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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
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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

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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.

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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!

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HiLIFE TRAINEE ATTENDING THE ASHG21 ANNUAL MEETING

Hi fellow students! My name is Celia Gómez Sánchez, and I am a second-year master’s student in Genetics and Molecular Biosciences. In October 2021 I received the opportunity to attend the American Society of Human Genetics (ASHG) 2021 annual meeting. The conference was held in the US with a hybrid model, so attendees could watch the talks either on-site or online. This enabled people from all over the world to participate ¬–including me. Because there were multiple events happening simultaneously, during the week when the ASHG21 meeting happened I only attended the talks I was most interested in; nevertheless, the conferences were recorded, so they were later accessible to everybody like me that could not watch them live. This was a great feature since I was very keen on most of the topics, and wanted to make the most of this opportunity 😀

As a master’s student, I didn’t present any type of research, I only listened to the conferences. However, this was enough to learn a lot of about various topics, some of which were closely related to my master’s thesis that I’m currently working in. I was especially interested in genetics and neurosciences, and the talks concerning neurodevelopmental diseases were definitely my favorites. We learnt about the use of both cells and mice as models for the different disorders, and how they had explored the genome to find disease-causing variants. For example, one of the groups were able to identify autosomal recessive variants in genes previously unlinked to autism spectrum disorder, resulting in 31% rate of patient diagnosis. Furthermore, the talks explained the use of genomic techniques that I had recently studied (such as single-cell ATAC-seq or single-cell transcriptomics), which provided me with a great opportunity to understand better the application of these techniques with real examples and the results they provide with.

Moreover, some of the meetings specifically focused on craniofacial development, my area of research at the moment. I am studying the cranial neural crest (that gives rise to the craniofacial region), and certain conditions related to defects arising from it, such as pituitary hormone deficiency and maternally inherited gingival fibromatosis. These conditions result in delayed growth and puberty and craniofacial malformations. What is very interesting about the neural crest is that 30% of all congenital malformations in humans are derived from abnormalities in it, since the neural crest precedes the formation of multiple tissues in the embryo. Therefore, its study is key to preventing and treating multiple birth defects, and so I was very excited to learn about state-of-the-art research involving this embryonic structure. As a matter of example, I was glad to hear about TFAP2A, a cranial neural crest marker on which I have been focusing my experiments. I learnt that enhancer mutations that dysregulate this gene were found to cause branchio-oculo-facial syndrome (BOFS), a condition that results in eyes and ears malformations together with characteristic facial features.

In conclusion, being able to attend the ASHG21 meeting was a very powerful experience, that allowed me to learn about multiple topics of interest and get in touch with current methods to research human diseases. I am very happy to have been able to attend these conferences and I really thank HiLIFE for this opportunity, that I wouldn’t have been able to get on my own.

Celia Gómez Sánchez

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Attending ESOT-congress as a HiLIFE-trainee

 

Hi, and welcome to the HiLIFE-trainee blog! My name is Akseli Bonsdorff and I am a fourth-year medical student at the University of Helsinki and also working on my PhD-thesis in pancreas transplantation and general pancreatic surgery. My first scientific article on the role of early plasma amylase levels in predicting pancreas graft-related complications after pancreas transplantation was published in early 2021 and I received an opportunity to present the key findings of the study at the European Society of Transplantation (ESOT) 2021 congress. ESOT is a biannual congress that brings together transplantation surgeons, nephrologists, hepatologists, pathologists, nurses, and students – such as me – and acts as a platform for discussing novel topics and state-of-the-art findings in the field of transplantation.

This year, ESOT was held as a hybrid conference, and attendees had the chance to choose between on-site or online attendance. For approximately ten to twelve hours a day, I sat and listened through the many inspirational talks, keynotes, presentations, and discussions on topics ranging from the definition of brain death to the implementation of artificial intelligence applications in transplant organ allocation systems, and from the effect of Covid19 on the transplant communities to why living donor liver transplantation is not performed extensively in Western countries but cover the majority of liver transplantations in Asian countries. I am still dumbfounded by the exhaustive coverage of different topics, and probably still- after two weeks from the congress – processing all the new knowledge I gained.

On the third day of the congress came the moment of my presentation. Due to the hybrid model, I had to prerecord the bulk of my presentation and my role during the session was to answer questions arising from the audience on-site and online. The two dutch professors chairing my session were not too harsh on me, and one of them even thanked me for an interesting presentation (which he did for every presenter, but needless to say, it felt nice at the moment). Hybrid or not, my debut was something I will remember for a long time.

Without a doubt, ESOT2021 had provided me everything I expected and probably even more. I had the chance to delve deeper into my own field of research (that being pancreas transplantation), but also received tasters into the other subspecialties in transplantation. I am extremely grateful for the financial and scholarly help from my great mentors Adj. Prof. Ville Sallinen and Adj. Prof. Ilkka Helanterä. I also thank HiLIFE for the support received. Making attending an event like this possible for students and aspiring researchers is extremely appreciated.

Akseli Bonsdorff

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Fireballs of ischemic stroke

Hi Everyone!

My name is Katariina Järvinen, and I am a second-year master’s student in the Translational Medicine program at the University of Helsinki. I conducted my master’s thesis research during summer 2020. One of the aims of my project was to evaluate the potential of different phagocytosis related genes on enhancement of microglia phagocytosis.

