3 Postdoc Positions in Cross-seeding of Protein Aggregation at VIB Switch Laboratory, K.U.Leuven, Norway: VIB is a life sciences research institute, based in Flanders, Belgium. We perform basic research with a strong focus on translatin​g scientific results into pharmaceutical, agricultural and industrial applications.

The VIB Switch Laboratory, K.U.Leuven is focused on understanding the mechanisms gearing protein folding and misfolding and their relation to human disease. In particular we are investigating how protein aggregation affects the interactome by suppressing native interactions but also by introducing novel aggregation-specific interactions. The latter are especially relevant as they are are usually associated to gain of function activities such as neurotoxicity (neurodegeneration) or cell proliferation (cancer).

In the context of an ERC funded project, The Switch Laboratory wants to investigate the determinants of cross-seeding of protein aggregation and their role in human disease. The lab is looking for three post-doctoral researchers.

 

Project Background: Amyloid-like protein aggregation is a process of protein assembly via the formation of intermolecular structures by short aggregation prone sequence regions. This occurs as an unwanted side-reaction of impaired protein folding in disease, but also for the construction of natural nanomaterials. Aggregates appear to be strongly enriched in particular proteins, suggesting that the assembly process itself is specific, but the cross-seeding of the aggregation of one protein by aggregates of another protein has also been reported.

The key question that we aim to address is how the interactions of the amino acids in the aggregate spine determine the trade-off between the specificity of aggregation versus cross-seeding. To this end, we will determine the energy difference between homotypic versus heterotypic interactions and how differences in sequence translate into energy gaps. Moreover, we will analyse the sequence variations of aggregation prone stretches in natural proteomes to understand the danger of widespread co-aggregation.

 

Position 1: Biophysical characterisation of the specificity of protein aggregation

 

The candidate should have expertise in biophysical techniques and studying peptide and protein aggregation and interaction. We will employ a range of techniques, including peptide micro arrays, peptide-protein interactions using interferometry, tinctorial assays, dynamic and static light scattering, Fourier Transform Infrared Spectroscopy, Circular Dichroism and Transmission Electron Microscopy.
Position 2: Co-aggregation networks in neurodegeneration

The candidate should have expertise in (neuronal) cell culture and biochemical assays such as immunoprecipitation, filter trap, proximity ligation, toxicity assays and microscopic techniques.

Position 3: Structural bioinformatics of protein aggregation

The candidate should have expertise in homology modelling and the analysis of protein structures using 3D viewers as well as force fields, and bioinformatic programming and predictor development (ROC curves, PSSMs, HMMs,..).

We offer

The VIB Switch Lab is based at the University of Leuven (KU Leuven), Belgium. With an international reputation in the field of protein aggregation our lab provides a wealth of scientific expertise as well as extensive state-of-the-art equipment. Skills training is available, both in house and via our host institutions. For the positions described above we can offer a two year contract with a competitive salary and benefits.

Deadline: not mentioned

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