The Molecular Plasmonics group at Eindhoven University of Technology has an open position (4-year PhD) wherein the candidate will develop plasmonic nanosensors to study single-molecule protein interactions across a broad range of timescales. In collaboration with a PhD candidate at the Chemical Biology group the nanosensors will be used to study the effect of drugs on multi-valent interactions of proteins that are involved in neurological disorders.

Background

The current work-horse technique to study single molecules and their interactions is fluorescence microscopy. However, the diffraction limit of light results in a relatively large probe volume that limits this approach to low (nanomolar) protein concentrations. Many protein interactions in our body occur at micromolar concentrations, which remain extremely difficult to study with existing techniques. Our group has developed a single-molecule protein sensor based on plasmon-enhanced fluorescence. By exploiting localized plasmons this sensor enhances the emission intensity of a single molecule up to 1000-fold while simultaneously shrinking the probe volume >104 times. This opens the window to studying single-molecule interactions at high concentrations and on a broad range of timescales.

Project description

You will use plasmon-enhanced fluorescence microscopy to study protein interactions at the single-molecule level. You will push the limits of the sensor in terms of the accessible concentrations (toward high micromolar concentrations) and timescales (from microseconds to hours). You will then characterize the interactions of multivalent proteins (e.g. 14-3-3 protein) that are involved in neurological disorders. Quantification of the kinetics and their heterogeneity at the single-molecule level will enable us to study how drug molecules modulate the interaction kinetics. The project will not only provide a new single-molecule platform to study multi-valent interactions, but will also reveal the mechanism by which small-molecule drugs modulate protein interactions.

The project will be supervised by dr. P. Zijlstra (Molecular Plasmonics group) and co-supervised by Prof. L. Brunsveld (Chemical Biology group) at TU/e. You will closely collaborate with a PhD student in the group of Brunsveld working on the same project but with a focus on the synthesis and functionalization of the proteins.

We welcome applications from candidates with a MSc degree in physics or biophysics with experience in microscopy. Affinity with nanoparticle functionalization or quantitative analysis of microscopy data is an advantage.

• A meaningful job in a dynamic and ambitious university with the possibility to present your work at international conferences.
• A full-time employment for four years, with an intermediate evaluation (go/no-go) after nine months.
• To develop your teaching skills, you will spend 10% of your employment on teaching tasks.
• To support you during your PhD and to prepare you for the rest of your career, you will make a Training and Supervision plan and you will have free access to a personal development program for PhD students. At TU/e we challenge you to take charge of your own learning process.
• A gross monthly salary and benefits (such as a pension scheme, pregnancy and maternity leave, partially paid parental leave) in accordance with the Collective Labor Agreement for Dutch Universities.
• Additionally, an annual holiday allowance of 8% of the yearly salary, plus a year-end allowance of 8.3% of the annual salary.
• Should you come from abroad and comply with certain conditions, you can make use of the so-called '30% facility', which permits you not to pay tax on 30% of your salary.
• A broad package of fringe benefits, including an excellent technical infrastructure, moving expenses, and savings schemes.
• Family-friendly initiatives are in place, such as an international spouse program, and excellent on-campus children day care and sports facilities.