SyNergy research projects are organized into 3 Research Areas (see Figure), each targeted at one specific pathomechanistic “nexus”. These Research Areas will be complemented by a Core Expertise, which bundles systems neurology-specific expertise to make it accessible to all SyNergy projects. The Research Areas comprise up to three “Nexus Complexes” of projects, which are directed at related problems and bring together scientists with complementary pathomechanistic and core expertise.
SyNergy will accomplish this for example by so-called "Tandem Projects": These are highly collaborative research projects aimed at improving our understanding of degenerative, inflammatory and glio-vascular disease. The projects combine expertise across traditional pathomechanisms, as well as systems biology and systems neuroscience tools. Furthermore, in many projects research efforts of basic scientists and clinicians are bundled. This allows us to combine approaches that range from in vitro models to investigator initiated trials.
Research Area A – Inflammatory mechanisms of neurodegeneration
Shared cellular programs of neuroinflammation and neurodegeneration: We plan to perform a comprehensive analysis of shared cell biological mechanisms of axon and synapse injury in degenerative and inflammatory conditions.
Determinants of inflammatory neurodegeneration: We will identify molecular master regulators that act as brakes or accelerators of immune-mediated neural damage in MS.
Compensatory plasticity after neuroinflammatory and neurodegenerative injury: We will investigate the compensatory response to inflammatory and degenerative damage at the neuronal network level.
Research Area B – Bi-directional relationships between vascular dysfunction and neurodegeneration
Targeting the interplay between vascular and neurodegenerative mechanisms in dementia: We will explore the cross-talk between amyloid pathology and the neuro-vascular unit in animal models, but also a clinical study. In parallel, we will use a novel proteomics approach to obtain an unbiased spectrum of proteins shed by Aβ-generating proteases that need to be considered when modulating amyloid production.
Vascular dysfunction in ALS and FTLD: This Nexus Complex is dedicated to testing the novel hypothesis that the functions of several proteins that are mutated in ALS/FTLD-U converge on neuro-vascular dysfunction.
Research Area C – Glio-vascular response to inflammation
Bi-directional communication between the immune and vascular compartment: Here we will determine how bi-directional interactions between T cells and glio-vascular components regulate immune cell entry into the CNS.
Systems biology of reactive glia in neuro-vascular, degenerative and inflammatory conditions: We will perform a comprehensive analysis of the phenotypic spectrum of activated microglia and reactive astrocytes in inflammatory, ischemic and degenerative conditions of the nervous system.