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Kistemaker obtains PhD cum laude on production of ground-breaking molecules

A month ago it was Marc Baggelaar, and now Hans Kistemaker too has obtained his PhD cum laude at the Leiden Institute for Chemistry (LIC). ‘He has made ground-breaking contributions to the world of protein modification,’ says PhD supervisor Gijs van der Marel. Kistemaker obtained his PhD on 11 May 2017.

Is it highly likely that for you adenosine diphosphate-ribosylation does not ring a bell, but the scientific world does not understand this process well either. Kistemaker’s research provides other researchers with the tools to change this.

Understanding by copying

ADPr plays an important role in different processes in the body, including the repair of DNA damage. In addition, scientists have shown that it is involved in several diseases, such as specific types of cancer. ADPr is a process that attaches one or multiple ADP-ribose groups to a protein, causing the protein for example to be deactivated. ‘Making these naturally abundant ADP-ribose molecules in the lab could contribute to research on the influence of ADPr on different processes in the body,’ says Kistemaker about the value of his research.

New methods

In order to make these molecules, Kistemaker developed multiple new methods. ‘Ultimately, I synthesised multiple peptides with a ADPr molecule attached.’ A peptide is a molecule which consists of a small number of amino acids that can serve as building blocks for a protein. ‘These peptides have been used in various biological experiments as part of international collaborations,’ Kistemaker says. ‘Besides the fact that these molecules give more insight into ADPr, the new synthesis methods from this research are also applicable to the synthesis of other molecules.’  

More complicated than DNA

'Making nucleic acids, such as DNA and RNA, in the lab has been essential for molecular biology. For instance for the clarification of the human genome,’ says van der Marel. ‘ADPr-molecules can be seen as an even more complicated form of nucleic acids. It is almost impossible to isolate ADPr proteins from nature. Hans Kistemaker's research provides the first steps towards clarification of the ADPr process,’ says Kistemaker’s PhD supervisor Van der Marel. This explains why many scientists are interested in these molecules. ‘Hans is co-author of publications with top scientists at the Johns Hopkins School of Medicine, the Ludwig-Maximilian University of Munich and the University of Zurich.’

Extremely difficult chemistry

‘Around ten years ago, we started making ADP-ribosylated biomolecules here in Leiden,’ says co-supervisor Dima Filippov. ‘This chemistry is so difficult that only a small number of groups in the world dare to explore it. More than synthesising very simple model molecules has not been done before. Due to results that Hans has obtained, various ADPr molecules are now accessible for researchers around the world. These molecules can be used for biological research on the structure and function of ADPr.’    

Versatile and innovative

‘What I liked about this project is that I needed many different types of chemistry to obtain the intended molecules,’ says Kistemaker. ‘I learned about a wide range of new things, such as sugar chemistry, peptide chemistry – connecting amino acids to form small proteins – and nucleic acid chemistry – involving molecules strongly resembling DNA and RNA.’ What does he think earned his PhD a distinction? ‘Obtaining my PhD cum laude is above all an honour, but it is also a recognition for my contribution to science and ADPr research in particular. The versatility and the innovative character of my thesis most likely played a role in this,’ Kistemaker concludes.