Tekst: Lies Feron
Foto's: Saskia Vanderstichele
“That’s all there is to it,” says professor of statistical physics Dominique Maes, when she shows us the cleanroom where her PhD student has built an installation in which he examines the phase transitions of proteins. It’s a phrase that will come up again and again: Maes has the gift of explaining extremely complex processes in a very simple way. And so she introduces us to the fascinating world of mass transport, on earth and in space.
VUB’s Structural Biology department studies phase transitions in proteins. A phase transition, or the way in which proteins converge, can occur in different ways. The proteins can form a lattice, a crystal, but they can also form a heap, an aggregate. The model in between is known as fibres. In the human body, fibres and aggregates are often linked to diseases. When a certain type of protein starts to stick together, it can no longer perform its function, causing illness or even death. Diseases caused by the accumulation of proteins include Alzheimer’s and ALS, from which Stephen Hawking died.
The fact that proteins that stick together don’t function properly is well known. But it’s not known exactly why they get stuck together. That’s why we started from scratch. We want to understand the process that causes the disease before we develop any medication.
“Whether you’re a private researcher or an academic, at SAS – Space Application Services – in Brussels, you can buy Ice Cubes of 10x10x10 centimetres and for €80,000 your experiment goes into space. You just have to make sure your experiment fits into that Ice Cube. SAS cubes are included with every ESA space flight and because ESA facilitates this, it gets a few cubes for free. And so it became interesting for ESA to develop this sophisticated new technique – depolarised dynamic light scattering (DDLS) – for those Ice Cubes. With DDLS you can immediately see the difference between a crystal and an aggregate.”
Commercial flights do offer extra possibilities for space research, Maes explains. “Ultimately, it can be said that Belgium, as a country, gains a lot from space travel. Belgium contributes a relatively large amount to the ESA. But according to economic calculations, every euro comes back three times. For example, the Belgian company Qinetic is responsible for the development of the DDLS. SAS is also a Belgian company, as is BUSOC. And the VUB research is paid for by the ESA, which is a return flow of funding.”
And that’s all there is to it.
The University of Houston website has more information about the NASA space experiment VUB is participating in: http://stories.uh.edu/ISS-experiment/index.html
“The fact that proteins that stick together don’t function properly is well known. But it’s not known exactly why they get stuck together,” says Maes. “In the past, the crystallisation of proteins was used to determine their structure. The structure of proteins provides information about their action. As a physicist-mathematician, I then asked myself about the crystallisation process itself, and that’s how I came to be in this research. Proteins move in liquids, in cells, and in all sorts of places depending on the disease you’re looking at. In each environment the proteins move in a specific way: there is therefore a specific mass transport regime. During this mass transport, phase transitions take place and the environment in which it happens certainly plays a role in this.”
“Medical companies are also interested in the crystallisation process of their medication. The shape and size of crystals are important. The pills you buy from the pharmacist contain the actual drug in crystallised form. Large crystals dissolve more slowly than small crystals and are therefore often used in medicines that need to work over a longer period of time. Small crystals, on the other hand, are an advantage if a medicine has to take effect quickly. We mainly study nucleation, which is the first step in the phase transition. How do the proteins come together and how do they organise themselves? And how can we prevent the proteins from clumping together? “
Mass transport in space
When studying phase transitions, it is useful to investigate transitions in different environments – including in space. “Space is a unique environment: there is no gravity and the molecules move very slowly towards each other, without being pulled and pushed. This specific environment provides a lot of information about phase transition,” says Maes. “All kinds of effects that you have here on earth are switched off. Research in space is one more parameter in this fundamental research.” [Continue story below the picture]
So, working with NASA, VUB has sent proteins linked to ALS into space in a very concentrated form. Research into crystal formation is important for the medical industry, among other things. Maes: “A few years ago, several pharmaceutical companies stopped studying drugs for diseases such as ALS and Alzheimer’s because it was too complicated and too expensive. That’s why we started from scratch. We want to understand the process that causes the disease before we develop any medication.”
Dandruff and pregnant rats
The Nasa experiment – a collaboration with the University of Houston – contains 18 protein solutions, including five from VUB. “Space research is above all a matter of financing, and nationality plays a major role in this,” says Maes. “At NASA, you need an American principal investigator or PI for the project, and only the PI is funded. The PI of the current NASA experiment is Peter Vekilov of the University of Houston. I am co-PI. In an ESA experiment, as a European, I am PI and get the money.” Maes is PI of European space projects on phase transitions in proteins.
Funding is one point. But research in space has to do with many more things: “Sending an experiment into space is not easy,” she says. “As with most projects, it often starts with a call, where you propose a project and a jury decides. The big difference is that you can’t get started immediately after a positive decision. The first requirement is that the experiment takes as little astronaut time as possible. In principle, the experiment should be set up in such a way that the astronaut only has to start it and the rest is done automatically.
Space is a unique environment: there is no gravity and the molecules move very slowly towards each other, without being pulled and pushed. This specific environment provides a lot of information about phase transition. All kinds of effects that you have here on earth are switched off. Research in space is one more parameter in this fundamental research.
“It seems obvious but it is important: a space experiment must be small and light and it must be delivered safely in levels of containment. At the ISS space station there is no gravity. Suppose your experiment leaks, then you have no means to clean it up. Dandruff is one of the biggest problems in the ISS: it’s full of it and you can’t clean it up because it doesn’t stick to anything and of course you can’t open a window either.”
Foresight and timing are crucial too. “Timing is important if you take into account the fact that immediate intervention is not possible. If you see something happen in a space experiment, you can’t intervene immediately like you can in your laboratory on earth. As far as timing is concerned, you also have to make sure that the proteins only start to cling together under microgravity in space and not before. I know someone who would like to investigate the birth of rats in space, but the rats had already given birth before they arrived at the space station. Will the experiment still be OK if the flight is postponed and if so, for how long? These are all quite simple questions but they are essential in space research.”
Timing is everything
There are various techniques for carrying out experiments at the desired moment. The research group at VUB mainly plays with temperatures. They send the material frozen and let the astronaut defrost it, after which the experiment begins. Yet Maes says they often have to prepare and send several experiments. They also request late access for their experiments, meaning the experiment doesn’t have to be on site until five to 10 days before the launch. [Continue story below the picture]
“Intervention is possible. From Belgium, this is done via BUSOC, the Belgian User Support and Operation Centre, a special support service in Ukkel. This contact doesn’t take place directly but via pre-developed programmes, and, in the case of a NASA experiment, programmes that have already been approved by Houston. Our experiment is mainly concerned with temperature changes that researchers can record and adjust where necessary. Luckily, our fundamental research doesn’t have to take into account the return of the experiment to Earth. We are only investigating what is happening in space.”
Commercial flights as a springboard
“Another important aspect of space research is foresight,” she says. “I have been asked to do research that takes place within three years at the earliest, but I have to decide now what and how. That’s also the big disadvantage of space research: today this protein is interesting, but in three years I might prefer to test another protein.”
For the same reason, the equipment sometimes lags behind. On the other hand, new equipment is being developed specially for some experiments. This is the case with the ESA, which is developing a device that many researchers can use because they all work with the same measuring technique. Maes’s space experiment almost didn’t take place, because ESA originally considered the equipment to be developed to be too complicated and too expensive. But a commercial provider made it possible.
Maes’s space experiment almost didn’t take place, because ESA originally considered the equipment to be developed to be too complicated and too expensive. But a commercial provider made it possible.