From the Computational World to the Experimental Reality - The Journey, a blogpost by ESR3 Varbina Ivanova
Secondments are an essential part of our scientific journey as Early-Stage Researchers in the ALLODD ITN consortium. Essentially, they are research stays, carefully planned by our supervisors to both complement our Ph.D. projects and give us experience and expertise in different fields than ours. It is a time to gain new knowledge, acquire new skills and network with people from outside your line of research. It gives us a chance to see the bigger picture in science and discover the numerous possibilities in Allostery and Drug Discovery.
In my case, my first secondment journey was from red-hot Barcelona to 10-degree Stockholm; from my familiar computational world to the not-so-familiar and complex reality of wet-lab experiments.
Imagine a computational chemist with a background in chemical engineering having to express and purify their first protein. That was me 6 months ago. Very excited, a little scared, optimistic and ready to learn. My experimental journey began in the group of Dr. Galdeano, at the University of Barcelona, where I was taught how to grow bacteria, how to express protein and how to purify it. I am extremely thankful to my colleagues from Galdeano’s lab, Roger and Andrea, for their patience with me and my rusty experimental skills. With their guidance, soon my protein was ready for shipping to Karolinska Institute, to the Mass Spec lab of prof. Roman Zubarev. Together with the protein, I shipped myself to Sweden, leaving aside my computational studies and embracing my new challenge: the world of the MS techniques.
For the next three months in the lab at Karolinska Institute, I learned something new every day- not only about the MS experiments but also about the experimental work style. During the first few weeks, together with my ESR colleague, Bohdana Sokolova, I was trained on how to prepare HDX-MS samples, how to handle MS instruments and how to analyze MS data. Along with the HDX-MS methodology, I also learned experimental design from A to Z, planning based on instruments’ availability and lab time organization. It was a time of everyday lessons; some were easy and some were hard.
The hardest lesson for me was accepting that experiments don’t always work out. My optimism wavered when my first HDX tests did not give the expected results. My hopes diminished as we stumbled upon drawback after drawback. Sometimes the established experimental technique works perfectly for your project, but other times it needs parameters’ optimization and even further development to meet the needs of the scientist. Even then, the method may not provide the results it did in others’ research and it may even lead to a dead end. But I learned this is okay! I understood failure is a natural part of the experimental process and it is essential to be aware of the opportunities and the limitations of each technique. With every method mastered you also gain experience on how and when to use it and this lesson will always stay with me.
In the line of learning and acquiring new skills, my experimental journey did not end with the HDX-MS technique. With Dr. Gaetani’s guidance, I set off to gain experience in the Proteome Integral Solubility Alteration (PISA) assay, developed in Zubarev’s lab.
Now imagine a computational chemist in a cell lab- again, that was me. It was not easy at first- everything about the cell lab was new to me; every skill, every piece of information sounded foreign. And, of course, I did make some mistakes. But each mistake turned into a lesson. Through trial and error, through practice and patience, in the last week of my secondment, I felt like a well-oiled machine with tissue culturing and cell treatment. And it was likewise with every other part of the 5-day PISA procedure I had to master to be able to perform the designed experiments.
It was an amazing experience- careful planning each day according to the instruments’ availability; getting familiar with many different practices; working on a tight schedule with many tasks. Some days nothing was working, some days went smoothly and exactly as planned- a true experimental rollercoaster. And just like that, I conducted the planned PISA experiments and my secondment journey came to an end. I felt a huge sense of fulfillment- the three months experimental stay in Stockholm has turned me, a computer-based young scientist, into an experimentalist. I wouldn’t say that now I am an expert on MS-based methods; but I am sure the skills and experience I got from Karolinska Institute will help me through the next steps of my career and I am grateful for this opportunity to everyone involved.
Now that I am back to my computational studies, I am looking forward to my next secondment and to learning more about the experimental part of drug discovery. And I would recommend to every computational scientist that hasn’t been in the lab for a long time- go out of your comfort zone, make the journey and experience research from the other side. It is worth the rollercoaster!
And some unforgettable moments from the journey (whenever I remembered to take a photo)!
Here we are, it's been a year since I started the ALLODD journey… and what a year!
In January 2022 I settled down in Germany, which administratively was not so smooth. After a few days, I officially started in the lab at the biggest site and also headquarters of Merck. It is like a small town (we are more than 12´000 people working there). Despite being the only non-German speaker in the lab, any single person speaks English, which made my first months a lot easier that I would expect by being somewhere you don’t speak the language. Actually, I learned German at school a few years ago and let me say it is not like riding a bike you will forget if you do not practice! I hope, by the end of the project, to be able to speak fluently in German. This is also why I applied to learn more scientifically and personally.
As the first weeks and months go by, I was learning more about the different machines in the lab and their corresponding assays, as well as going deeper in the literature.
September was the opportunity to go to Barcelona in Prof. Dr. Curutchet lab as my first secondment. Moving from Darmstadt to Barcelona was definitely a weather improvement. Even though the surroundings were not new for me, I discovered there a new scientific world: the computational world. From opening a terminal to running my first molecular dynamic simulation, it was a very broad journey. This was also my first experience working at the University, as I did all my internships in private companies. I enjoyed my stay in the group, I am very thankful for the time they devoted to me, to explain and help me or to discover new restaurants.
Now back in Germany, it´s time for me to be reunited with the lab experiments and my cells: Saccharomyces cerevisiae. Yes, those are the same cells used in bakery or brewery (I had to adapt to the German culture 😉).
Being part of an ITN also means business-travel, during this first year, we met in-person twice with the wonderful people of the ALLODD network. Vienna, Barcelona and soon Strasbourg and Budapest, we emphasized the words network and partnerships!
The best is yet to come!