International HiLIFE Trainee: Addicted to Country Hopping

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?

Me during a not-so-hot summer day in Helsinki

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 years5,6. 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

A journey to understand SARS-CoV-2 neutralization through cryoEM

Hello!

My name is Rupesh, and I’m a second-year master’s student studying in the Biochemistry and Structural Biology study track of the Genetics and Molecular Biosciences program at the University of Helsinki. I come from Chennai, a beautiful city in the south of India. I did my Bachelor’s in Biotechnology in Chennai and graduated with an engineering degree, B.Tech. For as long as I can remember, I have been drawn towards Molecular Biology and Biochemistry. And so, for my bachelor’s thesis, I worked in a virology lab at the CSIR – Centre for Cellular and Molecular Biology in Hyderabad, India. I thoroughly enjoyed my time there and developed an appetite for research, in viruses and molecular biology to be precise.

I started my master’s studies at the University of Helsinki in 2020, and in the very first semester, there was this one course which I really liked: GMB–105 Introduction to structural biology and biophysics. Being a part of that course felt refreshing and I still remember saying to myself, ‘When I have to search for labs to do my master’s thesis, I am going to ask the structural biology labs first’. And that is exactly what I did a few months back. I reached out to Dr. Ilona Rissanen and Prof. Juha Huiskonen who are working on structural virology and structural biology of macromolecules and interactions respectively. It was a fruitful attempt, as I got the opportunity to work on a short-term research project on the development of protein scaffolds for cryogenic electron microscopy (cryoEM) under their supervision at the Institute of Biotechnology.

Currently, I have just started working on my master’s thesis project, happily continuing under their supervision. My project is aimed at discovering the structural basis of SARS-CoV-2 neutralization by an antigen-binding fragment (Fab) from a patient-derived monoclonal antibody that targets the spike protein. I will use single-particle cryoEM to elucidate the molecular architecture of the Fab-bound spike protein trimer and identify the epitope of the Fab. The project benefits from a thriving collaboration with the iCoin consortium, funded by the Academy of Finland, which aims to isolate SARS-CoV-2 neutralizing antibodies from Finnish COVID-19 patients to further the research on virus inhibition by the humoral immune response.

I could not have asked for a better environment to guide me in carrying out this project. I got familiar with some of the techniques and protocols that will be used in my thesis during my short-term project. I hope to build on those skills and hone them even further, especially in making and handling grids for cryoEM.

I’m honored to have been chosen as a HiLIFE research trainee. The research standards are set incredibly high at the University of Helsinki, which makes this traineeship even more prestigious. With the support from HiLIFE, I believe I can do amazing science, learning from the experts. Hopefully, this is the beginning of an exciting journey in research!

I will be back later this spring to share some exciting results with you. Until then, take care!

Rupesh

Human stem cells and puberty

Hi everyone,

I am Linda, a second-year Master’s student in the program of Genetics and Molecular Biosciences at the University of Helsinki. As one of the 2022 HiLIFE Research Trainees, I am very happy to be able to follow my scientific curiosities in the upcoming months. I applied for the HiLIFE Research Trainee scholarship to gain experience in the field of stem cell biology and cell culture, and I am excited to have found a suitable opportunity for this in the Raivio lab at Biomedicum. I have recently started working on my thesis project. Within the following months, I will learn more about the genetic and hormonal regulation of puberty initiation. The Raivio group is specialized in the differentiation of human pluripotent stem cells into GnRH-releasing neurons, which are crucial for puberty induction.

My study background is in Genetics and Genomics and during my thesis project, I will gain more practical experience in related methods such as cloning, gRNA design, and using the CRISPR/Cas9 technology. My general goal is to activate the expression of target genes associated with puberty. However, I am also thrilled to learn about new techniques and expand my skill set in the upcoming months. Especially, stem cell biology, cell culture, and neurobiology are fields I am excited to get in touch with. Also, during my first weeks working in the lab, I was able to attend the STEMM Research Program Retreat which has been a new and exciting experience for me. It helped to find out what the current hot topics in stem cell research are and to learn more about ongoing projects of different labs. Additionally, it was also a great opportunity to socialize with colleagues.

