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Transport(ers) in motion – Huub Sijben

As someone who is studying the physiological and pathological mechanisms and functions of transport proteins, it can be tempting to draw analogies to real-life means of transportation. Especially so when the conference on transport proteins that you are attending is being held at the Swiss Museum of Transport in Lucerne, Switzerland, and you are in a room filled with passionate and well-versed “transportologists” from all over the world.

I started my PhD trajectory in February 2018 on the premise that I were to work for a large European IMI consortium called RESOLUTE, which would officially kick-off some five months later. RESOLUTE was founded with one overarching goal in mind: to kick-start large-scale research on a major family of transport proteins, termed solute carriers (SLCs), to unravel their importance in physiology and unlock their potential as drug targets. As it turned out, only a handful of the 400+ known human SLC proteins had been studied extensively in the past, leaving the majority of SLCs with unknown substrate, function or potential role in disease. Within RESOLUTE – which consists of 7 industrial and 6 academic European partners – the role of Leiden University in this massive task will be to deliver a new type of assay to study these highly interesting proteins in cells in a more physiological context. Thus, it has become my quest to bring this promise to fruition.

Being part of RESOLUTE means getting to know a lot of very bright and enthusiastic researchers from all over Europe. In order to keep in touch and communicate with each other about your latest findings and the next strategic approaches, the people of RESOLUTE gather in these highly structured, well-facilitated consortium meetings. As a result of this urge to convene, I have had the privilege to travel to Vienna – most of the organizational and infrastructural activities of RESOLUTE take place here – on four separate occasions in the last 12 months. So when I found out that the next conference on transport proteins (where RESOLUTE would be represented too) in August was being organized in Austria’s neighboring country Switzerland, it felt as a nice change of scenery.

For one the Swiss are known for having a rather comprehensive and efficient transport network, which is both a necessity and an impressive feat if you consider the rugged mountainous landscape that is formed by the Alps and the Swiss Plateau. My colleague Anna and I traveled by plane to Flughafen Zürich, where we could take a direct train to the centrally located city of Lucerne, which is beautifully situated along the Vierwaldstättersee. From the Luzern Bahnhof we could take a trolleybus to our Airbnb hotel, where we reached by elevator the top floor, from which we had a decent view on the remains of the old city wall. Keeping up the Dutch spirit, we decided to rent bikes to cycle each morning to the conference location, the Swiss Museum of Transport located at the central Lake, where we used the escalators to reach the conference room. From the museum, we could return to the city center by taking an old-school ferry. To traverse the river Reuss – which debouches in the great lake – the Swiss had constructed the unique Kapelbrücke, a pedestrian bridge that is now one of the main tourist attractions in Lucerne. On the mostly rainy and thunderous Tuesday a train took us to the foot of the Stanserhorn mountain, where a funicular (google that one) moved us uphill to another station from which a large cable car would take us to the peak of the mountain. Here, we could enjoy a picturesque view of the Lucerne area while dining on a rotating platform (which was not as nauseating as you would imagine).

One could go on and draw parallels between all of these tangible human transport systems and the specialized transport proteins in humans, but doing so you quickly realize it is more complicated than that. While in the real world we can quickly identify the “cargo” of the carriage, this becomes much harder on a molecular level. Luckily, the scientific community has picked up on these challenges and in the Swiss Museum of Transport it became evident that transporter research is more present and relevant than ever: from the increasing importance of SLC transporters in cancer metabolism to currently marketed dual therapies (Orkambi) targeting CFTR in patients with cystic fibrosis. One thing is for sure: transporter research will continue to open new gates and avenues for the years to come.

After the conference, when we arrived back at Schiphol by plane, we took the train to Leiden Centraal and checked out with our OV chip card; now NS knows we have passed the gates. If only we could do something similar with transport proteins…



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