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Research project (§ 26 & § 27)
Duration : 2018-09-15 - 2021-09-14

Statistics are procedures that combine, organize, and summarize data to extract information. While the collected data are initially unorganized and ‘raw’, statistics allows the organization of the raw data into a condensed and more meaningful structure. This enables the examination and quantification of relationships among variables to show trends and investigate whether a theory or hypothesis is supported by the data. Statistics reaches from simple calculation of mean values and standard deviations to the complex fields of variable selection in high-dimensional data sets and hybrid modelling to integrate many different sources of information into a knowledge base. Biopharmaceutical process development is commonly very empirically driven and needs a large number of experiments delivering corresponding data from diverse analytical tools and monitoring processes. Statistical evaluation of such data to determine precision, accuracy, reproducibility, and robustness of measurements are daily business for all scientists. High throughput methods for screening, process development and analytics were set up and are current routine in many companies. Both lead to an exponential increase of included variables and parameters, and consequently, to huge expansion of the amounts of data. Furthermore, the release of the PAT guidance by the FDA in 2004 as the enabling aspect of Quality-by-Design in biopharmaceutical production changed the perspective on data interpretation including the need for modelling strategies, for predictability and evaluation of data in real time or close to. To address the above-mentioned challenges and needs a collaboration project shall be started between the Process Science Department of BI RCV and BOKU Vienna. It will include a postdoctoral position under the joint supervision of 2 key researchers one with a strong statistics background and the other one with established experience in bioengineering and downstream processing
Research project (§ 26 & § 27)
Duration : 2018-07-01 - 2021-06-30

Clinical and historical data underscore the ability of influenza viruses to ally with certain bacterial species and predispose the host for secondary bacterial infection. Bacterial pneumonia postinfluenza infection was identified as the major cause of mortality during the most devastating influenza pandemics in 1918/19 and 1957/58 with S.aureus and S.pneumoniae being the most commonly associated etiological agents. Vaccination is the best method to prevent infectious disease. There is, however, no S.aureus prophylaxis available and S.pneumoniae vaccines were shown to be largely ineffective. On top, the rise of multi-drug-resistant bacterial strains is alarming. Yet, it was shown that by limiting primary viral infection, influenza vaccines are able to decrease subsequent secondary bacterial infections, leaving influenza vaccines as only promising measure to prevent secondary bacterial complications. Low cross-reactivity of current influenza vaccines, however, still enables drifted influenza strains to cause disease and may prime patients for difficult-to-treat bacterial superinfections. Several viral and host key players have been identified to increase susceptibility of the host for postinfluenza secondary infection. The influenza neuraminidase was shown to increase bacterial adherence to epithelial tissues, by unmasking and up-regulating expression of cellular receptors. The viral proteins PB1-F2 and NS1 may suppress the host innate bacterial responses by modulating the host interferon response and dysregulating cytokine and chemokine secretion. Current influenza vaccines are standardized as per their hemagglutinin content and the amount of other viral proteins present is predefined by their natural abundance in the influenza virion. This leaves the influenza NA and (to an even higher degree) the NS1 largely underrepresented in current vaccines, whereas PB1-F2 is even absent. We aim to supplement/enrich a virus-like particle preparation based on the influenza HA and a non-influenza capsid protein with these antigens at different ratios compared to the HA. These preparations will be evaluated for their beneficial contribution in protective efficacy against S.aureus and S.pneumoniae infections after heterologous influenza infection; mimicking the situation of vaccine mismatch.
Research project (§ 26 & § 27)
Duration : 2018-05-01 - 2021-04-30

We found previously that lack of a specific m5C methylation on 28S ribosomal RNA conferred by Nsun5 leads to increased lifespan and stress resistance of yeast, worms and flies. However, if Nsun5 or any other RNA methyltransferase is also capable of modulating healthy lifespan of mammals is not known. Thus, the aims of this project encompass the measurement of the lifespan of a Nsun5 constitutive whole-body knockout mouse model compared to littermate controls, as well as phenotypic evaluation of health that we hypothesize to be improved by Nsun5 knockout at advanced age. Mice of both sexes in a C57BL6/J background will be tested. We further hypothesize that loss of Nsun5 also increases stress resistance on cellular level and alters ribosome function. This hypothesis will be tested by characterization of Nsun5 activity in different tissues and at different timepoints during the lifespan, assessment of cellular fitness by measurement of stress resistance in-vitro, as well as translation rate and fidelity. We will further isolate mRNAs contained in ribosomes by immunoprecipitation utilizing the ribo-tag platform, and compare their expression to total cellular mRNAs. Thereby we will be able to identify global gene expression patterns of translational regulation and confirm the presence of similar regulatory elements as we found in yeast, such as upstream open reading frames. Due to the high evolutionary conservation of Nsun5, we are convinced that conclusions obtained within this project are also applicable to humans. Thus, the experiments proposed here will contribute to a better understanding of the contribution of ribosomal RNA methylation to organismal fitness and probably pave the ground for the design of healthspan extending strategies in humans.

Supervised Theses and Dissertations