Thesis subject

Bottlebrush polymers that stretch and stiffen DNA

Polymers come in many different topologies such as linear, branched, star polymer, etc. A very special polymer topology is that of the so-called “bottlebrush”, yes indeed, like the brushes you use in the lab to clean bottles and glass-ware....Bottlebrush polymers consist of a “main chain” with many grafted “side chains”. Bottlebrushes are also used in nature, for example for lubrication (in your joints, in your saliva).  An example is Aggrecan, which consist of a protein core with highly charged polysaccharide side-chains (Fig 1, left).  Aggrecan is an key molecule in cartilage, where it ensures lubrication. Due to the high density of charges the bottlebrush is able to remain swollen under high pressure.

The many side-chains around the main chain make it much harder to bend a bottlebrush than to just bend the main chain. This so-called  main chain stiffening effect is very poorly understood. We are looking for a model system in which this effect is very strong such that we can easily study it. Previously we have shown that we can use DNA as a main chain and coat the DNA with protein side-chains that have a short DNA-binding functionality (Fig. Right, you cannot see the hairs here, because the resolution is much lower than in the left image). The side-chains used for decorating the DNA were 400 amino acids long and already led to significant main chain stiffening of the DNA.

In this project we want to go one step further by chemically modifying very very long Dextran (a polysaccharide) with a few DNA-binding functionalities, such that we can get an extremely strong main chain stiffening effect, with DNA stiffnesses approaching the resolution of optical microscopes, such that we should even be able to follow the DNA contour using optical microscopy. This may have technological applications, for example in single-molecule DNA sequencing technologies.

We are looking for: a MSc/BSc student Molecular Life Sciences with a wide range of interests that include doing some synthetic chemistry, interest in biological polymers such as polysaccharides and DNA, but also an interest in physical chemistry, polymer science and nanotechnology..... 

In this project, you will get experience with:

-       Bioconjugation reactions

-       Atomic Force Microscopy and Fluorescence Microscopy of individual DNA molecules

If you are interested, please do not hesitate to contact the "contact people" given above.