Posts

Posted on

Studying an unusual shrub (Eastern leatherwood) and the beginning of my HiLIFE grant

Lignin and its chemical properties are, for the most part, fully taken advantage of in most plant and tree species: it’s a molecule that occurs in the area between neighboring cells, inside the cell wall, and generally provides mechanical support and supports water transport. But this looks a little different in leatherwood, a small, understory shrub that lacks lignin in places where there are normally large amounts in other species, such as silver birch or Norway spruce. This allows its branches to bend well past what would easily break a spruce tree. Interestingly, we still do not understand why leatherwood evolved like this (other than the fact that being extremely bendy is obviously a fun skill).

Lignin, in this sense, can be thought of as one of the many Bermuda triangles of the plant world. While much of plant biology remains unknown, lignin is particularly interesting because how and why lignin is distributed, especially in leatherwood, remains a mystery.

My name is Dayla and, while I’m originally from Austin, Texas in the United States, I have lived in California, West Virginia, New York City, and now Helsinki. One of the reasons that I was drawn to the University of Helsinki is because of the access to plant science research, ranging from stomatal development to lignin formation.

Before entering the master’s program here, I was already considering whether a PhD in plant biology could be the right path for me, but I was scared. Was this really what I wanted? A decade of mass-murdering weeds for the sake of science?

The short answer, I think, is yes. The slightly longer answer is that I have been lucky enough to work with HiLIFE to spend four months exploring lignin and its many roles in leatherwood, poplar and Norway spruce. Over the course of this traineeship, I will have the opportunity to see how trees fit into the wider world of plant biology, learn new techniques (including how to pick up 20 micron thick pieces of wood using only a drop of water), and explore the possibility of a career in research.

In the past, I’ve worked with Arabidopsis roots to investigate genes responsible for growth and development. Now, with Kurt Fagerstedt’s group, I will have the opportunity to study a different facet of plant biology – what happens to a plant when one of its key macromolecules is modified.

However, the real main goal of this traineeship is to resolve the love–hate relationship that I have with lab refrigerators. They smell similar to how it feels to gag – that is to say, I gag every time I open one. Alas, this is where we store the true muscle of developing mutant plants, and the culprit of the smell: E. coli. This bacteria is partially responsible for the transformation of healthy, strong weeds, into sad, small plants that are no longer able to produce lignin properly.

Over the course of the next four months, I hope that I can either a) grow accustomed to the smell in the refrigerator or b) appreciate the importance of E. coli in plant molecular biology enough that it no longer bothers me.

Posted on

Field course in the tropical forests of Laos

Sabaidee! My name is Emmi Kaislasalmi, and I am a master´s student in forest ecology at the University of Helsinki. Earlier this year I got the HiLIFE Conference Grant to participate in a three-week intensive field course in Laos called “Tropical Forests and Agroforests”.

Here in this post, I am going to share my experience of the course. Please note that this course is conducted every second year (next time in January 2025), and you might have the chance to also get in if you want to learn more about tropical forests, the problems facing them, and the deep interconnection between forest well-being with societal and economic aspects.

Multicultural experience

The course was conducted by the University of Helsinki in partnership with a local university, Souphanouvong University from Luang Prabang. The course participants, students, and professors were from Finland, Laos, and Thailand.

We started from a UNESCO World Heritage City, Luang Prabang, where we got straight away immersed in the Lao culture as we arrived. Throughout the course, we learned about each other’s cultures and customs as we worked in groups of four, where the participants were at least from three different nationalities. Learning from one another was one of the greatest experiences for me.

On the second day, we headed to Nambak District, famous for its crispy river weed, “kaipen”, which is a delicacy we enjoyed throughout the course.

Pic. 1. Kaipen in making. The river weed is first harvested from the Nambak river floor, them processed, and left under the sun to dry. Usually, kaipen is topped with sesame seeds, tomatoes, and garlic, like in this picture, but other toppings can also be used. Finally, the kaipen is quickly deep fried before its ready to use. ©Field course: tropical forests and agroforests.

Hands-on approach and field research

After a short lecture and introduction on what we were about to do, we left to the field to conduct research. The research had two major parts, one was doing biodiversity research and forest inventory in the tropical forests and agroforests, and the other part was interviewing the locals and trying to understand their relationship with forest and forest products in terms of livelihood and food security in the Nambak District.

