Author: Deleted User

Hello again everybody!

This is Rosa López again updating you about my internship as a HiLIFE Research Trainee! As you may remember (or not, please click here for the previous blog post 🙂 ) I used this scholarship to carry out my Master’s thesis as an international student at EPFL located in Lausanne (Switzerland). After six months of tough learning and hard work, I am delighted to inform you that my thesis is finished! In this blog post, I want to explain to you how the whole process ended, from the first experiments to the thesis submission. So, let’s dig in!

What was my thesis about? How was it performed?

As a quick recap of the previous blog post ( 😀 ), my Master’s thesis was performed at the Laboratory of Stem Cell Bioengineering (LSCB)¹. This lab, led by Prof. Matthias Lütolf, aims to develop third-generation organoids from stem cells by using innovative bioengineering strategies. One of the research lines focuses on the development of homeostatic human gastric third-generation organoids from human biopsies since this current organoid model contains several limitations². This project is being conducted by Moritz Hofer, a PhD student in LSCB and my supervisor throughout my whole thesis. So, you may ask: Rosa, what was your Master’s thesis about?

The main aim of my thesis was to test the effect of different extracellular matrix (ECM) proteins on gastric stem cell differentiation. The ECM is currently considered one of the key stem cell niche components^3,4. As a matter of fact, several ECM proteins had been already established to have a specific location within the human gastric mucosa. Thus, we wanted to check if these proteins could influence stem cell maintenance or differentiation towards one specific cell type. The main workflow of the project was to seed gastric organoid-derived epithelial cells on the proteins of interest and check for stem cell markers or other gastric epithelial cell markers with quantitative polymerase chain reaction (qPCR) after some time.

However, an important question arose right at the beginning of the project: how to perform this experiment? Some solutions could have been coating the seeding plate with the ECM protein of interest or using a mixture of Matrigel® with our ECM protein of interest. However, the former solution did not resemble the biomechanics of the mucosa, whereas the Matrigel® meant a too complex and uncontrollable environment. That is the reason why we decided to use synthetic hydrogels⁵, whose biomechanical properties can be modelled, and they are enriched only with our ECM proteins of interest. Even though it was a straightforward solution, a major part of the thesis was the bioengineering of synthetic hydrogel. The whole optimization took more than half of the internship! In the end, we were able to obtain preliminary results which showed that indeed some ECM proteins maintain stem cells, whereas others enhance differentiation towards other gastric cell types.

After all the experiments were done there was still one part missing… The whole thesis writing. I guess I am like most students, leaving all the writing towards the end. I would advise you to not do it. Although probably you’ll do the same mistake, so if you’re at that stage at this very moment… good luck!

And now, what is the next chapter?

My internship went on for six months and after I submitted my thesis, I got the Master’s graduation. During this time, I reassure myself what I want to do next: PhD. I still do not know where, but I know for sure that I like stem cell research. In the next months, I will be doing another internship before the PhD focused on the scarring and repair in the central nervous system at Karolinska Institutet. Let’s see how that goes and how it affects my future!

 

 

I would like to finish this post by acknowledging all the LSCB team, and specifically thanking Moritz Hofer for all his help and mentoring during this internship. I believe that having good mentoring is essential for success! Also, to all the people that were with me during the whole process, either physically in Switzerland or through the phone. Emotional support is more than necessary to complete a good thesis. Last but not least, thanks to Switzerland for having such breathtaking nature and landscapes. Although long hours in the lab are necessary, having some getaways is as important. I will bless you with some Swiss pics down below 😀

Thank you all for reading! Hope the best for you :3

Bests,

Rosa

 

Some (maybe) interesting links: 

1. Laboratory of Stem Cell Bioengineering Webpage: https://www.epfl.ch/labs/lutolf-lab/
2. Seidlitz, T., Koo, B. K., & Stange, D. E. (2020). Gastric organoids—an in vitro model system for the study of gastric development and road to personalized medicine. Cell Death & Differentiation, 28(1), 68–83. https://doi.org/10.1038/s41418-020-00662-2
3. Pardo-Saganta, A., Calvo, I. A., Saez, B., & Prosper, F. (2019). Role of the Extracellular Matrix in Stem Cell Maintenance. Current Stem Cell Reports 2019 5:1, 5(1), 1–10. https://doi.org/10.1007/S40778-019-0149-9
4. Rezakhani, S., Gjorevski, N., & Lutolf, M. P. (2021). Extracellular matrix requirements for gastrointestinal organoid cultures. Biomaterials, 276. https://doi.org/10.1016/J.BIOMATERIALS.2021.121020
5. Madduma-Bandarage, U. S. K., & Madihally, S. V. (2021). Synthetic hydrogels: Synthesis, novel trends, and applications. Journal of Applied Polymer Science, 138(19), 50376.  https://doi.org/10.1002/APP.50376

Hello everybody!

