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SFB 1557:  Functional Plasticity encoded by Cellular Membrane Networks

Subject Area Biology
Term since 2023
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 467522186
 
Life depends on the ability to adapt to changing environmental conditions. To meet this demand, organisms are equipped with sophisticated mechanisms to regulate protein function in time and space. Disentangling the mechanisms that control this functional plasticity of biological processes at the molecular and supramolecular levels is at the heart of fundamental biological research and understanding of diseases. The complex membrane networks have a fundamental function in spatially organizing metabolic pathways and many other cellular processes. There is compelling evidence that the composition and collective properties of the lipids in each organelle play critical roles in defining organelle identity and the specific functions of its proteome. Organelle-specific membrane properties governed by the lipid composition directly control membrane protein functions via intricate, highly interconnected mechanistic principles. These include (i) specific interactions with membrane lipids, (ii) the effect of bilayer thickness and lipid packing on the structural organization of membranes, and (iii) the crosstalk of proteins and lipids in determining membrane surface properties and shape. The specific regulatory functions of organellar membranes are further controlled by lateral segregation of membrane components and by membrane curvature. Moreover, membrane proteins and lipids segregate at contact sites formed between distinct organelles, or pathogens and host organelles during infection. Such spatial organization of membrane components occurs at the nanometer scale and during different stages of cell growth, or in response to stressors or nutritional changes. Our research initiative aims to address how the systems properties of membranes control the plasticity of membrane protein functions and how functionally relevant membrane properties are maintained and adapted in response to distinct environmental cues. We seek to define the mechanisms underlying such functional plasticity at membranes in various physiological and pathophysiological processes. We will follow a multiscale approach to study how functional plasticity is encoded by cellular membrane networks from the molecular and sub-cellular up to the organismic level. The consortium will develop and apply lipid tools and biomolecular mass spectrometry to map the protein and lipid landscapes at the (sub)organellar level, use light and electron microscopy to resolve the organization and dynamics of membrane networks, and structural biology approaches to elucidate membrane protein function and plasticity within their natural lipid environment. Our projects will provide insights into the physiological adaptation of membrane properties and their dysregulation in diseases caused by defects in lipid metabolism, or membrane protein assembly, targeting, or function, or by microbial infections.
DFG Programme Collaborative Research Centres

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Applicant Institution Universität Osnabrück
Participating University Universität Münster
 
 

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