Protein Biophysics (IMM) 

Research:

1. Protein structure and function.
2. High-resolution NMR spectroscopy.
3. Protein structure validation.

Description of research:
Working at the crossroad of chemistry, physics and biology the Protein Biophysics group studies proteins, their interactions and their dynamical behavior. We use high-resolution Nuclear Magnetic Resonance (NMR) spectroscopy and X-ray crystallography in conjunction with other biophysical techniques, such as isothermal titration calorimetry (ITC) and surface-plasmon resonance (SPR).

1. Protein structure and function
* Regulation of Ca²⁺ transport (Dr. Mark Hilge, Dr. Nadezhda Kovalevskaya, Ing. Jan Aelen, Drs. Vincent Breukels, Prof. Dr. Geerten W. Vuister)
Ca²⁺ ions are crucial in many cellular processes, including neuronal response, muscle contraction, enzyme activity, gene transcription, cell death, proliferation and differentiation. We study the regulatory mechanisms that govern Ca²⁺ fluxes across membranes from a structural- and biophysical perspective. In particular, we focus on the Na⁺/Ca²⁺-exchanger, a highly ubiquitous ion transporter that constitutes the dominant Ca²⁺ efflux mechanism in heart and sensory neurons and the TRPV5/6 Ca²⁺ channels involved in Ca²⁺ homeostasis.
* Assembly of active biomolecular complexes (Dr. Geerten W. Vuister)
Protein interaction domains play essential roles in the transport, localization, assembly and functioning of multi-protein complexes. We study the structure function relationships of the five PDZ domains of the protein tyrosine phosphatase PTP-BL and the so-called PAH domains of the transcriptional co-repressor SIN3.

2. High-resolution NMR spectroscopy (Drs. Vincent Breukels, Prof. Dr. Geerten W. Vuister)
NMR is extremely well-suited to study both the structure and fundamental properties of biomolecules, including dynamics on the time scale of pico-seconds to seconds. In this project, we develop sophisticated new NMR methodology to improve our detailed understanding of biomolecular interaction.

3. Protein structure validation (Dr. Jurgen Doreleijers, Prof. Dr. Gert Vriend (CMBI), Prof. Dr. Geerten W. Vuister)
NMR structures should adequately reflect the experimental data and be reliable in terms of overall and local quality. Our recent analysis of a large set of NMR derived structures suggested serious flaws and illustrated that the quality of NMR structures cannot be reliably evaluated using only the commonly accepted structure validation tools. In this project we develop new tools that yield better structures and new tools that help to validate data and results.

Opportunities for students:
The multidisciplinary nature of our research allows for many possibilities for your master research period. When you are interested in structure and functioning of biological macromolecules, you can work both in the lab and use the biophysical techniques (NMR, ITC, SPR) as tools in your studies (project 1, suitable for Chemistry, Molecular Life Science and Natural Science). Those with an interest in biophysics can work on the development of biophysical techniques, in particular NMR spectroscopy (project 2, suitable for Chemistry and Natural Science). Finally, those with an interest in bioinformatics approaches, programming and computers can work on the tools for structure generation and analysis (project 3, suitable for Chemistry, Molecular Life Science and Natural Science).

Specific projects will be listed on the proteins.dyndns.org website.

Mandatory bachelors courses:
Project 1 or 3: Structuur Biomoleculen or Structuur, Functie, Bioinformatica
Project 2: Magnetische Resonantie 1.
Recommended bachelors courses: Structuur Biomoleculen, Structuur, Functie, Bioinformatica, Magnetische Resonantie 1
Mandatory courses major: Determined on an individual basis depending on bachelor track (MLW, NW or Chemistry) and project.