Pic. 2. Vieng Hinh Soung Village in Nambak District, one of the study villages in the field course. ©Dipjoy Chakma

In the forest, we learned to use different biodiversity and forest inventory methodologies, identify different tree and herbaceous species, find the indicators for forest disturbance, and how extremely diverse and beautiful the forests in Laos can be. We also learned that some trees make you itchy if you stand underneath them, some smell like cinnamon, and others bleed red sap, that looks like blood, if make a cut on the trunk.

By conducting the interviews, we learned about locals´ perceptions and needs when it comes to forests and forest products. Especially in the more remote villages, where access to stores and markets is not easy, people rely on non-timber forest products (NTFPs) such as bamboo, different wild vegetables and herbs, mushrooms, and bushmeat for sustenance and livelihoods. Firewood is also an everyday necessity for the locals, as cooking is done with using firewood. When building or renovating a house, the timber usually comes from the local community forests, which are cared and managed by the whole community.

What I left the course with

What I truly loved about the experience was that we did not only learn about the ecological and environmental aspects of tropical forests. Instead, the course had an interdisciplinary approach, and we learned about the social and economic realities that affect tropical forests, and how understanding and addressing these issues is key to sustainable forest and land-use management.

Looking ahead, I am convinced that we should have more courses and collaboration between disciplines and departments to address many of the current challenges regarding sustainable development and land-use. This approach is essential to bridge the divide between our current understanding of forests—focusing on their ecological and environmental dimensions—and the broader knowledge we should possess about societal, economic, governmental, and legislative aspects.

This interdisciplinary approach is needed to bring long-term solutions to the many problems facing tropical forests, including the loss of biodiversity, forest degradation, and deforestation. Moreover, it would also address the needs of the local communities and enhance their overall well-being.

Participating in this course was a truly enriching experience, and I am very grateful to HiLIFE for awarding me the HiLIFE Conference Grant since it made the experience accessible to me. My time in Laos was also very meaningful to me because I got insights about the direction in which I want to pursue my future career.

This field course in Laos was an unforgettable journey that deepened my appreciation for tropical forests and the critical importance of their preservation. The experiential learning, combined with theoretical insights and interactions with experts and local communities, enriched my understanding of ecology, research methodologies, and how the welfare of local communities plays a vital role in ensuring the health and prosperity of forests.

Posted on

My first-ever academic conference experience in Tromsø, Norway

Hi all! My name is Aliisa Niemelä and I am a freshly graduated M.Sc. (Pharm), also known as proviisori, from the University of Helsinki. I was delighted to receive a HiLIFE Conference Grant to participate in my first-ever academic conference in June 2023. I am here to tell you about my experience!

Tromsø, located in the beautiful Northern Norway above the Arctic Circle, is a scenic and historical city surrounded by the sea, fells and mountains. The scenery was breath-taking and unlike anything I’d ever seen before! I was thrilled.

The scenic view outside Tromsø Airport.

Did you know that Tromsø is often referred to as “Paris of the North”? This nickname speaks for itself – the city has a lively, historical and sophisticated atmosphere. But more importantly for us, the city is home to the world’s northernmost university, University of Tromsø – The Arctic University of Norway. UiT is the only university in Norway to offer both three-year bachelor and two-year master programmes in Pharmacy, which are compliant with the Bologna Process.

7th – 9th of June 2023 UiT and the Department of Pharmacy hosted the 10th Nordic Social Pharmacy Conference (NSPC), a three-day event focusing on “Pharmacist services of tomorrow”. The Nordic Social Pharmacy Conference 2023 brought together researchers and practitioners from Nordic countries and all around the world, even all the way from the US. We discussed and learned about key topics concerning social pharmacy, pharmacy practice and pharmacoepidemiology. In my studies I have focused specifically on social and clinical pharmacy, so NSPC 2023 was an excellent event to deepen my knowledge and to network internationally in my field. The conference included plenary sessions, workshops, poster sessions, oral presentations and pre-conference master classes and was all about sharing experiences and ideas and learning from each other.

The conference had the warmest atmosphere and I felt so welcome to my first-ever conference. And it wasn’t all about sitting in auditoriums – we also enjoyed the nature while climbing up Sherpatrappa (1200 stairs) to Storsteinen mountain 421 meters above sea level. This might have been the most challenging part of the trip! 😀

View from Strosteinen after hiking up Sherpatrappa.

