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Vici grant for Jeroen Codée: ‘I want to understand how sugars are formed’

Although sugars are widely used in biological and medical research, their synthesis is still badly understood. Jeroen Codée has received a Vici grant of 1.5 million euros for systematically studying the production of sugars. ‘I want to genuinely understand the reactions.’

Sugars are everywhere

With his Vici grant, Codéé will study oligosaccharides: short chains of sugars. Sugars play a role in almost all biological processes in our bodies. Researchers are therefore keen to use them in the lab, to study such biological processes. Because most sugars cannot easily be isolated from nature, synthetic sugars are needed. However, says Codée, the synthesis of sugars is complex and badly understood. ‘Where we have been able to automate DNA for quite some time now – because the bonds are much simpler – for sugars this is not yet possible on a large scale.’

Understanding instead of using   

Codée explains the problem: ‘Every time you make a sugar bond, you can get two stereoisomers. They differ spatially, so they are different molecules. Obviously, you only want one molecule. I want to better understand the synthesis of sugars, in order to find out how to steer the reaction towards one product.’

A clear motivation, but why has no one studied this before? ‘Many synthetic chemists are goal-oriented: making a certain molecule is more important to them than understanding the reaction. But if you don’t understand the reaction, you don’t know what to do when it fails. Furthermore, detection methods and computer simulations have improved considerably, so that I can now carry out this research better.’ 

Codée explains at Eye-Openers why he wants to make sugars

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From building block to product

Codée will work in a highly systematic way using both laboratory experiments and computer simulations. ‘In the lab I will systematically vary the building blocks of the sugar chains, to study what effect that has on the formation of sugar bonds’, he says. ‘In terms of speed, but also in terms of selectivity between the two forms you can get.’

Searching for the invisible

Because Codée cannot study everything in the lab, he will also make use of simulations. In a chemical reaction, a molecule often reacts via an reactive intermediate: a product that is formed in the reaction, but that cannot be detected in the lab. ‘It is precisely these intermediates that we try to find using simulations. They provide insight into how the reaction really works'. Unique to Codées research is that he will not only perform simulations for one type of sugar, but for a whole family of sugars.

'That's quite exciting'

Inspired by nature, Codée suggested a new mechanism in his proposal: 'It is an existing mechanism how enzymes make sugars.' The mechanism can maybe better describe the exact reaction. It will be  quite exciting to find evidence for it,' says Codée. Either way, he is very happy with the grant. 'It gives your career a big boost. I can now set up a team that will fully focus on this research.' Codée plans to appoint three PhD candidates and two postdocs.

Jeroen Codée's Vici grant is not the only one for his institute, the Leiden Institute of Chemistry (LIC). Sylvestre Bonnet also received a Vici: his goal is to inhibit cancer proteins with metal-containing medicines and light. This year, 72 scientists submitted a proposal for a Vici grant in the NWO Domain Science, of which NWO awarded 12. The LIC received one sixth of the Vici grants in this domain.

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