Protein-Protein Interactions (PPIs) form the foundation of many physiological processes. Single-molecule studies of PPIs have revealed a wealth of information on interaction dynamics, conformational changes, and their modulation. The work-horse technique to study single molecules is fluorescence microscopy, but the diffraction limit of light limits this approach to low (nanomolar) protein concentrations. Many protein interactions in our body occur at high micromolar concentrations, which remain extremely difficult to study with existing techniques. In our group we have developed plasmon-mediated approaches that enable the study of single-molecule interactions at high concentrations. This approach is based on plasmon-enhanced fluorescence that exploits the strong confinement of the excitation volume by a plasmonic nanoparticle, while simultaneously enhancing the fluorescence intensity.
The candidate will use plasmon-enhanced fluorescence microscopy to study PPIs at high micromolar concentrations. The project will focus on 14-3-3 protein and its interactions with multivalent binding partners. The candidate will functionalize gold particles with protein and use single-molecule microscopy to quantify the timescales and heterogeneity of multivalent PPIs. In addition the candidate will push the limits of plasmon-enhanced single-molecule sensing in terms of protein concentration and temporal resolution.
The project will be supervised by dr. P. Zijlstra and co-supervised by prof. L. Brunsveld (Chemical Biology group) at TU/e. Close collaboration is expected with a PhD student in the group of Brunsveld working on the expression and functionalization of the proteins.
We welcome applications from candidates with a MSc degree in physics or biophysics with experience in single-molecule microscopy. Affinity with nanoparticle functionalization or quantitative analysis of microscopy data is an advantage.
Do you recognize yourself in this profile and would you like to know more? Please contact
dr. P. Zijlstra, p.zijlstra[at]tue.nl.
For information about terms of employment, click here or contact HRServices.flux[at]tue.nl
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