Life originally emerged and flourished in hydrogen sulfide (H2S)-rich environment and literature published in the past decade started to recognize that H2S is a mediator of many physiological and pathological processes. Exposure to H2S can put animals into suspended animation-like state while the lifespan extensions by the dietary restriction are caused by H2S accumulation. Disturbances in its production are linked to the development of neurodegenerative diseases and cancer, among many others. A new post-translational modification (PTM) of cysteine residues called protein persulfidation (i.e., converting cysteine residues PSH to persulfides, PSSH) has been suggested as a unifying mechanism behind all these effects. Therefore, an understanding of protein persulfidation has not only a fundamental potential, e.g. unraveling new signaling pathways, but also a pharmacological potential in fighting aging and diseases. However, the underlying mechanisms of H2S-mediated PSSH formation are still unclear, mainly due to the lack of a reliable and selective methodology for PSSH labeling. Here, using cutting-edge methodology for PSSH labeling developed by our team, combined with proteomics, metabolomics and molecular biology, and by working on different model systems (cells, C. elegans, rodents) we intend to (i) gain high-resolution structural, functional, quantitative, and spatio-temporal information on PSSH dynamics and position this evolutionary conserved PTM in the global cell signalling scheme, particularly in relation to other cysteine PTMs, (ii) understand the intricate relation between aging and PSSH and (iii) identify the protein targets whose change of function by persulfidation is implicated in aging and disease progression. The ultimate objective is to pave the way for the development of innovative therapeutic strategies that will permit targeted redox control of cell metabolism, and delay aging and disease progression.

Over the past ten years, 3D bioprinting has emerged as a powerful tool to fabricate human tissue models ex vivo. These models can be used for drug discovery, to obtain a better understanding of physiological and pathological mechanisms, and in the future to replace diseased or injured tissues and organs. To successfully fabricate functional tissues, 3D bioprinted constructs should emulate the anatomical features of the native tissue’s extracellular matrix (ECM). However, current bioprinting technologies can neither mimic the nano- and microscale fibrillar ECM, nor replicate the anisotropic and spatially organized architecture and gradients of complex tissues, such as cartilage, cornea, and the heart. Within BioArchitecture, we aim to develop a novel 3D bioprinter platform, capable of bioprinting hierarchical and organized biomaterial constructs at high resolution to instruct and guide cell growth and tissue maturation. The BioArchitecture platform will allow researchers and pharmaceutical companies to perform better drugs target identification in native-like bioprinted human tissues ex vivo, which will better predict the efficacy and safety of the tested drugs and significantly decrease healthcare costs by reducing the required amount of personnel, infrastructure, an animal experiments associated to a new drug development.

The neocortex is a fascinating brain structure, as it is the seat of mammalian, and notably primate, higher cognitive abilities. In the primate lineage, different neocortex morphology, in form of size and folding differences, has evolved. The development of the neocortex, and particularly of the different neocortex morphology, depends primarily on the precise regulation of the activity and behavior of cortical neural stem and progenitor cells (cNPCs), a regulation that is primarily mediated by transcription factors. One of the largest transcription factor families is the C2H2 zinc finger transcription factors (C2H2-ZFTFs), which also significantly expanded during primate evolution. Previous studies suggest that these transcription factors could be important regulators of primate neocortex development and evolution. Here, I propose that differential expression of these C2H2-ZFTFs is one essential cause of the differences in neocortex morphology between different primate species. To address this hypothesis, I plan to first identify expression differences of C2H2-ZFTFs in cNPCs of different primate species by transcriptome analysis of fetal human, macaque, and marmoset neocortex. These differences will then be tested for a functional role in cNPCs using electroporation and stable genetic modification of brain organoids. Finally, for C2H2-ZFTFs with a functional role in cNPCs, the downstream gene regulatory network will be uncovered by identification of the indirect and direct targets using RNAseq and ChIP-exo of in vitro differentiated neural progenitor cells. This will lead to a better understanding of the role of C2H2-ZFTFs in the regulation of cNPCs, while also identifying their contribution to primate neocortex development and evolution that has led to different primate neocortex morphology. This is also likely to provide novel insights into the formation of cortical malformations (e.g., microcephaly or lissencephaly).

Rapid care tests and patient-oriented bedsite testing, termed as point of care (POC) testing, have proven unanticipated relevance for the fast detection and containment of the pathogen in the course of the corona pandemic. We have developed RNA aptamer based sensors as a basis for a novel rapid care test. The sensor will give a florescent signal once the target molecule attaches to its aptameric site. The sensor as the main component of a novel POC test will be produced by a cheap and scalable biotechnological synthesis. The unique selling points of our invention are the cheap and scalable production of the sensor molecule and the high flexibility in terms of analytes that can be covered by aptamers. To proof our concept and to demonstrate the applicability of our aptamer sensors we will choose the avian influenza virus as an use case, based on the high relevance of this disease in veterinary medicine and its perception as a high risk disease for the next human pandemic. Our test will comply with the ASSURED criteria of the WHO: affordability, sensitivity, specificity, user friendliness, rapid and robust, equipment-free and deliverable to end-users Our aim is to establish a RNA aptamer based sensor as a basis for a cheap single-use test according to the ASSURED criteria. In this action, we will establish the applicability of our highly sensitive and selective RNA based sensor. We will devolop a prototype of a POC test and test the novel sensor principle under laboratory and environmental conditions. In addition, we will analyse the market and patent situation and the stepstones to be taken for an approval by the European authorities. We will finally establish our own IPR position as a basis for the further road-to-the-market.