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ReelinSys - Systems biology of Reelin-associated neuropsychiatric disorders

Systems-level analysis by mathematical modelling of Reelin signalling as a paradigm to identify new pharmacological targets for the treatment of neuropsychiatric disorders.

The main goal is to establish an integrative dynamic mechanistic model of the Reelin network

  • to predict the behaviour of the Reelin signalling network
  • to understand Reelin-associated neuropsychiatric disorders

The integrative dynamic mechanistic Reelin network will enable

  • the identification of novel neuropsychiatric drug targets
  • the definition of desired biological effects or toxicity pathways of currently used and potential novel neuropsychiatric drugs

Psychiatric disorders are among the most prevalent causes of disability worldwide. Despite their major importance, the neurobiological origin of virtually all psychiatric diseases is unknown. Classical approaches to analyse psychiatric diseases have focussed on individual signalling targets. Most causal hypotheses have been derived from the receptor targets of psychopharmacological drugs, which are capable of bringing to remission and preventing relapses of many disorders. However, true innovations in psychopharmacology have been sparse in the last decades and psychiatry is far from delivering causal cures for most of its chronic disorders. Despite the well-established high heritability of most psychiatric disorders, even large-scale genetic studies have so far failed to substantiate plausible genetic origins. Therefore, it seems highly unlikely that the most important psychiatric disorders are caused by single genetic mutations, which could be detected by traditional genetic methods. Given this background, the use of innovative methods in pathophysiological and psychopharmacological research in psychiatry is urgently needed.

Alterations in the Reelin signalling pathway can be detected in many different psychiatric disorders and DNA variations in Reelin signalling molecules are known. Despite the current deep level of knowledge on the role of Reelin during development, its role in the complexity of psychiatric disorders is not entirely clear. Therefore we will use the Reelin signalling pathway as a window to understand more about the origin of mental diseases.

Here a quantitative systems biology approach is promising as it combines the understanding of complex and dynamic signal transduction pathways, like the Reelin signalling pathway, with a hypothesis-driven search for genetic defects. Systems biology is specifically suited to elucidate dynamic gene-environment interactions that have been predicted to be involved in the pathomechanism of many psychiatric diseases. By implementing quantitative systems biology approaches, we hope to understand how Reelin exerts its diverse biological functions.

The simultaneous generation and integration of genomic, transcriptomic, proteomic and signalling data related to Reelin should allow the construction of mathematical networks that provide a novel framework for understanding the molecular basis of psychiatric disorders which are linked to this outstanding signalling molecule.


  • AG Leemhuis (Coordination)
  • Herz/Bock (Co-Coordination)
  • AG Timmer, Physik (Co-Coordination)
  • AG Roth (IMTEK)
  • AG Schlosser (ZBSA)
  • AG Normann (Psychiatry)
  • AG Michoel (FRIAS)
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