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UBC Expertise – Proteomics

Professor Albert Heck leads the Proteomics and Biomolecular Mass Spectrometry research group at Utrecht University. Albert is well known as a member of the KNAW, and was recently presented with the prestigious Spinoza prize. Prof. Heck is founder of the Netherlands Proteomics Center, serving as its Scientific Director, as well as current Scientific Director of the Utrecht Institute for Pharmaceutical Sciences. How important is bioinformatics for Albert’s research and how did he create such a successful career?
‘I want to know how life works at the molecular level. There are many molecules that play an important role in our daily lives. I have mainly focused my research on proteins, which are major constituents of our body, and the workhorses of everything that our body does.’

The fascination of working together

‘When I started my research in Utrecht, our new field has just been termed proteomics, and the methods to sequence proteins with mass spectrometry were just in their infancy. It was very hard to identify a protein; it took a full day of work. But in the years that I have been in Utrecht, the sequencing of proteins using mass spectrometry has become so efficient, sensitive and fast that we can now sequence thousands of proteins in a proteome within a few hours. In the process, my field of expertise has shifted from analytical chemistry to mass spectrometry based proteomics.’
‘What we try to do in our lab is to identify proteins in our body, and there are many, many more than the 20,000 different genes. To identify them, you have to sequence them, and being able to do that has allowed us to expand our studies from a single protein to studying a protein in the context of all the other proteins. That’s where my fascination really began.’

Heavy reliance on bioinformatics

Advances in mass spectrometry have resulted in revolutionary steps forward in the field of proteomics. Albert explains that his entire research relies heavily on a wide range of informatics and bioinformatics.
‘Bioinformatics comes into proteomics in many ways. Our typical experiments don’t stop when we have the mass spectrometry data; they’re only just beginning. Nowadays it takes a week to measure the data, and it takes another two or three months to analyse the data to the point where you can really say: now I have the biological information I’m looking for.
So we generate big data sets. Handling these datasets, stewardships and storage; that’s part of IT. But in order to study how proteins work together, we talk about network interactions; different layers of interactions that require all kinds of bioinformatics, from modelling and fitting data, to existing literature and current knowledge. So bioinformatics is a key element of conducting proteomics research.’

Integral part of Utrecht Bioinformatics Center

‘Every researcher in my group needs to be able to do some programming and must understand informatics papers to some extent, but most of them are not hard-core bioinformaticians. They need to know much more, because they also have to grow cells, do the analytical measurements using the mass spectrometers and understand the mass spectrometers in order to maintain their performance.
That being said, I have to admit that 5% to 10% of the employees in my group are purely working with data. These are the bioinformaticians in the group. We also have some employees who write algorithms and a colleague who does all the data storage and all the software analyses of programs that we develop and write scripts for. We even have our own IT specialist in the group, because our work is so dependent on computers. That is why proteomics research is an integral part of the Utrecht Bioinformatics Center.
In my research group, we like to work together with researchers in different disciplines. What is so nice about the Utrecht Bioinformatics Center is that it focuses on information-driven research. Within the UBC, we can easily meet with people who may have similar questions that we face in proteomics, but they study genomics, metabolomics and bioinformatics. The UBC community is exactly what a successful data-driven Life Scientist needs.’

Sitting on a protein in a cell

‘My dreams are not limited to my own technology. Ideally, I would like to sit on a protein in a cell and just look around me and see what this protein is doing with all the other proteins and all other biomolecules in the cell, so I can really see how it is behaving. It’s like watching an individual in society and seeing how this individual acts based on his or her genetic background, but also how he or she interacts with the other people in society.’
’I want to be able to observe how proteins act in the context of their environment, and for proteins that context is the cell. We are gradually reaching the point where we are able to study that in experiments with mass spectrometry and complementary approaches.’

Changing boundaries of research

When asked for practical purposes of proteomics Albert tells: ‘I understand that people like to hear about short-term deliverables, but I am always a bit sceptical about that. Even the big Dutch health care charities, such as KWF and Hartstichting, want to fund more translational research that can benefit the patient tomorrow. We have put billions into cancer research, but there is still no real cure for it… so don’t expect me to come up with a cure for cancer tomorrow.’
‘Ultimately, it is not about tomorrow, but rather about helping the generation after us. I have more faith in our own approach: work on changing the boundaries of what can be studied by elucidating the mechanisms of diseases; how do they occur and develop.
I think we will never find a real cure for some diseases, but if we understand them better, we can manage them better. In my opinion, the power of fundamental research for the long-term perspective for medical needs is still underestimated, especially by the health care charities.’

Too curious for one research question

‘I am a technology oriented person. That means I don’t focus on a single biological research question; I am too curious for that. I sort of jump from one research question to the other. It is interesting to look at an old problem that people think has already been solved. When you look at it with a new tool, you’ll find new things and understand that nature is slightly or even completely different from what we thought before.’
‘I feel excited when we develop new tools, for instance to look at protein phosphorylation. That was very difficult just ten years ago, until we introduced a new technical tool which makes it much easier. Then we made a side-step into biology and tried to use the method to look at how cells are reprogrammed from stem cells into differentiated cells. But it was just as interesting for us to use similar approaches to find out how grass adapts to salt or how bacteria adapt from night to day. And then it doesn’t matter that much what the biological question is; for me it always comes to the same question: how does the world around us function at the molecular level?’

Reach out for the difficult things

‘My advice to young scientists and students is to not give up too quickly. Reach out for the thing that makes it easy for you to work hard and that seems difficult to obtain. Nowadays, too many people want the result at the end of the day. They want to be successful in the afternoon. I think it’s way more rewarding if you have to work for something for six months or even five years and then get a big benefit. That is so much better than being disappointed at the end of a day because a small thing you tried to achieve didn’t work.’
‘So I think you do not have to define your own goals to narrowly. Just go for the spontaneous opportunities that are out there, and then go for it with your whole heart and trust your gut feeling. For me, that attitude has worked out great. Most of the time, I am a very happy scientist who really enjoys his work.’