pathogens, they are prey to many of the largest extant group of animals, the arthropods. The plant immune system provides direct protection against invaders and can also attract body guards in the form of predatory insects. Both these facets of the defense response (‘direct’ and ‘indirect’ defense) are controlled exquistitely.

  Our laboratoy has a long standing interest in regulatory mechanisms in the plant immune system. We believe that lipid signaling is central to the plant immune system and may also extend to the regulation of genes involved in abiotic stress. In particular we are interested in the role of oxygenated fatty acid-derivatives (oxylipins) in the regulation of defense gene expression in response response to wounding and pathogenesis. Of primary interest to us is the jasmonate family of regulators. Many other oxylipins exist in plants but we know relatively little about the functions of these molecules. We believe that different oxylipins act together as regulators allowing the fine control of defense gene expression in response to attack (and, perhaps, gene expression in response to other inputs). We termed the changing balance of different oxylipins the 'oxylipin signature'. We believe that the oxylipin signature may allow fine tuning of gene expression helping the organism to distinguish between different insults and to respond to a changing environment. A study of the roles of oxylipins may yield unique insights into how inducible gene expression is regulated in pathogenesis and wounding. Much of our research is aimed at testing these notions and understanding the place of the oxylipin signature in plant defense gene regulation.

  Before various organisms came into conflict with one another they had to cope with potentially hostile environments. It is thus to be expected that environmental stress responses are ancient and deeply conserved. Many stresses, both abiotic and biotic, can lead to oxidative membrane damage and fragmentation of fatty acids. We found that a,b-unsaturated carbonyl groups in fatty acid derivatives can confer potent regulatory effects on gene expression in both the immune system and on abiotic stress responses.These compounds are reactive electrophile species (RES), a class of molecules of great interest to our group. Of central interest to us is the 3-carbon compound malondialdehyde (MDA). This well-known molecule can powerfully upregulate many environmental stress genes and may represent an ancient signal compound. A simple protocol we established for the volatilization of MDA has proven very useful in our initial studies to investigate the compounds’ potent biological activites. MDA is a ubiquitous compound much of which is derived in vivo in plants from tri-unsaturated fatty acids. A levels estimated to be between 2.5 and 5.5 nmol per gram fresh weight, MDA levels in healthy leaves are considerable. The molecule can be found in both free form (at about 1 nmol per gram fresh weight) and in bound form (approximatley 2 to 4 nmol per gram fresh weight). The high level of free MDA might be especially significant. In the cytosol it is expected to be present as the charged and relatively unreactive enolic ion. But upon cell damage, or lowering of pH in response to pathogen recognition, generation of the highly reactive b-hydroxyacrolein and dialdehyde forms may generate potent signals. MDA is thus a highly relevant candidate in signaling nonenzymatic lipid damage in response to stress.

  In addition, we are creating several tools to allow the global automated annotation of defense genes in Arabidopsis thaliana. This on-going project uses annotation data mining, comparative BLASTs and a controlled vocabulary. A goal is to be able to estimate the number of genes that function in the immune system of Arabidopsis.

  The research group is multinational and includes postdocs, graduate students, diploma students and technicians. We are frequently visited by researchers from overseas. The group has a publication record in biochemical (metabolite profiling) and molecular (cDNA microarrays) approaches. These approaches are combined with the analysis of mutants in signal transduction. Our work has contributed to understanding the biology of jasmonates, divinyl ethers and electrophilic lipids containing double bond-conjugated carbonyl groups and, more generally, to the regulation of inducible defense genes.

Some of the group's publications, including those cited below, are listed at this site.

Research Strategies

  Biologically active lipids play roles in development, reproduction, pathogenesis, inflammation, intra- and intercellular signaling and, interspecific communication. In animals leukotrienes and prostaglandins represent well known representatives of such molecules. A growing number of biologically active fatty acid-derived compounds have been characterized in plants. These include jasmonates which play critical roles in defense and development. Many other biologically active lipids remain to be characterized in plants. To identify and characterize them requires powerful biochemical approaches and to identify their biological activity requires tools for the global analysis of gene expression as well as mutants. Using a combination of genetics, biochemistry, and gene expression analysis we have recently found several new oxylipins in plants.

  To investigate the biogenesis and function of oxylipins and other lipids during wounding and pathogenesis. We developed a method for the global analysis and quantitation of oxylipins in tissues. This 'oxylipin signature' method involves extraction and gas chromatography-mass spectroscopic analysis of the oxylipin pool. The results yield 'oxylipin signatures' which reflect the physiological status of the tissue in question. The method has been applied to study the jasmonic acid family of regulators. Dramatic changes in the oxylipin signature arise when tissues are wounded or infected (Weber et al., 1997; 1999; Vollenweider et al, 2000). In parallel, we have developed a rapid in vitro assay with which to assay the levels of enzymes involved in oxylipin metabolism (Caldelari and Farmer, 1998). This assay is useful since it requires only minute amounts of plant tissue (eg. 1 ml of leaf or root juice).

  We are using both small dedicated and genome-scale cDNA microarrays for the analysis of global gene expression in Arabidopsis. These arrays are being used chiefly to dissect the roles of oxylipins and electrophiles in defense and stress gene regulation. We are also using the arrays to search for novel biologically active oxylipins. Both microarrays and oxylipin profiling generate large quantities of information. We employ a relational open source database (Nomad database) and create new tools in an ongoing effort to provide over thorough and statistically robust analysis of data. A 'full genome' (25k) Arabidopsis microarray should be in routine use in the group by April 2004.

Spin-offs

A full understanding of plant defense strategies and signal transduction routes can and has lead to the development of alternatives to 'traditonal' pesticides.

Hiring opportunities

  In general postdocs coming to the laboratory have best chances of being hired if they have a stipend. The laboratory is particularly interested in candidates with strong backgrounds in lipid biochemistry or forward genetics.

Funding

Swiss National Science Foundation, Leenaards Foundation, Sandoz Foundation, E. Rub Foundation, Herbette Foundation, 450th Anniversary Foundation, Vaud Academic Society etc.