ERC FUNDED PROJECTS

Vaccines and immunodiagnostics have been vital for public health and medicine, however a quantitative molecular understanding of vaccine-induced antibody responses is lacking. Antibody research is currently going through a big-data driven revolution, largely due to progress in next-generation sequencing (NGS) and bioinformatic analysis of antibody repertoires. A main advantage of high-throughput antibody repertoire analysis is that it provides a wealth of quantitative information not possible with other classical methods of antibody analysis (i.e., serum titers); this information includes: clonal distribution and diversity, somatic hypermutation patterns, and lineage tracing. In preliminary work my group has established standardized methods for antibody repertoire NGS, including an experimental-bioinformatic pipeline for error and bias correction that enables highly accurate repertoire sequencing and analysis. The overall goal of this proposal will be to apply high-throughput antibody repertoire analysis for quantitative vaccine profiling and discovery of next-generation immunodiagnostics. Using mouse subunit vaccination as our model system, we will answer for the first time, a fundamental biological question within the context of antibody responses - what is the link between genotype (antibody repertoire) and phenotype (serum antibodies)? We will expand upon this approach for improved rational vaccine design by quantitatively determining the impact of a comprehensive set of subunit vaccination parameters on complete antibody landscapes. Finally, we will develop advanced bioinformatic methods to discover immunodiagnostics based on antibody repertoire sequences. In summary, this proposal lays the foundation for fundamentally new approaches in the quantitative analysis of antibody responses, which long-term will promote the development of next-generation vaccines and immunodiagnostics.

1 492 586 €

Start date: 2016-06-01, End date: 2021-05-31

The two fundamental challenges of this project are the integration of medieval Jewries and their histories within the framework of European history without undermining their distinct communal status and the creation of a history of everyday medieval Jewish life that includes those who were not part of the learned elite. The study will focus on the Jewish communities of northern Europe (roughly modern Germany, northern France and England) from 1100-1350. From the mid-thirteenth century these medieval Jewish communities were subject to growing persecution. The approaches proposed to access daily praxis seek to highlight tangible dimensions of religious life rather than the more common study of ideologies to date. This task is complex because the extant sources in Hebrew as well as those in Latin and vernacular were written by the learned elite and will require a broad survey of multiple textual and material sources. Four main strands will be examined and combined: 1. An outline of the strata of Jewish society, better defining the elites and other groups. 2. A study of select communal and familial spaces such as the house, the synagogue, the market place have yet to be examined as social spaces. 3. Ritual and urban rhythms especially the annual cycle, connecting between Jewish and Christian environments. 4. Material culture, as objects were used by Jews and Christians alike. Aspects of material culture, the physical environment and urban rhythms are often described as “neutral” yet will be mined to demonstrate how they exemplified difference while being simultaneously ubiquitous in local cultures. The deterioration of relations between Jews and Christians will provide a gauge for examining change during this period. The final stage of the project will include comparative case studies of other Jewish communities. I expect my findings will inform scholars of medieval culture at large and promote comparative methodologies for studying other minority ethnic groups

1 941 688 €

Start date: 2016-11-01, End date: 2021-10-31

From testicular grafting (1920s) to step counting watches (2014), the perceptions and practices of health seeking individuals have been marked by continuities and profound changes during a twentieth century largely shaped by the advent of a communication society. Visuals can be a source to understand transformations by postulating an interactive, performative power of mass media in societies. Which roles did visuals play in changes from public health and human capital collective understandings of the healthy self to new (sometimes debated) perceptions and practices of our bodies as forms of individual capital in an increasing market-economized world? Pursuing these questions, the project focuses on four fields of investigation -food/nutrition; movement/exercise/sports; sexuality/reproduction/infants and dependency/addiction/overconsumption- in Germany, France and Great Britain studied with an entangled history framework. Within this scope the project aims at understanding (1)how visuals shape our health related self-understandings and practices in a continuity/discontinuity from the bio-political to the bio-economic logic. (2) The project will explore and explain how and why understandings of body capital differ or overlap in European countries. (3) The project will analyse if and how visual media serve as a promotion-communication hyphen for twentieth century preventive-self understanding. With a visual perspective on a long twentieth century, the project seeks to better understand changes and continuities in the history of health intertwined with the history of media. This will provide new insights into how the internalization of bodycapital has evolved throughout the past century, how transformations in the media world (from film to TV to internet) play out at the individual level and how health challenges and cultural differences in body perceptions and practices persist in producing social distinction in an age of global information and advanced health systems.

2 492 124 €

Start date: 2016-09-01, End date: 2021-08-31

"Translational research aims at applying mechanistic understanding in the development of "precision medicine", which depends on precise diagnostic tools and therapeutic approaches. Cancer therapy is experiencing a switch from non-specific, cytotoxic agents towards molecularly targeted and rationally designed compounds with the promise of greater efficacy and fewer side effects. The two cell-cycle kinases CDK4 and CDK6 normally facilitate cell-cycle progression but are abnormally activated in certain cancers. CDK6 is up-regulated in hematopoietic malignancies, where it is the predominant cell-cycle kinase. The importance of CDK4/6 for tumor development is underscored by the fact that the US FDA selected inhibitors of the kinase activity of CDK4/6 as "breakthrough of the year 2013". Our recent findings suggest that the effects of the inhibitors may be limited as CDK6 is not only involved in cell-cycle progression: ground-breaking research in my group and others has shown that CDK6 is involved in regulation of transcription in a kinase-independent manner thereby driving the proliferation of leukemic stem cells and tumor formation. We have now identified mutations in CDK6 that convert it from a tumor promoter into a tumor suppressor. This unexpected outcome is accompanied by a distinct transcriptional profile. Separating the tumor-promoting from the tumor suppressive functions may open a novel therapeutic avenue for drug development. We aim at understanding which domains and residues of CDK6 are involved in rewiring the transcriptional landscape to pave the way for sophisticated inhibitors. The idea of turning a cancer cell's own most potent weapon against itself is novel and would represent a new paradigm for drug design. Finally, the understanding of CDK6 functions in tumor promotion and maintenance will also result in better patient stratification and improved treatment decisions for a broad spectrum of cancer types."

2 497 520 €

Start date: 2016-09-01, End date: 2021-08-31