Plants are nature's other successful experiment with multicellular life. To coordinate growth and development of their cells, tissues and organs plants have evolved unique plasma membrane receptor kinases (RKs). Several members of this protein family function as pattern recognition receptors, and as hormone receptors shaping the architecture of the plant. There is mounting evidence that different plant RKs are organized in membrane signaling complexes. RKs have a common structural architecture and share downstream signaling components. As such, it is presently unclear how the recognition of specific endogenous or foreign signals at the cell surface is translated into the activation of specific developmental programs or immune responses in the cytosol. We propose to combine physiology, genetics and cell biology with phosphoproteomics, quantitative biochemistry and structural biology to identify the shared and specific mechanisms by which plant developmental and immune receptor complexes are activated. We will dissect, in molecular detail, how activated receptor complexes generate specific signaling output in the cytosol and how the activity of plant RKs are regulated by inhibitor proteins. We envision that our work will provide a molecular framework for understanding how specificity is encoded at the molecular level in RK signaling, setting the stage for engineering these pathways in crops in the future.

The fruitfly (Drosophila melanogaster) is an important model organism for the studies of normal development and different disease states. It has a relatively small but well annotated genome encoding for approximately 15 000 genes, of which 13500 are protein coding genes. Drosophila has been a successful model organism partly because the great majority (close to 80%) of human disease genes have homologous genes in fruitfly making it a very good model to study various diseases. The rapid life cycle and powerful methods to analyse gene function makes fruitfly an attractive system to study gene function even in a large scale. Understanding the function of each and every gene and protein in an organism is the ultimate goal in biology, and this is likely to be significantly easier to achieve in Drosophila than in human. Currently, depending on the organism, up to half of the genes identified through genome sequencing studies are of unknown function and it is a major challenge in the future to understand the function and interactions of all these genes. Another challenge in biology is to understand how to exploit the gene information to improve human health. There has been intensive research focus on human disease genes, which when mutated lead to disease. However, a disease mutation does not always lead to disease. Furthermore, very often a drug targeting such a disease gene fails to cure the disease due to unexpected effects. Thus we need to learn more about the other genes that are regulating these diseased genes and deciding factors if a disease gene mutation will cause disease. Some of these genes may not have been identified and that is why we need a new tool to identify such disease regulating genes. Genetic research has traditionally used two approaches to study gene function which are complementary in nature. These are decreasing the amount of an expressed gene by mutations or gene silencing or by increasing the expression of the gene with additional copies of the gene. Whereas decreasing the amount of gene expression in a large scale has been relatively easy by generation and utilization of mutant collections or gene silencing, increasing the gene expression has been hampered due to lack of suitable gene collections. We aim to isolate the majority of the Drosophila protein coding genes to form such a large-scale collection of genes, which can be expressed in both cultured cells and in live fruitflies to study the function of these genes in different biological processes such as cell growth and animal development. Such genome-scale collections have been or are being made for other species, including the collections of worm (C. elegans), mouse and human genes, but no collections are available for screens in live animals. Our aim is that the Drosophila gene collection becomes a resource for the whole scientific community. Having a flexible and thoroughly characterized gene collection covering most of the genome would save significant amount of time and resources and enable researchers to enhance their scientific output. This resource would also be important for the identification of new genes regulating disease progression or any other biological processes. Following the tradition in Drosophila research where openness and free distribution of research reagents and clones is promoted, this resource of genes, as plasmids and fly strains, will be made available for all researchers.

The human body encounters a limitless number of potential foreign antigens on a daily basis. How, then, does our body recognize and fend off such foreign invaders before having had any prior exposure to them? An important component of the immune system are B-cells, which produce high affinity antibodies that are highly specific for a given antigen. Instead of encoding individual genes to produce individual antibodies, B-cells evolved the ability to have one specific gene undergo programmed mutagenesis, which leads to large scale genomic rearrangements combined with an extraordinarily high rate of point mutations, where a single base of the DNA is altered, reaching a million-fold above background levels. Paradoxically, however, the same machinery that normally protects our genome from DNA damage is hijacked by B-cells in order to induce these mutagenic alterations. Therefore, unlike all other somatic cells, B-cells are unique in that their development and maturation is dependent on programmed genomic instability. As one may expect, this mutagenic process sometimes results in off-target mutations at non-antibody genes, which can lead to chromosomal instability and compromises the health and well-being of many organisms. One such example is the accumulation of mutations in B-cells leading to the aging of the immune compartment, which has been acquiring increased emphasis as an important driver for organismal ageing. The aim of my research proposal is to understand how DNA repair processes affect the development, maturation, and ageing of B-cells. Our results will have broad implications for the mechanisms underlying antibody diversification, genomic instability, tumorigenesis, and how DNA damage affects cellular and organismal aging.

Studies of adaptive radiations - groups of closely related species adapted to very different conditions - have yielded important insights into our understanding of evolution ever since the pioneering works of Darwin and Wallace. Rapid recent radiations of species can be used as models allowing us to study general evolutionary processes that were at work during the major adaptive radiations in the history of our planet. The conditions under which adaptive radiations occur are not well understood and generally it is not clear why some groups of organisms are very species-rich, while others consist of only few species despite similar age. Adaptive radiations can form in a very short period of time, e.g. species-rich groups of African cichlids are only few thousand years old and speciation rates in such groups is very high, yet general reasons for such rapid ('explosive') speciation require further investigation. This project is devoted to the analysis of evolutionary genetic processes during multiple rapid radiations in a plant genus Lupinus (Leguminosae), which exhibits some of the highest known rates of net diversification in plants. Exceptional rates of species diversification have been documented for Andean lupins, where 85 species have evolved in the last 1.8 million years. An independent lineage of lupins is actively radiating in North America. Such replicate radiations provide powerful comparative systems to address questions about the evolutionary forces driving episodes of diversification. Detailed evolutionary genetic analysis of replicate rapid radiations has not been undertaken previously. Despite relatively low sequence divergence among recently diverged species of Western New World lupins, the range of life forms (from dwarf annuals and prostrate herbs to small trees), and habitats occupied is striking. This accelerated morphological and ecological diversification suggests that many genes may have been under strong adaptive selection. The aim of the project is to address currently unanswered questions about the types of genes involved in adaptation during adaptive radiations as well as the relative roles of selection at the amino acid level versus regulatory regions. This will involve the comparisons of the patterns of DNA sequence divergence and gene expression between closely related and recently diverged species with divergent life forms and adapted to a range of environments. Genome-wide DNA polymorphism/divergence as well as expression data will be obtained by Solexa/Illumina sequencing of cDNA. This will be done for actively radiating clades of species in the Andes and North America as well as for a set of species outside actively radiating clades for comparison.

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.