Thesis projects

We offer various possibilities for doing a thesis or internship on the topics that our PhD students work on. You can find these on our Research page. If you are interested in one of the topics, feel free to contact the responsible PhD student directly.

In addition, we also offer projects on the topics described below.

Additional thesis projects

Design of artificial collagen proteins

Collagen is the most abundant protein in mammals and makes up about 30% of our body weight. Not so much of a surprise therefore that molecular errors in collagen are implicated in many diseases, and that collagen is also a key biomaterial, for example as a matrix for growing cells in regenerative medicine. Collagen is also the prime natural example of hierarchical assembly in biology: from polypeptides to triple helices, fibrils and fibers.

We want to understand how this hierarchical self-assembly is encoded in the primary sequence of collagen proteins. Ideally, we would like to understand it so well that we can design our own collagen molecules that should self-assemble in a way designed by us. We work along two lines: computer simulations on simplified models of collagen triple helices, and protein engineering to design simple self- assembling collagens, based on sequences for primitive bacterial collagens that by themselves do not yet self-assemble.

Techniques (experimental): in-silico DNA design, molecular cloning, protein expression in E. coli, protein purification & characterisation (SDS-PAGE, mass spectrometry), protein spectroscopy (circular dichroism, differential scanning calorimetry, electron microscopy, atomic force microscopy)

Techniques (theoretical): Langevin dynamics computer simulations, molecular dynamics computer simulations, Python programming

Contact
Renko de Vries – renko.devries@wur.nl

A simple collagen-like peptide that forms the characteristic triple helix. To improve the stability it is fused to a trimerization domain.
Coarse-grained simulations of collagen fibrils, where the beads represent amino acid triplets (charged, hydrophobic or hydrophilic).
Natural collagen fibers that show the well-known banded pattern,
visualized with electron microscopy.

Directed evolution of protein materials

Natural proteins continuously evolve in a direction that optimizes the fitness of the organism. “Evolution-in-a-test-tube” (also known as directed evolution) is highly successful for improving enzymes and for finding proteins that bind to selected targets. But can we also use directed evolution to make new protein materials? So far, this is an outstanding challenge because nobody knows how to do screening of material properties for proteins produced by a library of bacteria. The problem is that you need to screen the protein material properties at the single cell level.

In order to work towards directed evolution of protein materials, we can start with an example for which we might be able to screen material properties at the single cell level. One such example is the so-called structural amyloids of bacteria: these are proteins that assemble into beta-sheet rich fibrils on the outside of bacteria, and which are part of the “biofilm-forming” substances produced by many bacteria.

Contact
Renko de Vries – renko.devries@wur.nl

The project will be done together with Johannes Hohlbein at Biophysics (BIP), who will provide access to TIRF-based super-resolution microscope allowing to get very detailed fluorescent images of the growing fibrils.

Techniques: basic molecular biology (handling E. coli cells), bio-conjugating fluorescent moieties to CsgA fibrils, TIRF microscopy, super-resolution microscopy.