Physical modeling of non-equilibrium processes in biological systems

Transport, Aggregation and Molecular cooperativity

Funding period 2017-2020



SFB Symposium

Tue, 01/08/2017 -
10:00 to 16:00
Campus SB, Building E2 1 (Bioinformatik), Room 001

Robert Ernst, Bianca Schrul, David Mick, Leticia Prates Roma
Host: Prof. Heiko Rieger
Saarland Universtity, Medical School, HOM

SFB Biochemistry & Biophysics Symposium

Prof. Dr. Robert Ernst: "Membranes as responsive interfaces"

Cellular membranes are complex mixtures of proteins and lipids. As a collective, these constituents shape the bulk physicochemical membrane properties such as the viscosity, the lateral pressure profile, and the lipid phase behavior. It turns out that cells have evolved sophisticated mechanisms to sense and control these physicochemical properties both at the surface of the membrane and within the hydrophobic core. In collaboration with experts in molecular dynamics simulations, we study the dynamic interactions of membrane property sensors with the membrane environment. We aim to establish how organelles maintain their identity and function during cellular stress and adaptation. The ultimate goal to understand and control membrane responsiveness.

Jun.-Prof. Dr. Bianca Schrul: "Membrane Protein Targeting and Insertion into Lipid Droplets"

Lipid droplets (LDs) are cytosolic organelles that dynamically store the majority of metabolic energy in the form of neutral lipids. In contrast to all other organelles, LDs are uniquely encapsulated by a phospholipid monolayer, which separates their hydrophobic lipid core from the aqueous cytosol. Integral LD membrane proteins adopt a unique topology, in which a hydrophobic segment is inserted into the phospholipid monolayer in a hairpin-type fashion. Interestingly, many of these hairpin-proteins are initially inserted into the endoplasmic reticulum membrane before they partition to the LD monolayer. Extensive research revealed how transmembrane-spanning proteins are inserted into phospholipid bilayers. However, next to nothing is known about how hairpin proteins integrate into phospholipid monolayers. We aim to combine in vitro reconstitution experiments with molecular dynamics simulations to decipher how hairpin proteins are integrated into different types of membranes and how they partition between them. Together with quantitative imaging techniques to define the spatio-temporal distribution of LD-destined membrane proteins in living cells, this will provide key insights into fundamental processes of LD biogenesis from an integrated biophysical and cell-biological view.

Jun.-Prof. Dr. David Mick: "Time-resolved Proximity Labeling and Proteomics of Primary Cilia During Cellular Signaling"

Primary cilia are several µm long plasma membrane protrusions that coordinate central cellular signaling pathways. By using sophisticated protein trafficking mechanisms cilia dynamically adapt their protein content in response to external signals. Yet, how this constant re-shaping of the cilia proteome impacts the cilia signaling environment is largely unknown. We are combining advanced light microscopy and APEX-based proximity labeling with state-of-the-art mass-spectrometric methods to study the proteomic changes of primary cilia in an unbiased, quantitative and time-resolved manner. Our goal is to determine protein and second messenger concentrations in cilia during signaling to establish how the ciliary compartment processes and integrates external signals to trigger cellular cues. In light of the CRC1027, we can envision several collaborative projects to study polarized protein transport during cilia formation, to model the dynamic equilibrium of the ciliary proteome, and to unravel the impact of dynamic length control of cilia on their signaling capacity.

Jun.-Prof. Dr. Leticia Prates-Roma: "Mapping redox changes in mouse models using novel imaging and histology-based approaches"

Redox reactions are at the heart of many physiological and pathological cellular processes.  However, one of the limitations to study redox changes lie in the difficulty to specifically monitor redox species inside living organisms. In the past few years, we have developed novel imaging and histological approaches using transgenic mice expressing the genetically-encoded H2O2 probe (roGFP2-ORP1) that allows us to monitor changes in a wide-range of mouse models with subcellular resolution. During diabetes onset, H2O2 have been implicated to affect pancreatic beta cell metabolism, Ca2+ dynamics and insulin exocytosis. However, the mechanisms and the source of H2O2 is not known. In our previous work, we have extensively studied how EGSH and H2O2 impact pancreatic beta cell metabolism and survival. In the context of the SFB1027, we will address, using a combination of imaging techniques, functional assays and mathematical modelling, the role of H2O2 originated from NADPH oxidases (NOX1 and NOX2) and mitochondria on insulin exocytosis in healthy, obese and diabetic mouse models.


IRTG Lab course

Thu, 03/08/2017 - 09:00
Campus HOM

Prof. Dr. Markus Bischoff
Host: Dr. Hendrik Hähl

Practical Lab course in Microbiology


  • How to identify different bacterial species?

Biochemical and modern analytical tools

  • How toxic are bacteria?

Assay to determine the bacterial potential to lyse human red blood cells

  • How sticky are bacteria?

Assay to measure the bacterial adhesion capacity to blood serum proteins

SFB Seminar

Fri, 11/08/2017 - 11:00
Campus SB, INM (Geb. D2 5), Leibniz-Saal

Prof. Kazuhiro Nagata
Host: Prof. Dr. Aranzazu del Campo
Laboratory of Molecular and Cellular Biology, Kyoto Sangyo University

Maintenance of ER homeostasis by ER redox network

Terminally misfolded secretory and membrane proteins are retro-translocated from the endoplasmic reticulum (ER) into the cytosol where they are degraded via ubiquitin-proteasome pathway, a process termed as ER-associated degradation (ERAD). We first identified a novel protein EDEM (ER-degradation enhancing a-mannosidase-like protein) and reported that EDEM recruits glycoproteins misfolded in the ER from synthetic pathways to degradation pathways in a mannose trimming-dependent manner.  We also found a novel protein ERdj5, an ER-resident disulfide reductase, as an EDEM-binding protein and identified its function playing a central role in ERAD by cleaving the disulfide bonds of the misfolded proteins that are recognized by EDEM.Recently, wefound that ERdj5 reduces the luminal disulfide bond of SERCA2b, a Ca2+-ATPase on the ER membrane, thereby activating its pump function. Notably, we found that ERdj5 activates SERCA2b at lower ER luminal [Ca2+] ([Ca2+]ER), while higher [Ca2+]ER induces ERdj5 to form oligomers that are no longer able to interact with the pump, suggesting [Ca2+]ER-dependent regulation. These results identify ERdj5 as a master regulator of ER calcium homeostasis, and thus shed light on the importance of crosstalk among redox, Ca2+ and protein homeostasis in the ER. We also found that the reductive force for RRdj5 is provided from the nascent polypeptide entering the ER via PDI/ERO1 system.  We will discuss on the molecular basis of this electron transfer pathway from nascent chains to ERdj5.