Research

Magnesium is an essential component of chlorophyll for plant physiology. Low Mg content in the leaves of grapevines reduces photosynthesis and, thus, glucose production and, consequently, lower wine quality. The right choice of rootstock is essential to alleviate this deficiency. However, the necessary Mg efficiency restricts the selection of the rootstocks, and in particular, the rootstocks that have been tried and tested in this country are less suitable. The deficiency can also be remedied by fertilizing the leaves, at least in the short term. But, the most sustainable solution would be to plant clones with an unproblematic Mg metabolism. An important grape variety for Austrian viticulture is mainly affected by Mag deficiency, namely Welschriesling (WR). The WR clones that are available for domestic viticulture all show more or less a weak Mg uptake. The variety has been used in viticulture for several centuries and was intensively cultivated and therefore exists in different genetic types. Since the old descriptions do not report this Mg deficiency, it is entirely conceivable that there is genomics in old genotypes that show average Mg utilization. Therefore, it would be necessary to look for genotypes that offer a better uptake and research it genetically. It is well known that crop phenotypic variation is shaped by their ancestors’ genetic variation and the selection and maintenance of collections of mutations. Moreo ver, most of this varia ti on is quan ti ta ti ve. Therefore, more than ever, an essential goal of genetics is to identify and use appropriate bio-markers for selection. In this way, appropriate biomarkers could be developed for the selection of WR, which enables a distinction between Mg-efficient and inefficient, which is very important for winegrowers. New clones with Mg efficiency would strengthen the local vine nurseries and viticulture and could also mean that vine material can be delivered to the neighbouring countries Hungary, Croa tia, Slovenia and Slovakia because the problem also exists there. Furthermore, this would result in a competitive advantage for domestic planting stock companies.

Theoretical framework One of the first specific defense mechanisms against invading pathogens and self-antigens is the complement system, activated by immunoglobulins (Igs). Igs bind specifically to the antigen on the pathogen and thereby enable the docking of the C1q-complement initiation complex. Two factors influencing the complement activation were so far not investigated in detail. First, the format of the antigen, described by the chemical nature, the molecular size and the mode of presentation (as soluble substance or embedded in vesicles for mimicking the cell surface). Second, the huge difference in complement activation resulting from the degree of oligomerization of the IgMs. Objectives The overall goal of the pent/hexIgM project is to elucidate the activation sites of C1q and the IgM-Fc after binding of pentameric and hexameric IgMs to different antigen formats. Approach/methods We will produce recombinant IgMs and the C1q protein in mammalian cells and generate mutants thereof by yeast surface display. Next, we will confirm the biological activities of generated proteins in vitro by immunochemical and biophysical analyses as well as functionality tests. Most important, we will elucidate in influence of the antigen format and the degree of oligomerization of the IgMs (pentameric versus hexameric IgMs) on the activation of the complement system. Level of originality Although IgMs in combination with complement proteins have an important function in the human body, these proteins are not yet widely used in therapy and diagnosis. The results of the pent/hexIgM project will contribute to understanding the complex mechanisms underlying the activation of the complement cascade and will provide data of particular importance for developing new diagnostics and efficient treatment methods for various infectious, inflammatory, chronical and cancerous diseases.

Development of a process to produce recombinant Influenza Neuraminidase (rNA) antigen in the baculovirus system, and especially downstream processing/purification will be performed in collaboration between the Icahn School of Medicine at Mount Sinai and the University of Natural Resources and Life Sciences to optimize an affinity purification-based downstream process for production of his-tagged rNA which can be successfully implemented at the CMO Expression Systems to produce enough rNA for a Collaborative Influenza Vaccine Innovation Centers (CIVICs) phase I clinical trial. Furthermore, to develop a high-yielding tag-less purification process that would allow us to get sufficient protein yields for post-phase I clinical development and lastly, to perform testing of alternative rNA expression constructs and expression systems. Doing this work will enable us to test rNA vaccines in clinical trials and may also provide a commercial path forward for rNA protein-based vaccine development in general.