My name is Rosa López, and I am delighted to be one of the 2022 HiLIFE Research Trainees. In this post, I would like to introduce who am I and what took me to this life stage, as well as my interest in science and my current research topic. That said, let’s go deep into the matter!

Who am I and how did I arrive at this point?

I am a young scientist who graduated in Biomedical Sciences at the University of Barcelona in 2019. However, my last year of the degree did not take place in my hometown since I was granted an Erasmus Scholarship to carry out my final degree project at the University of Helsinki. For nearly a year, I got to study the molecular mechanism of ageing in Saccharomyces cerevisiae, also known as yeast; in Prof. Juha Saarikangas’ laboratory. One year later, when I was already addicted to Helsinki and its landscapes, I got accepted into the Master’s program of Genetics and Molecular Biosciences (GMB) at the University of Helsinki. Within this program, I decided to pursue the Cell and Developmental Biology study track since my main interests lie in stem cell biology, regenerative medicine, and cellular ageing. Several lectures about regulation mechanisms of stem cells were enough to encourage me to search for laboratories whose main research topic was stem cell regulation. This decision led me to my current point, I am a Master’s thesis student at the Laboratory of Stem Cell Bioengineering (LSCB) at EPFL, the Swiss Federal Institute of Technology in Lausanne. I was thrilled when Prof. Matthias Lütolf awarded me with this position at his laboratory. Additionally, for this traineeship, I was awarded the HiLIFE Research Trainee Scholarship issued by the Helsinki Institute of Life Sciences (HiLIFE) which provides financial support, as well as promotes scientific communication to the public. I would like to state that I am highly grateful to the Selection Committee for considering me as a fit candidate for this position.

What am I exactly doing at the LSCB and what is my main research topic?

I would like to start this part with a bit of scientific background to give you a grasp of the whole picture. Nowadays, the term ‘organoids’ is quite known in the scientific community and refers to a 3D multicellular in vitro tissue construct that mimics its corresponding tissue in vivo¹. Although organoids are being used around the globe and for several purposes, there are some limitations in this methodology. First of all, since they are a 3D structure, they are usually embedded in a Matrigel matrix whose origin is from a mouse sarcoma basement membrane and has a high batch-to-batch variability². The Matrigel origin abolishes the possibility of its usage for regenerative medicine in humans, and the batch-to-batch variability interferes with the experiment reproducibility. Additionally, while some organoids are more characterized than others due to their tissue of origin, none of them keeps a physiological tissue shape, nor an unlimited functionality or a high lifespan³. To solvent these limitations on organoid culturing, the LSCB laboratory’s main research goal is to develop third-generation organoids from stem cells by using innovative bioengineering strategies.

My contribution to the lab’s main goal is to test the effect of different ECM proteins on gastric stem cell differentiation and regulation. Human gastric organoids are not as well characterized as human intestinal organoids, as a matter of fact, not all the cell components of the human gastric glands are able to be differentiated in the common 3D organoid model⁴. On the other side, the focus on the extracellular matrix (ECM) as a key niche component of stem cells has exponentially increased in the past years^5,6. Therefore, I am researching whether bioengineering a synthetic hydrogel enriched with different ECM proteins can modulate human gastric stem cell regulation and differentiation to improve the pre-existing 3D organoid model.

Even though I started this journey last November, it is still not finished! Impressive things are yet to come, and I expect to have interesting results by the end of this internship. I will keep you posted! In the meantime, you can also check HiLIFE Research Trainees’ social media for more daily life stories 🙂

I am particularly obsessed with citing, so down below you have some references of what I just stated in case someone wants to go deeper on the topic!

1. Souza, D. N. (2018, January 3). Organoids. Nature. Retrieved February 23, 2022, from https://www.nature.com/articles/nmeth.4576?error=cookies_not_supported&code=14fb20f7-ab18-46ff-8850-9eaae3e3281e
2. Serban, M. A., & Prestwich, G. D. (2008). Modular extracellular matrices: Solutions for the puzzle. Methods, 45(1), 93–98. https://doi.org/10.1016/j.ymeth.2008.01.010
3. Hofer, M., & Lutolf, M. P. (2021). Engineering organoids. Nature Reviews Materials, 6(5), 402–420. https://doi.org/10.1038/s41578-021-00279-y
4. Seidlitz, T., Koo, B. K., & Stange, D. E. (2020). Gastric organoids—an in vitro model system for the study of gastric development and road to personalized medicine. Cell Death & Differentiation, 28(1), 68–83. https://doi.org/10.1038/s41418-020-00662-2
5. Pardo-Saganta, A., Calvo, I. A., Saez, B., & Prosper, F. (2019). Role of the Extracellular Matrix in Stem Cell Maintenance. Current Stem Cell Reports, 5(1), 1–10. https://doi.org/10.1007/s40778-019-0149-9
6. Rezakhani, S., Gjorevski, N., & Lutolf, M. (2021). Extracellular matrix requirements for gastrointestinal organoid cultures. Biomaterials, 276, 121020. https://doi.org/10.1016/j.biomaterials.2021.121020