Annette Aichem
How FAT10 influences SUMO conjugation
We have recently identified a novel function of the cytokine-inducible ubiquitin-like modifier FAT10 (HLA-F-adjacent transcript 10) in that it interferes with SUMO (small-ubiquitin-like modifier) conjugation. FAT10 expression is highly upregulated under inflammatory conditions, while SUMO was recently described to exhibit anti-inflammatory properties. In addition, FAT10 and SUMO can compete for the same modification sites in substrate proteins. The goal of our current project is to characterize this SUMO-FAT10 counterregulation in more detail on the structural as well as on the functional level. We are also interested in taking a deeper look at the outcome of FAT10 induction on the SUMOylation of specific SUMO substrates as well as on the overall SUMOylation pattern during inflammatory and cancer related processes.
Oleksandra Kukharenko
Advanced state characterization of proteins and protein complexes
General goal of the project is by combining molecular dynamics (MD) simulations and novel techniques of statistical analysis and machine learning we will address problems related to the characterization of functional conformational changes of proteins and protein complexes. MD can be an efficient and thorough tool to complement experimental methods when appropriate descriptors are chosen. Those descriptors allow not only a better characterization of MD data (clustering, kinetic modeling), but more importantly they can guide efficiently any further investigation of the system both from the theoretical (convergence questions, enhance sampling methods, coarse graining etc.) and experimental (optimize the positioning of spectroscopic (e.g. EPR) labels, propose changes in experimental conditions) points of view. For example, formally the problem of positioning of EPR labels can be seen as dimensionality reduction problem with subsequent optimization: how among all possible pair-wise distances one can optimally choose a minimal amount of label positions with which one would be able to distinguish the states of interest. The challenge in this case is that the obtained low-dimensional descriptors should have a physical interpretation (positions of labels), which is not the case for many of the widely used dimensionality reduction methods. We would need to extend the standard dimensionality reduction algorithms, and correctly correlate physical distances with obtained projections, accounting for physical and theoretical restrictions.
Karthikeyan Navalpur Annamalai
Role of chaperones in the clearance of protein aggregates
Protein folding is critical for any generic cells to function normally. Proteostasis, in assistance, with several chaperones preserves protein in its very functional conformation. Abnormally folded i.e., misfolded protein molecules are either repaired by chaperones or actively degraded and eliminated by cellular proteasome pathways. In this project we will investigate how chaperones and co-chaperones aid living cells to eliminate the toxic protein substances.