Project Details
Projekt
SFB 645: Regulation and Manipulation of Information Flow within Dynamic Protein and Lipid Environments
Subject Area
Biology
Term
from 2005 to 2016
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 5486231
Key objectives of the Collaborative Research Centre are to understand the molecular mechanisms that control the asymmetric distribution of membrane constituents (lipids, proteins), the role of lipid metabolising enzymes in membrane composition and cellular physiology, the impact of specific lipid components on membrane protein function, the role of lipid metabolites in cell signalling and the generation and application of novel tools (e.g. small molecule inhibitors) for the analysis of membrane function.
An outstanding characteristic and strength of this highly interdisciplinary research initiative is the integration of bioorganic, biophysical, combinatorial and pharmaceutical/medicinal chemistry methods for the functional analysis of membrane proteins and lipids. These include aptamers/intramer technology, small molecule inhibitors, and the application of siRNAs or siRNA-derivatives which are applied in addition to the use of classical genetic approaches such as knock out technologies in transgenic animal models (Drosophila, mice).
In Project section A, methods of synthetic organic chemistry, bioorganic chemistry, and combinatorial chemistry are applied to identify novel exogenous molecular effectors or probes which directly affect the function of integral membrane proteins or membrane-associated proteins. Identified effectors will be applied to analyse the function of target proteins in vitro and in vivo. Besides their application in functional analyses, however, they might also be of high therapeutic value. Thereby, project section A applies methods of chemical proteomics which immediately will have an effect on project section B.
The common interest of project section B, is to understand how asymmetric lipid patterns in membranes are generated and maintained and how dynamic lipid/protein interactions in the membranes determine inter- and intracellular signalling processes during development. Furthermore, the influence of lipids and cholesterol on the function of membrane proteins and the function of lipids as second messengers will be studied. Using RNAi approaches or knock out transgenic animals, key enzymes of the lipid metabolism will be blocked and the function of membrane proteins in signal transduction and cell-cell communication will be tested in these manipulated cells or animals.
An outstanding characteristic and strength of this highly interdisciplinary research initiative is the integration of bioorganic, biophysical, combinatorial and pharmaceutical/medicinal chemistry methods for the functional analysis of membrane proteins and lipids. These include aptamers/intramer technology, small molecule inhibitors, and the application of siRNAs or siRNA-derivatives which are applied in addition to the use of classical genetic approaches such as knock out technologies in transgenic animal models (Drosophila, mice).
In Project section A, methods of synthetic organic chemistry, bioorganic chemistry, and combinatorial chemistry are applied to identify novel exogenous molecular effectors or probes which directly affect the function of integral membrane proteins or membrane-associated proteins. Identified effectors will be applied to analyse the function of target proteins in vitro and in vivo. Besides their application in functional analyses, however, they might also be of high therapeutic value. Thereby, project section A applies methods of chemical proteomics which immediately will have an effect on project section B.
The common interest of project section B, is to understand how asymmetric lipid patterns in membranes are generated and maintained and how dynamic lipid/protein interactions in the membranes determine inter- and intracellular signalling processes during development. Furthermore, the influence of lipids and cholesterol on the function of membrane proteins and the function of lipids as second messengers will be studied. Using RNAi approaches or knock out transgenic animals, key enzymes of the lipid metabolism will be blocked and the function of membrane proteins in signal transduction and cell-cell communication will be tested in these manipulated cells or animals.
DFG Programme
Collaborative Research Centres
International Connection
Israel
Completed projects
- A01 - Membrane-proximal signaling events in migrating immune cells (Project Heads Kolanus, Waldemar ; Quast, Thomas )
- A02 - Kraftausübung durch adhärierende und sich fortbewegende Zellen (Project Head Merkel, Rudolf )
- A03 - Functional analysis of cytohesin-mediated membrane receptor tyrosine kinase signaling (Project Head Famulok, Michael )
- A04 - Regulation of membrane trafficking and organization by the Liprin-á protein family (Project Head Schoch McGovern, Susanne )
- A06 - Interaktion von Membrangebundenen Serinproteasen mit Enzyminhibitoren (Project Head Gütschow, Michael )
- A07 - Sphingolipid metabolism and autophagy in Alzheimer's disease (Project Head Walter, Ph.D., Jochen )
- A09 - Mechanism of non-genomic progesterone signalling in human sperm (Project Heads Kaupp, Ulrich Benjamin ; Strünker, Timo )
- A10 - Molecular mechanisms, dynamics and nano-anatomical aspects of membrane protein clustering (Project Head Lang, Thorsten )
- B01 - Role of ceramide synthases in linking cellular lipid synthesis with body fat metabolism (Project Heads Bauer, Reinhard ; Hoch, Michael )
- B02 - Cell biological characterization and function of different ceramides including sphingolipid derivatives in mice (Project Head Willecke, Klaus )
- B03 - Functions and mechanisms of endolysosomal enzymes and lipid binding proteins (LLBPs) (Project Head Sandhoff, Konrad )
- B05 - Functional consequences of altered sphingolipid metabolism in myelinating cells (Project Head Eckhardt, Matthias )
- B07 - Endocannabinoids: Metabolites of Phospholipids as Modulators of Brain to Bone Signalling (Project Heads Bab, Itai ; Zimmer, Andreas )
- B08 - Regulation of lipid synthesis in plant membranes (Project Head Dörmann, Peter )
- B09 - Physiological and pathological role of GBA2 in controlling cellular dynamics (Project Head Wachten, Dagmar )
- B10 - Physiological Function of the lipid droplet protein AUP1 (Project Head Thiele, Christoph )
- B11 - Regulation of innate immune activation by high density lipoproteins (Project Head Latz, Eicke )
- C01 - Role of mannose receptor-mediated endocytosis in antigen cross-presentation (Project Heads Burgdorf, Sven ; Kurts, Christian )
- C02 - Cell-free analysis of phagosome biogenesis in macrophages (Project Head Haas, Albert )
- C03 - Analysis of the novel multidomain protein p86DM: coordination of endocytosis, recycling and cytoskeletal organization (Project Heads Hoch, Michael ; Magin, Thomas )
- C04 - Insulin/insulin receptor transport and endocytosis in Drosophila neuroendocrine cells (Project Head Pankratz, Michael )
- C05 - Role of Wurst/Dnajc22 proteins in endocytosis at barrier tissues (Project Heads Behr, Matthias ; Hoch, Michael )
- C06 - Regulation of membrane dynamics during chaperone-assisted selective autophagy (Project Head Höhfeld, Jörg )
- Z01 - Herstellung von RNAi-Zelllinien zur funktionellen Analyse von Phosphoinositiden bei der Bildung, Transport und Regulation von Membran-Microdomänen, Lipiden und Proteinen (Project Head Schepers, Ute )
- Z02 - Central Services (Project Head Hoch, Michael )
- Z03 - Transgenic animals (Project Head Degen, Joachim )
- Z04 - Protein and lipid analysis by mass spectrometry and lipid metabolic tracing (Project Heads Dörmann, Peter ; Gieselmann, Volkmar ; Thiele, Christoph )
- Z05 - Transcriptional regulation of proteins involved in membrane biology and lipid metabolism (Project Head Schultze, Joachim L. )
- Ö - Sehen, Hören, Verstehen (Project Head Hoch, Michael )
Applicant Institution
Rheinische Friedrich-Wilhelms-Universität Bonn
Participating Institution
Max-Planck-Institut für Neurobiologie des Verhaltens - caesar (MPINB)
Participating University
The Hebrew University of Jerusalem
Spokesperson
Professor Dr. Michael Hoch
