Paving a route for the PhD project “Obesity Curiosity” – reflections on a traineeship in Dr Merkle’s lab

Photo: Our world in Data map (cc) about Obesity in adults, full access: https://ourworldindata.org/obesity

Suvi Laitinen, 21, researcher and MD-PhD-student left for a research exchange right after completing her second year of medical school and returned to Finland to start her third year in mid-August. Her grant was awarded exceptionally for 2.5 months, taking into consideration the attendance requirements of her medical school. She completed an international exchange in Dr Florian Merkle’s lab at the Institute of Metabolic Science (IMS) at the University of Cambridge. Her project Obesity Curiosity is focused on understanding the relationship between hunger, satiety and obesity (Project introduction video here: https://www.youtube.com/watch?v=C0dseCj4a9g )

Laitinen worked in biosafety level 2 stem cell culture, learning Dr Merkle’s lab neuron differentiation protocol and testing her differentiation protocol for organoids built on existing protocols. Dr Merkle has pioneered in differentiating human induced pluripotent stem cell-derived functional human neurons. “That work has been a game changer – thanks to his work efficient production and the study of the live human brain is possible for hypothalamic key neurons – and his team has continued the work towards applications with stunning results!”, Laitinen describes with visible enthusiasm.

She praises the supervision she received: “In addition to innovative and supportive supervision from Dr Merkle, I had the honour to learn from the brilliant postdoctoral researcher Dr Cortina Chen. Her precision, efficiency and ability to handle multiple projects at the same time is astonishing. Moreover, she welcomed me and my questions warmly to her busy schedule, took time to teach me and helped further develop the methodology for my project. I am very grateful for Dr Chen – not only was she a fabulous immediate supervisor with great leadership skills, she made me feel supported and well on track every day – and also a kind and relaxed person from whom I learnt immensely. It was wonderful to work with her!”

Results from Laitinen’s work were living organoids that then were collected as samples that are the base for her PhD project. “I am immensely grateful to Dr Merkle for warmly welcoming me into his lab and for his ongoing advice and support which has been highly impactful for my project. I have now an idea of how to continue with my research when I return to Finland. The exchange has been a wonderful experience and will stay with me for all my life!”

Laitinen reminds all aspiring young researchers to pay attention to the institute as well when thinking about where to apply: “I was so happy to have both amazing lab and institute. IMS is an amazing place – brilliant, passionate people all working in the same field in the same laboratories. The institute is indeed one of the hot spots of obesity research, and they have amazing internal and external speakers with a full auditorium almost every week. The institute also excelled beyond the academic measures, everyone was welcoming and helpful. Huge thanks to all PhD and Masters students I met, you are amazing and your great team spirit is something I am gonna miss. It was a huge privilege to be part of the community for a short period”.

During her stay, she also had the opportunity to build connections with and seek advice from the other lead scientists in the field. “I want to express my deep gratitude to Dr Madeline Lanchaster, Professor Sir Shankar Balasubramanian and Professor Sir David Klenerman for taking time from their undoubtedly very busy schedule to meet me and answer my questions”.

Dr Madeline Lanchaster pioneered by publishing first brain organoid protocol in 2014 and now leads a lab in the MRC Laboratory of Molecular Biology on brain development in cerebral organoids. Laitinen visited her lab and had a deeply impactful discussion on different approaches in brain modelling. “Dr Lanchaster’s insight into deciding between gardening and engineering approach for brain model composition was eye-opening for me and I believe her advice will benefit the project for a long time”.

Professor Sir Shankar Balasubramanian and Professor Sir David Klenerman won the Millenium Prize in 2020 for Next Generation DNA Sequencing, awarded by the Technology Academy of Finland (TAF), which also awarded Laitinen and Maula Millenium Youth Prize 2019 for their project proposing a solution that could theoretically slow down Alzheimer’s disease.

Professor Balasubramanian leads world-class research on unconventional DNA complexes and the start-up branched from their research is currently investigating those as a treatment for human diseases. “Professor Balasubramanian had amazingly organized an exciting half a day for me to meet both his lab members in Cancer Research UK (CRUK) and at the Department of Chemistry and I met so many exciting people and changed ideas. His advice for me on how to build a research program in a smaller country like Finland and his supportive approach was incredibly helpful!”

Professor Sir David Klenerman leads a research program on imaging single molecules with complex microscopy techniques. In his lab, Laitinen saw first-hand imaging of single protein aggregates associated with neurodegenerative diseases. “I can only try to describe the awe I experienced looking at the microscope capable (with physics I am not able to explain) of visualizing individual protein complexes. Those are on a nanometer scale and it is wonderful that they have stretched the capability of technology to this level! Professor Klenerman also gave useful advice on how to bounce back after mistakes and unsuccessful events that are inevitable in science despite our best efforts especially when trying to do something completely new. Most of the time things don’t work out the way we expect them to just because they are so new”.

Laitinen describes how the research exchange in an international lab was a formative experience for her. “Traveling to Cambridge enabled me to take my project to the next level and strengthen our scientific collaboration with Dr Merkle’s lab. I learnt about exciting research done in the lab and IMS as well as other labs that welcomed me to visit. Joining one of the forefronts of my research field has been incredible and I cannot emphasise enough how impactful meeting all these brilliant people from all career stages joined in Cambridge from around the with the common goal of the best possible science has been”.