The highlight of the conference for me was getting the opportunity to share the findings of our own research and present our poster entitled “Developing clinical pharmacy expertise with a postgraduate pharmacy programme: Individual interviews with specializing pharmacists and their line-managers” in one of the poster sessions of the conference. This was a great experience for me and I am grateful for all the discussions around this topic.

I will cherish this experience for years to come and look forward to my next scientific conference! I want to thank my dear colleague Raisa Laaksonen, University of Helsinki and HiLIFE for the experience and support received!

Posted on

Meet the Aalto-Helsinki iGEM team 2023!

We are the Aalto-Helsinki iGEM team 2023!

We are a very diverse group of 10 students and here you can find about us and our project.

What is iGEM?

Welcome to the exciting world of synthetic biology! At the forefront of this rapidly developing interdisciplinary field is the International Genetically Engineered Machine (iGEM) competition, which originated from the prestigious Massachusetts Institute of Technology (MIT) in Boston, USA. Synthetic biology has enormous potential applications in fields such as medicine, food, agriculture, and energy. iGEM challenges students from around the world to design and implement innovative projects using experimental work, modelling applications, and cutting-edge design techniques, all within a short time frame. To learn more, please visit the official website: https://igem.org/

What is our idea?

Our team was born in February 2023, and shortly thereafter, we initiated our ideation process. Discovering a problem to address in our common interest proved more challenging than expected. Following intense ideation sessions, we came up with two proposals, which we subsequently presented to several experts. Consequently, the team reached a consensus to merge these ideas and address two pressing global challenges: plastic waste, and food scarcity.

The scale of plastic waste pollution is alarming, with over 350 million tons of plastics manufactured annually, and over 70% of plastic waste accumulating in landfills and oceans. This poses a significant environmental threat to ecosystems, marine life, and human health. Without any further changes to current policies, global plastic waste generation is projected to triple to one billion metric tons by 2060. Currently, the goal of plastic recycling is to reduce the need for primary plastic production. The competition between virgin plastics market and recycled plastics make recycling less attractive, since newly produced plastic has a higher relative material efficiency due to the ongoing availability of lower-cost feedstock.

Simultaneously, global food security remains a pressing concern, with over 820 million people undernourished and the need to increase food production by 70% before 2050. Conventional methods are insufficient to meet this growing demand. Focusing on the nordic countries, most of the agricultural activity focuses on meat production, even though it is a well known fact that it has a huge carbon footprint, and takes up double the resources than plant based food production. As the demand for food protein continues to rise, the development of novel and sustainable protein sources becomes environmentally and economically significant. There is great potential for producing protein-rich feed or food additives in the form of algae, yeasts, fungi and plain bacterial cellular biomass. They have a lower environmental footprint compared with other plant or animal-based alternatives.

We are focused on a circular economy system, aiming to reduce waste and utilise resources more efficiently by converting waste into valuable proteins. Our objective is to develop an optimised enzymatic plastic depolymerization system and demonstrate the feasibility of protein production utilising polyethylene terephthalate (PET) as the primary source.

Our project, PET-2-Protein, aims to develop a proof-of-concept approach for converting PET into proteins. Naturally occurring PETase enzymes are able to break down PET plastics into monomers such as terephthalic acid (TPA) and ethylene glycol (EG). Enzymatic degradation of plastic waste is an eco-friendly alternative to chemical plastic recycling. Our research aims to address the fundamental issue of plastic waste by focusing on plastic reduction. Consequently, we do not only design an optimised system for producing plastic-degrading enzymes but also optimise the enzymatic depolymerization of PET into TPA and EG, and finally, the microbial conversion of those monomers into proteins.

More about iGEM

iGEM is not only about designing our project. Using synthetic biology to address real-world problems requires thoughtful engagement with the world. In iGEM, this is referred to as Human Practices: thinking deeply and creatively about whether a synthetic biology project is responsible and good for the world. Throughout our project design we have contacted various experts and companies whose expertise shared similarities with PET-2-Protein, who have helped us to refine protocols and objectives. We have discussed several matters such as practicalities related to our methodology, the different uses that our end product could have and the ethical implications related to our work. Moreover, we are also focused in community outreach and science communication, addressing different audiences so that they can get to know our project, synthetic biology and iGEM. Our team is preparing a “science for children” workshop in Heureka as well as a collaboration with The Science Basement.

