Universiteit Leiden

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‘Trying to learn as much as possible’

Dr. Alise Muok, originally from California, arrived in 2018 for her postdoc position in Leiden, at the Biology Institute. With a grant of the Dutch Cancer Institute (KWF), she is analyzing E. coli behavior in urine to determine the presence of a cancer marker, with her supervisor dr. Ariane Briegel.

Alise Muok has a degree in biochemistry. When she studied at Cornell in New York, one of the world’s leading technical universities, she worked closely together with Ariane Briegel, who was a postdoc herself at that time at CalTech in California. ‘I was specifically focusing on the biochemical characterization of proteins and their interaction outside the cell. The technique I used is called crystallography. For my Ph.D. I went to New York. Ariane got her lab at Leiden University, as she was appointed professor at the Institute of Biology. She wanted me to join her, but there were funding issues and of course I had to finish my thesis first.’

Nonetheless, the plan came together when Alise received a prestigious Marie Sklodowska-Curie grant upon her promotion. She and Ariane Briegel saw each other again in Leiden: a happy reunion. Alise’s postdoc position is for a period of four years; now being midway, she speaks very enthusiastic about her work, the people and the possibilities.

‘Now, in Dr. Ariane's Briegel's lab, I am continuing to study bacterial chemotaxis pathways, but with a different technique: electron cryo-tomography (ECT). With this method, we  literally freeze cells in ice and take pictures with specialized microscopes. With thousands of 2D pictures, we can create 3D structures that are then averaged to produce high-resolution models. We image tons of cells that way. This technique allows us to directly study microbes in their native state, visualizing individual proteins.’

‘Smart’ bacteria

Alise is eager to explain why this is so extremely fascinating – and helpful in daily life. ‘The interesting thing with bacteria is that they can move towards or away from certain environments. They have no brains nor eyes, yet they know exactly how to swim toward food or away from toxins. They have a chemical sense of knowing what to do and where to go, for example swim away from immune cells, being their natural enemy.

Understanding these structures and how they work, can help us to find new medicine and new diagnostic tests. For example, we know from our experiments that E. coli bacteria can sense human metabolites that are markers for cancer if found in urine. It is quite complex, but it comes down to the fact that E. coli possesses this function to navigate host tissues. Detecting these molecules in urine by utilizing E. coli swimming behavior will therefore identify the presence of the tumor marker. Currently, the tests that are in use are based on detecting the cancer marker itself after extraction from urine and therefore have to be performed in labs. These are expensive and time consuming. The E. coli pathway might be the key to faster and cheaper diagnosis. It also could be used to monitor the effectiveness of treatment and medicine: less E. coli attraction to urine means a decrease of the tumor marker as well.’

Unfortunately, due to corona, Alise hasn’t yet been able to get the research up and running. ‘We had planned to start on May 1st, working full time hours on this research project. We have completed all preliminary data, but the few hours we are allowed to work in the lab now are nearly enough to keep up the lab itself.’

Privilege

For Alise personally, this postdoc has broadened her expertise. ‘It is really a privilege to work with the exclusive ECT microscopes in Leiden. There are very few of them on this planet, but NeCEN, the dutch cryo-electron microscopy center, located at Leiden University, houses a few. My luck! I was specialized in crystallography, Ariane’s lab is specialized in ECT. These are two separate disciplines. It is highly unusual that you have an all-round experience in both methods. Therefore, I was very eager to get to know the for me new way of research. This has expanded my knowledge and skills; I have recently written a paper on the combined methods, which is now under review.

The other way around, I am planning on teaching one of the technicians in my group here to learn crystallography. This way, the expertise of the lab is growing and I can bring something new to the lab as well. The value of postdocs for the university is that they are highly motivated researchers. In my opinion, they form an essential part of the scientific community on campus. They strongly believe in what they are doing, and they can add to the expertise and the education of students by passing on their drive, knowledge and enthusiasm.’

Soft landing

For Alise, coming to Leiden was a long cherished wish. ‘I had always fantasized about going to Europe. And actually, it has not disappointed me at all: I just love living here. This city is so beautiful. I had a very soft landing. Ariane and her husband picked me up from the airport and they helped me out with a lot. My onboarding at the lab was great: I got the time and space to get to know it. That is so important, but I have heard stories of fellow postdocs experiencing the total opposite. At IBL, we work closely together, my colleagues are very supportive. Back home, I often heard that people in the Netherlands are not very friendly. But I guess they are mistaking straightforwardness for unfriendliness. I really like the Dutch directness.’

Even though her future is uncertain – this being one of the nastier parts of being a postdoc – Alise’s ambition is to fulfill a scientific position and have her own lab. ‘A lot of postdocs want that,’ she says, smiling. ‘As a student, I was learning the hard way: I messed up regularly. These situations turn out to be valuable lessons, because when I do an experiment now, I make sure I do it right. I feel so much more experienced and confident. But still, I am trying to learn as much as possible, every day. I would really love to stay here, in the Netherlands, if that would be possible. Or somewhere else in Europe. Scale-wise, America is bigger, but the European way of life suits me better. Every day life is so much safer, with more equality and better care. People tend to be more relaxed, with a healthier work-life balance.

Being a postdoc implies that you can make plans, but you cannot always execute them. How I cope? Doing things the best I can. If something doesn’t go the way you expect, don’t let it trouble you too much, as long as you have done your best. I always try disconnect mentally and to calm down. You cannot control everything. That is one basic law in science anyway. It’s always you versus nature.’

 

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