New ISBUC collaboration to develop cyclic peptides for acid-sensing ion channels

In May 2020, Associate Professor Joseph Rogers started his own group at the Department of Drug Design and Pharmacology at the University of Copenhagen. As he explains, ‘I came from outside, very outside. I was in a different country, in industry, so when I landed in Copenhagen, I knew only a handful of researchers here. The large number of researchers doing structural biology here made it very difficult to find out what was going on. But then, I saw a poster for the ISBUC Annual Meeting.’ Joseph went to the meeting and quickly sent an email afterwards, asking if he could join ISBUC. ‘To be honest, I didn’t even know if I could join. I do not really consider myself a structural biologist, we are not depositing things in the Protein Data Bank.’

Joseph works with cyclic peptide screening. Although he is not a structural biologist by strict definition, the kind of work he does is instrumental for linking molecular structures with functional studies and cell biology. ‘We provide ligands which will help structural biologists to better understand their proteins,’ says Joseph. ‘If a structural biologist can provide a purified protein sample, if they can help identify the molecule, improve the molecule, then we in return can help a structural biologist to get to the next level, to study what effect their structure has in the cell, in the animal. Our work is part of the I of ISBUC.’ ISBUC welcomed him with open arms and since joining, Joseph has presented at the 2022 ISBUC PI Day and the 2022 ISBUC Industry Day and these talks have resulted in several new collaborations (as well as a long list of potential collaborators queuing up to work with him).

At one of these events, Joseph and Professor Stephan Pless (ILF) met Associate Professor Henriette Autzen (BMI). Henriette is a single particle cryo-EM specialist who is particularly skilled at producing and studying mammalian membrane proteins. Joseph and Stephan, who work together at the Department of Drug Design and Pharmacology, were already discussing a potential project to find inhibitors for acid-sensing ion channels. Using his cyclic peptide screening approach, Joseph would find the ligands, and Stephan — using his deep knowledge of these ion channels - would test their functionality. But they needed someone who could produce these incredibly difficult membrane proteins in vitro and help determine their structure. Henriette was exactly the person they were looking for. ‘It was an ISBUC event that brought us together and started this whole idea,’ Stephan explains.

‘Joe and Stephan both came up to me and said we need to talk’ says Henriette. This talk has now resulted in a DFF project grant worth 6.191.628 kroner. ‘There is a perfect synergy between our three groups, to the extent that it seems meant to be. I had long thought about reaching out to both Stephan and Joe to propose a collaboration. ISBUC helped us to put things into motion. I am certain that this will be the beginning of a very fruitful collaboration for years to come’ says Henriette.

This article has been adapted from Kragelund et al. (forthcoming) Meeting Report: Realising Integration in Structural Biology­­. Structure.

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