Stress is the foremost consequence of human life and became a pressing societal burden through the many sensory and societal pressures that have evolved during the past decades. Severe stress induces maladaptive changes in the brain that clinically manifest as post-traumatic stress disorder (PTSD). Despite ~4% of the population presenting PTSD, only symptomatic therapies are available. In the ’SECRET-CELLS’ ERC award, we have identified a multimodal neurocircuit that induces brain-wide sensitization to stress through the sequential recruitment of hypothalamic, midbrain and then cortical neuronal circuits. Particularly, we identified protein targets that can simultaneously affect hormone and neurotransmitter release within this circuit and whose knock-out makes mice stress resilient. Therefore, we used unbiased proteomics to select protein interactors that participate in the related signaling cascades, determined the biochemical parameters of any such interaction and the X-ray structures of the relevant protein complexes. Moreso, a high-throughput screen was established to identify inhibitors. Here, we will apply this knowledge to use interacting proteins as templates for small-molecule inhibitor discovery and hit optimization. Subsequently, we will profile the pharmacology and cytotoxicity of the candidates in vitro. Thus, we will take critical steps towards developing a ‘circuit breaker’ that can inactivate the neuronal contingents that are causal to the development of PTSD. Thereby, we will offer a fundamentally novel framework for pharmacotherapy.

Understanding how the coordinated activity of neurons in multiple brain regions achieves robust behaviour is one of the most fundamental questions in neuroscience. Although recent single-cell technologies enable addressing this question by recording from large neural populations, they are limited to surveying focal brain regions and superficial cortical layers. Without an analytical framework to jointly model isolated measurements, we cannot hope to understand and quantitatively model how single-neuron dynamics give rise to distributed computations. I hypothesise that global brain dynamics fall on distinct attractor states during a given stimulus or task. Attractors naturally give rise to invariant representations, dynamical motifs independent of the sampled neurons’ identity. Inferring these invariances would allow reconstructing activity in extended regions from incomplete local recordings to reveal brain-wide cognitive processes. Further, composing invariances would provide insights into the neural correlates of generalisation, with a broad impact on neuroscience and machine learning. I propose a novel mathematical theory combining abstract combinatorial dynamical systems theory and modern machine learning to infer and compose invariant latent dynamics across measurements. We will use this theory to unify large-scale cell-resolution recordings of the mouse and macaque cortex into a common model to make cell-specific predictions across several brain regions. Our results could fundamentally challenge our view on distributed cognitive computations by revealing moment-by-moment single-neuron dynamics in spatially distributed neurons. Further, my theory will help understand how the brain generalises knowledge across tasks by composing and repurposing invariances. More broadly, my theory will open new avenues for machine learning and neuroscience to interact through sharing and shaping the dynamical processes that underpin neural computations in vivo and in silico.

Skin diseases affect 900 million people worldwide. Despite major efforts gaining insights in the disease mechanisms underlying Atopic Dermatitis (AD), the most common inflammatory skin disease (ISD), an effective treatment is currently lacking. AD is accompanied by skin and gut microbiota dysbiosis, suggesting an uncharacterized interplay between skin and gut. Furthermore, antimicrobial peptides (AMPs) that limit growth of bacteria in the host, were found deregulated in ISDs and Inflammatory Bowel Disease. Most of the host-microbe interactions are mediated by microbial metabolites that can spread and affect distant organs. INTERACT will investigate how skin microbial metabolites influence skin and gut inflammation through innovative research at two world leading research Universities, the Medical University of Vienna, Austria and University of California San Diego, USA under the supervision of Profs. Erwin Wagner and Richard Gallo, respectively. Recent results from the applicant demonstrated gut alterations with neutrophilic infiltration and increased fecal AMPs in a genetically engineered mouse model (GEMM) of AD generated in E. Wagner’s laboratory. Hence, this study will test the hypothesis that skin-derived microbial metabolites promote skin-gut inflammation inducing AMP expression and neutrophil recruitment. Using state of the art technologies, such as metabolomics and novel GEMMs, as well as patient-derived material, this project will determine the therapeutic and biomarker potential of microbial metabolites, which will have profound implications for ISD. The experimental approach combines the applicant’s expertise in host-microbe interactions with E. Wagner´s competence in mouse genetics and inflammatory diseases, as well as R. Gallo´s knowledge of AMPs and skin microbiome. The MSCA PF will support the applicant´s career development by fostering acquisition of mechanistic and complementary skills, while studying a global health problem and economic challenge.