Laitinen points out how crucial the support of Helsinki Institute of Life Science (HiLIFE), an independent life sciences research institute within University of Helsinki was for her experience. “HiLIFE supported me with my ambitious idea to explore something that nobody has investigated this way before. In the interview part of the multi-step application process – which by the way I think is an amazing investment of theirs to teach young scientists how to present their ideas and take that challenge of answering to a whole board of experts – I was asked if I could acquire another funding for the summer exchange. As I told them, I am fighting with all my effort for my project, still without preliminary data and restricted funding opportunities for this early career stage, I don’t think it would have been possible. HiLIFE Undergraduate Student Research trainee Scholarship is a unique opportunity and for me, it was impactful beyond measure. I think the exchange set me well for the coming years of PhD research and given me skills that I will be able to use long in my efforts to build my research program in Finland. I humbly thank you for this opportunity”.

Earthworms as the ultimate strategy to face microplastic pollution

Have you ever seen an earthworm make magic? These little creatures can, for instance, eat leaves and make them disappear! Earthworms are one of the few animals capable of decomposing organic material. So, even though they seem insignificant living things, it is hard to imagine a world without them. But, what if I told you earthworms could also make microplastics in soil vanish? What if they represent the ultimate strategy to face microplastic pollution?

I am Mireia Pagès Guitart, a Catalan biomedical scientist, a second-year student of the Master’s Programme in Pharmaceutical Research, Development and Safety at the University of Helsinki, and a new HiLIFE trainee! With the support of the HiLIFE Research Trainee Scholarship, my ambition was to engage in applying sustainability to science, a much-needed climate action.

Me working in the lab, performing a Western Blot. If I had known what my future research would be like back then, I don’t know if I would have believed it!

Even though my passion has always relied on combining both topics (sustainable science), this dream didn’t come true until I came upon Prof. Michael Jeltsch. He is another scientist fond of practicing sustainability, both in his lab and his research projects. What amazed me the most was the earthworm project that his lab team wanted to carry out: using earthworms as a microplastic degradation strategy.

Earthworm’s digestive system and microbiota

Before joining the group’s lab work, I did an extensive literature review on the earthworms’ digestive system and microbiota. This was useful to expand my background knowledge and have some insights on how to conduct the experimental part of the project.

Earthworm’s digestive system is mainly composed of the gizzard. The gizzard is an amazing structure responsible for grinding and crushing the food. Different digestive glands are also present and contribute to the digestion process by releasing proteolytic enzymes. In other words, these enzymes break down the ingested food into even smaller pieces.

Inside the earthworm’s gut, there is also the microbiota: a community of bacteria. The microbiota maintains the intestinal homeostasis and, most importantly, breaks down carbohydrates that the glands can’t digest, contributing to the digestion process further.

Surprisingly, it has been seen that the earthworms’ digestive system and its microbiota digest contaminants from the ground along organic material. Could this mean that earthworms would be able to turn microplastics into soil fertilizer? Indeed, this would be a promising approach to explore.

Two little creatures of our earthworm farm in the lab. They are making magic 😉
Picture taken by Michael Jeltsch

Microplastic degradation potential

On my first day in the laboratory, we designed the experimental plan. To make our dreams come true (creating microplastic-degrading earthworms), we should exploit the earthworm’s digestive system properties. For instance, if specific enzymes released by their glands are more effective than others, we could enhance their expression to improve the digestion process.

Overall, it was clear that we would need to modify the earthworm’s DNA to make them transgenic animals. Let’s imagine that we aim to enhance the expression of a certain enzyme. We would take the gene coding for such an enzyme, assemble it in a plasmid (=DNA) and place this plasmid inside a virus. This is known as a cloning step. Next, we would transfer the plasmid inside the earthworm by infecting the animal with the virus. Once inside, the earthworm would express the gene and activate the enzyme production. Finally, we would assess if the microplastics’ degradation takes place.

Gene expression and regulation: Overview of DNA Cloning, 2018 (Khan Academy): http://tinyurl.com/229ub9xb

The beginning of my research

Of course, every experiment needs a control before anything happens. For this reason, since I started my traineeship, I have made the mentioned cloning step with GFP protein instead of any enzyme gene (previous example). GFP protein is easy to detect on animals because it expresses green fluorescence. Using GFP will be useful for us to know if our experimental method on earthworms works at all: earthworms will emit green fluorescence if we are successful. If we are on the right track, we will be able to proceed with the rest of the project afterwards.

During this time, I have also got to know the lab team members and how they work. I give lots of importance to team building, so I am happy to feel that comfortable in this group. I have high expectations for all that I will learn, the lab techniques I will use and the skills I will earn. This traineeship will help me grow both as a scientist and as a person. And, if this project raises meaningful outcomes, we would have a powerful tool to fight one of the biggest issues that we are facing nowadays:  microplastics pollution. 

Studying in Finland is a worthwhile adventure. The snow gives light in the darkest times and the sun is much more appreciated than anywhere else. Also, the University of Helsinki provides plenty of opportunities to keep learning in the best way. All in all, it is an unforgettable experience. You will hear more about my traineeship experience and the research progress later this spring. Keep an eye out because there is more to come!

Again me, this time in nature, looking at sunflowers that probably have bloomed thanks to our little helpers, the awesome earthworms!