Working as a HiLIFE research trainee in Mikko Airavaara’s research group, I learned many new skills, for example culturing of cells, and gained valuable practical experience from working in a laboratory. In addition, I was able to widen my professional network. Overall, I was impressed with how the whole group works together: if something doesn’t go as planned, there is always help available and multiple people giving ideas on tackling the issue or guidance in proceeding with another suitable method.

Here is a picture of BV2 microglia 1 hour after adding phagocytosis bioparticles. Inside the cells the bioparticles react to pH change and give red fluorescence signal.

Being HiLIFE Research Trainee met all of my expectations despite COVID-19 restrictions. I’m happy that I got to do my traineeship in a research group that is doing research that excites me and that my project has high scientifical value to the members of the group. The results gained during the traineeship will be validated in ischemic stroke in vivo study.

I am deeply grateful to Mikko Airavaara and my supervisor Helike Lõhelaid for their support and guidance during my traineeship and after it. I would also like to thank HiLIFE for supporting me in my early career in medical research.

Here you can read more about neuroprotection and neurorepair group.

Katariina Järvinen

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Leiomyomas, bioinformatics, a little bit of lab work and wonderful people

Circos plot

Hi, all of you reading this HiLife trainee blog! I am Vilja and I am a master’s student in genetics and molecular biosciences. At the beginning of this year, I was looking for a master’s thesis position, and I wished to find a project related to cancer or other tumors. I also wanted to further develop my skills on bioinformatics. I was super excited to get a master’s thesis position at Pia Vahteristo’s research group studying gynecological tumor genomics. I was supposed to start with my master’s thesis project in June, but the COVID-19 pandemic changed my plans. In the middle of August, I was happy to finally start with a very interesting project.

In my master’s thesis project, I am analyzing the genomic data of uterine leiomyomas. Uterine leiomyomas are benign smooth muscle tumors of the uterus. The prevalence is up to 70–80% in women. I am focusing on structural variants, such as translocations, inversions, insertions, huge deletions and amplifications. The HMGA2-RAD51B translocation is one of the best characterized structural variants in leiomyomas. This means that part of the chromosome 12 is attached to a part of the chromosome 14, so that HMGA2 receives active regulatory elements of RAD51B. This leads to a much higher expression of HMGA2 in tumor cells compared to normal cells. In addition to this well-known translocation, we have been lucky to come across and characterize some other structural variants in uterine leiomyomas.

Structural variants can be studied in many ways. Sometimes, if you have a hunch of the putative genes mutated and you are lucky enough, you might find something interesting by simply visualizing genomic data on IGV or some other visualizing software showing the alignment of paired-end data. There are also many bioinformatics tools which look for structural variants by utilizing algorithms. These tools, such as Delly, are analyzing discordant reads and split reads of the paired-end data. Also, bioinformatics tools analyzing read coverage can be used to detect copy number variations. Once you have found a structural variant, you may want to validate your finding. This can be done by using PCR and Sanger sequencing. These steps are exactly the ones that I am using for my master’s thesis project.

Circos plots are a nice tool for visualizing these structural variants. In the figure, you can see one of the preliminary Circos plots I have made by using RCircos (R package). Lines show translocations between chromosomes and intrachromosomal inversions, and the circular heatmap indicates copy number variations.

I have learned so many new things during the process, and the project is not even completed yet. For example, I have developed my skills in bioinformatics and learned about genetics and tumorigenesis of leiomyomas. I have also gained a better understanding of how research projects are performed and how technical difficulties can be approached and tackled. I am super lucky that I have had such great supervisors and colleagues, who I really want to thank. Also, I am very grateful for the support I have received from HiLife. It has been extremely valuable.

Vilja Jokinen

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DNA, comets and shaky hands

Hi everyone!

My name is Piia Karhu and I am a first-year student in The Master’s Programme in Human Nutrition and Food-Related Behaviour at the University of Helsinki. I received a HiLIFE scholarship for the summer 2020 to work in a research project of my interest. I completed my research internship at the Viikki Molecular Nutrition group. The group studies the molecular mechanisms by which diets, foods and diet-derived compounds mediate their effects on health and prevention of non-communicable diseases. I was very happy to join this group as molecular nutrition is a very fascinating field of science. Here you can read more about Viikki Molecular Nutrition group.

During my summer, I was privileged to take part in the study that examines the impact of dietary habits on faecal water genotoxicity.  In the study, colonial epithelial cells were exposed to feacal water. Feacal water was extracted from stool samples collected during dietary intervention with healthy volunteers and the DNA damage created by the faecal water was examined. Purpose was to study whether there are differences in DNA damage of the cells when exposed to fecal water from volunteers that followed either plant protein diet, animal protein diet or diet that contains half plant protein and half animal protein. We measured the DNA damage using single-cell gel electrophoresis known as Comet assay. It is a commonly used and straightforward method for measuring DNA strand breaks in cells. The term “comet” refers to the leaked-out DNA of the cell as it often resembles a comet. The more intensive the comet tail is relative to the head of the cell, the more the cell is damaged.

microscope image of green cell comets
Here is an example picture of the comets

I had very interesting and mind opening summer job as I have never worked in this kind of project before. I acquired valuable experience working in the lab, especially in the cell lab and learned how to culture and handle cells. Working in a cell lab was a very nice experience even though it took a while before my hands stopped shaking! During my summer I gained a lot of practical experience, which will boost my confidence working as a researcher in the future.

I want to thank my supervisor Anne-Maria Pajari for this opportunity to work in her research group and Hana Slabá for excellent guidance during the summer. Also, I am deeply grateful to HiLIFE for supporting me, this was a very valuable experience!