Collaboration in person

Who did you collaborate with last year? This is a question that Oncode Investigators are asked every year. Anastassis Perrakis came up with a particularly impressive list of collaborators in 2020. His group at the Netherlands Cancer Institute specializes in structural biology. They are investigating the structure of proteins involved in cell division and those involved in lysolipid signalling.

Anastassis Perrakis

Oncode Investigator - the Netherlands Cancer Institute

Moving beyond competition: collaboration as a starting point

Why is your list of collaborators so long?

“My research group is using and developing advanced technologies to study biological molecules. This type of work calls for expertise from multiple fields, including physics, chemistry, data science and biology – a blend of expertise that is often useful for others who are seeking to answer specific biological questions. Our Proteins4Oncode facility also acts as a catalyst for collaborations, and the GPU facility leads to different interactions; we set this GPU facility up in collaboration with Lodewyk Wessels (NKI), Lude Franke (UMCG), and Jeroen de Ridder (UMC Utrecht) to facilitate artificial intelligence and machine learning projects. Another reason I collaborate a lot is that I enjoy addressing many different biological problems from the perspective of molecular structure and mechanism. I collaborate with others so that we can jointly answer the most interesting and relevant research questions.”

"My research is strongly collaborative, teaming up with various investigators to answer exciting questions through structure-function studies. It is difficult to perform this type of research in the current science funding system, with grants earmarked for specific projects. Serious joggling is often needed to team up with investigators from different disciplines.”

Can you give an example of an exciting research question?

“One of my main research lines focuses on lysolipid signaling. This started in 2003, when my colleague at the NKI – Wouter Moolenaar – was studying lysophosphatidic acid (LPA). This is nature’s simplest phospholipid. It acts as a growth factor and is involved in many biological processes, including cell proliferation and migration. Wouter was wondering how this simple phospholipid could be involved in so many processes and if it could play a role in metastasis.”

“First we collaborated with Pfizer to reveal the structure and function of the LPA-producing enzyme autotaxin. Then, we went on to create inhibitors for this enzyme in collaboration with chemists. We gradually discovered that the biochemical mechanisms of action of autotaxin were far more complicated than we originally assumed. For instance, we found out that the enzyme itself has a signaling function, not only the product of the enzyme. That in turn resulted in a collaboration with the company Galapagos, in which we are trying to understand how this works. More recently, we have set up a collaboration with OI Leila Akkari (NKI) to find out if autotaxin could play a role in liver cancer.”

“We are currently also collaborating with Oncode Investigators Jannie Borst and Ton Schumacher to explore the potential effect of autotaxin on the success of immunotherapy. All together, also with Wouter Moolenaar and others, we recently discovered that autotaxin acts as a chemorepellent for T cells. We suspect that autotaxin prevents immune cells from infiltrating a tumour, which is a big problem in immunotherapy. So, we are exploring the options to inhibit this enzyme in cancer patients that receive immunotherapy. This is an unexpected but promising collaboration of experts in biochemical signaling, immunology, mouse models and structural biology. Taken together, I think that our lysolipid signaling work is a nice example of how we started small and a little old-fashioned by investigating the structure of an enzyme, and ended up with a mature research line with a large network of academic and industrial collaborators.”

What did you learn from your collaborations with industry?

“I have worked with multiple large pharmaceutical companies. They are very reliable in my experience; they are always true to their word. These companies employ outstanding scientists that have amazingly deep insights into specific biological mechanisms. These scientists appreciate being exposed to the ‘free science’ in academic research groups and they enjoy collaborating on challenging research questions. I have to admit that my experiences with smaller companies have been mixed. They are often under pressure because they work on short funding cycles, which may dampen the spirit of collaboration sometimes. However, other small companies are exciting hubs of creativity and scientific innovation.”

In your opinion, does the current science system encourage collaboration?

“Collaboration is a buzzword in science nowadays. But to be honest, I usually find this a lot of hot air. The majority of funding agencies, but also our peers, still evaluate research results in terms of ‘last author’ publications in high-impact journals. Oncode Institute may be an exception to this rule, because the value of collaboration is implicit in the Oncode system. It is one of the performance indicators. For instance, we are asked who we collaborated with or started to collaborate with in the annual report that we need to file. Oncode puts a lot of effort into creating opportunities for investigators to meet and talk. And importantly, Oncode implicitly provides the funding to pursue ideas that arise during such meetings. The funding that Oncode Investigators receive is not earmarked for specific projects, allowing us to spontaneously pursue bold ideas in multidisciplinary teams. I think this is unique.”


Outsmarting cancer

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Outsmarting cancer

impacting lives