After working in bioinformatics from home during the past year, I am highly excited to be able to visit the campus and lab on a daily basis now. Despite the pandemic, I can conduct experiments and exchange ideas with other members of the team. I am very thankful for the support I was awarded with by HiLIFE, as well as for the position I received in the research lab. I am hoping to learn and develop skills for my future career, but also to enjoy my time at Biomedicum. You’ll hear from me again soon.

To fear or not to fear: understanding the world of the Reed Warbler

Hi all!

My name is Sarella Arkkila and I am a second year masters student in Ecology and Evolutionary Biology at the University of Helsinki. I did my bachelor’s in Animal Behaviour at the University of Aberdeen and knew that this is what my passion lies in. Coming to the University of Helsinki, my search for a research group studying animal behaviour began. I found the amazing Information Ecology and Co-evolution research group ( https://www2.helsinki.fi/en/researchgroups/evolution-sociality-behaviour/information-ecology-co-evolution ) led by Prof. Rose Thorogood and knew that this is where I wanted to continue my career within biology. I was honoured to be allowed to join the research group.

My thesis work is on the effect of the landscape of fear on the parenting behaviour of the Eurasian reed warbler. Landscape of fear (LOF) is how animals view their surroundings and the different risks associated within that surrounding. There are several factors that contribute to the LOF, such as the perception of the risk of predators and parasites. LOF in turn influences an animal’s behaviour in different areas of its habitat. For example, in an area where an animal perceives the predation risk to be higher, they may exhibit more vigilance behaviour. These changes in vigilance behaviour can influence foraging efficiency and parental provisioning, as the focus is on spotting and avoiding predation, which can ultimately affect an animal’s fitness. The study of LOF is crucial especially now that environments are changing rapidly, and where new pressures arise and the survival of species within their new or existing habitats are uncertain.

Within the concept of LOF, a few studies have been done on how changes in perceived risk of predation impact indirectly on fitness, but perceived risk of parasitism is yet to be tested. The common cuckoo is a brood parasite, laying its eggs in other species’ nests, one of which is the reed warbler. The reed warbler changes its behavioural defences when it perceives that it is at greater risk of parasitism by cuckoos. This behavioural change can either result from direct observations of seeing a cuckoo or from social information from neighbouring birds attacking a cuckoo in its nest. However it is unknown if this perception of greater risk of parasitism has indirect and long-term effects on behaviour, ultimately affecting the quality of parenting.

Looking for Reed Warbler nests within the reeds around Helsinki.

To understand the impact of the LOF from parasitism, I conducted fieldwork with the research group in the summer 2021. As part of another experiment, we manipulated the social information (SI) that the birds received about cuckoos by using model nests (previously collected nests), threats (painted 3D models), and alarm call playbacks. I then compared their ‘fear-type’ behaviour both during the presentations and afterwards to birds presented with alarm calls but an innocuous ‘threat’ (a teal), or to ambient teal calls as a control. I collected behavioural observations from video recordings at the nests, which gave me a ‘reed warbler’s perspective’ that could not be gained by observing the birds in person. To evaluate the long-term impact of the LOF, I then recorded parental behaviour 6 days later during incubation, and then again once the chicks had hatched.

A reed warbler incubating its eggs, a screenshot taken from an incubation video.

For my Master’s thesis, I have been watching a sample of these video recordings to determine how socially-provided information about parasitism risk influences behaviour. Thanks to the HiLIFE traineeship, I can now dive deeper into the videos to find out more about the longer-term effects of fear and publish a scientific article on the findings. I hope to be able to share the study results with you after this fantastic HiLIFE traineeship period. Wish me luck!