One of the top priorities of the Medical University of Vienna is internalisation, which is a guiding principle throughout teaching and research. The mobility activities provide for a development of international contacts and networks through partnerships on all levels, an increasement of possibilities for mobility for students and researchers and other staff. The International Office for Student and Staff Affairs provides support for students and staff for the organisation and realisation of European and international mobility activities via several means of communication: personal counselling during office hours, via email and phone and through the website: www.meduniwien.ac.at/internationalmobility.The IO services the following activities: Student mobility for studies Student mobility for traineeshipsStaff mobility for teaching Staff mobility for trainingIt is guaranteed that the mobility of students and staff for the purpose of general and vocational education relies on a learning agreement/training agreement for students and on a mobility agreement for staff. These agreements are closed between the home institution and the hosting institution (enterprise) and the participants of the mobility ahead of the mobility.In total 145 interinstitutional agreements have been closed. In this context the following mobilities were carried out:Student mobility for studies (outbound) 148Student mobility for traineeships (outbound) 105Staff mobility for teaching (outbound) 4Staff mobility for training (outbound) 1Student mobility for studies (inbound) 113Student mobility for training (inbound) 58If required the IO supports incoming and outgoing mobility participants in obtaining visa. The IO also provides support for the conclusion of insurances for incoming and outgoing mobility participants. Incoming and outgoing participants enjoy academic equal academic treatment and the same scientific services. Incoming mobile participants are integrated in the daily routine of the institution. All achievements mentioned in the learning agreement belonging to the participant’s degree are accredited if they have been successfully completed by the mobile students. All incoming mobile participants and their home institutions are provided with a transcript of records including a detailed, prompt and complete list of all academic achievements at the end of the mobility.The reintegration of mobility participants receives support and at their return the participants are enabled to make use of their experiences for the benefit of the institution and their colleagues/co-students. It is also guaranteed that the staff receives accreditation for their teaching/educational activities based on their closed teaching/learning programme. Ahead of the mobility students have to apply for a statement of recognition in advance in the International Office for Student and Staff Affairs for submission to the organ in charge of recognition.After the mobility the student has to hand in his/her transcript of records as well as other evaluation documents in the International Office for Student and Staff Affairs. After examination of the documents and in case of equivalence the organ in charge of recognition signs the statement of recognition. Based on this statement of recognition the academic achievents are transferred into the student’s record at the home institution. The possibility of mobility for university staff is communicated on the website of the Medical University of Vienna and at in-house events hosted by the Human Resources Development Department. The International Office for Student and Staff Affairs provides administrative support regarding the required key documents. The application has to be entered into an internet-based application. The amount which the European Union has allocated to the Medical University of Vienna for staff mobility within the scope of ERASMUS is increased by the Medical University of Vienna by additional financial means from the global budget. Staff mobility is supported by: continued payment during the time abroad as well as a financial grant depending on the length of the mobility.

Impairments in self-regulation of emotions are a substantial aspect of neuropsychiatric disorders such as anxiety disorder, major depression, bipolar disorder, and borderline personality disorder. These disorders account for up to 40% of years lived with disability, with depression as the main cause. Key characteristics of these disorders are changes in emotion processing, i.e. emotion perception, emotion reactivity and emotion regulation. From a brain network perspective, these emotion processing alterations were found to be associated with reduced activity in the prefrontal cortex (dorsolateral and ventrolateral prefrontal cortex), while at the same time limbic areas (particularly the amygdala) are overactivated. Transcranial magnetic stimulation (TMS), a non-invasive technique for modulating brain networks, is a promising tool to cure patients suffering from affective disorders. Current approaches, however, use TMS targets based on generic anatomy coordinates from group-average studies. It is this lack of patient-specific targeting which most probably causes the modest response rates observed in TMS therapy. This project will use cutting-edge neuroscience methods to provide innovative ways for the treatment of patients with emotional dysregulation. We will systematically investigate different network properties underlying emotion perception, reactivity and regulation in healthy participants to develop a connectivity-informed process model of emotion processing that could be used for clinical research. We will use individualised brain targets based on activation and connectivity patterns obtained in the same subject to improve TMS application accuracy and achieve optimal therapeutic benefit in each and every patient. We will compare the performance of this precision-medicine approach with subject-specific stimulation targets to the current gold-standard procedure relying on group-average targets.