Cluster of Excellence, University of Freiburg

CIBSS Cross-Sectional Topics

CST Mito-Hub – Mitochondria as Integrative Signalling Hubs:

Recent research has revealed that mitochondria and their metabolic functions are tightly connected to cellular signalling and epigenetic regulation. Accordingly, an integrative approach addressing the different scales, at which the underlying signalling processes occur, is key to advance our understanding. CIBSS-A1 analyses how the dynamic states of multi-protein assemblies control and coordinate protein biogenesis and mitochondrial function with cellular signalling. Such research will profit from CIBSS-C1 providing approaches to modulate and interrogate dynamics and specificity of signalling. How mitochondrial and nuclear gene expression programmes are coordinated, including the role of proteins that are targeted to both organelles is investigated in CIBSS-A1 and A2. Complementarily, CIBSS-B1 provides unique insight on how mitochondrial signalling is mutually coordinated with metabolism.

 

CST Signalling in Organogenesis:

Understanding the mechanisms that control the development of an organ is a paramount challenge for integrative biological signalling research. CIBSS-B2 focuses on the steps of organ development - from stem cell niche organisation through patterning of epithelial sheets to assembly of the entire organ. CIBSS deciphers how these complex cell assemblies emerge from signal integration and epigenetic reprogramming (CIBSS-A2). As an important direction, CIBSS explores mechanisms by which cellular and tissue metabolic states are sensed and coupled to growth, organisation and function during development and regeneration. Precise synthetic tools for spatial patterning are applied (CIBSS-C1) to interrogate how dynamic molecular signals are propagated and integrated into multicellular patterning.

 

CST Signalling Roots:

CIBSS applies its integrative approach to the study of signalling processes emanating from plant roots in order to dissect the molecular basis of agronomically beneficial traits. CIBSS focuses on the mechanisms by which plants sense external signals such as water and nutrient availability or the presence of symbiotic bacteria in the soil. CIBSS sheds light on the molecular basis of signal perception and propagation (CIBSS-A1) as well as how these signals modulate epigenetic programming (CIBSS-A2) to control plant growth and adaptation to varying environmental conditions (CIBSS-B2). Such integrative understanding provides the mechanistic basis for transferring beneficial signalling mechanisms to agronomically important plants (CIBSS-C2), with the aim to engineer signalling modules in crops to enhanced resilience and reduced dependence on industrial fertilisers.

 

CST Integrative Immune Signalling:

Through integrative research, CIBSS yields a comprehensive understanding of how the dynamic molecular processes occurring at the activating and inhibitory receptors of T cells are perceived and propagated, integrated with metabolic cues and finally translated into acute and long-lasting immune responses. CIBSS translates this integrative insight into strategies addressing important bottlenecks that currently limit efficacy of T cell-based therapies for example, against cancer. In a comprehensive approach, CIBSS (i) engineers the T cell receptor nanocluster to specifically unleash its full signalling capacity (CIBSS-A1, C2), (ii) targets, re-positions and thus attenuates inhibitory receptors to reduce tumour- mediated T cell inhibition (CIBSS-A1, -C1, -C2), and (iii) develops strategies to optimally align T cell metabolism with anti-tumour activity to reduce T cell exhaustion (CIBSS-B1, C2).