If you are interested in knowing more about our project and journey, you can visit our webpage, social media and blog.

Thank you for reading!

Our team wants to thank HiLIFE and the University of Helsinki for supporting the iGEM team and its project. Their support has been essential for us in order to participate in the iGEM program and competition. It has been an amazing experience and opportunity for all of us so far!

Posted on

Where passion meets purpose

Hi fellow students!

My name is Aina Rossinyol Fernàndez, and I am a second-year master’s student in the Ecology and Evolutionary Biology Programme here at the University of Helsinki. I am passionate about understanding and preserving the biodiversity of our planet, and I chose this master’s programme to deepen my knowledge of applied biodiversity conservation.

In March 2023, I attended the Student Conference in Conservation Science (SCCS) that took place in Cambridge, UK. SCCS is the only international series of conservation conferences entirely aimed at students. In case it is of your interest, SCCS is yearly conducted in Cambridge (UK), Brisbane (Australia), Beijing (China), Bangalore (India), New York (USA) and Budapest (Hungary).

The conference spanned three days and offered both in-person and online attendance options. Thanks to the HiLIFE Conference Grant, I had the great opportunity of participating in person. As the conference started early on the 28th of March, I decided to get to Cambridge on the 27th. I spent the whole morning exploring the city’s stunning architecture and streets as well as the river Cam. One of the things that surprised me the most was finding colleges all over around (Cambridge has a total of 31 colleges!). My favourite one was Christ’s College, as it is the one Charles Darwin stayed at. In the afternoon, I ended up joining a tour of 11 Indian people – including the guide – about the linkages in the history of Cambridge and India. Even though I was the only non-Indian participant and felt a bit lost in some of the explanations, it was such an interesting tour. This city has so much history to tell!

The conference days were very intense, but I was ready to absorb knowledge like a sponge! The conference included many interesting planetary talks, student oral presentations and poster presentations, as well as activities to facilitate networking and to introduce numerous both national and international institutions and organisations involved in conservation. I was truly admired by the wide range of incredible conservation work being done worldwide! Some of the vast array of topics covered included species distribution in the Anthropocene, human-wildlife conflict, ecosystem services in a changing world and people’s perceptions of nature.

The conference counted with an exciting programme of workshops. I wish I could have attended all of them, as they all seemed very interesting. However, we could just attend two of them. On the first conference day I attended the “Collections-based research” workshop. After discussing the diverse ways that collections can be used in biological research, we had a behind-the-scenes tour of the zoological collections housed in the University Museum of Zoology in Cambridge. The collections harbour over two million zoological specimens. Yes, over two million! The specimens are kept in storerooms at a constant temperature and humidity to avoid pests, such as beetles and moths, as well as to prevent mould formation. And now you may be wondering “Why do they put that much effort in store and catalogue this huge zoological collection?” The answer is easy. All these specimens collected over the past 200 years are a precious record of life on Earth and significantly contribute to scientific knowledge. For example, collections can provide essential data about animal distribution in an ever-changing world. Thousands of researchers from different disciplines from all over the world come along to study the collections to better understand and appreciate our natural world.

I especially enjoyed seeing specimens collected by Darwin. I would have literally spent days exploring these never-ending collections!

Fundraising is essential for conservation projects and thought that having the opportunity to meet face-to-face a donor would be a great opportunity to develop relevant skills on grant applications. That is why on the second day of the conference I attended the workshop entitled “Tips and tricks for writing grant applications: the view from a funder” held by Claire McNulty, the executive director of the National Geographic Society of Europe and the Middle East (Western Asia). For those who don’t know National Geographic Society, it awards grants to people working on conservation projects all over the world. Claire gave us practical and very useful tips, which can also be used in other funding sources, on how to develop a successful grant proposal.

As a young and aspiring conservationist, I believe that the best way to start my professional career is by learning from experienced tutors and experts in tropical conservation as well as from fellow like-minded students. Throughout the conference, I had the opportunity to interact with many enthusiastic students and renowned researchers and professors from all over the world. Speaking about projects, career paths and future plans, while exchanging ideas, was very inspiring to me, and I have no doubt that it will be valuable for my conservation journey. Additionally, getting to know conservation perspectives and practices from cultures all over the world allowed me to become more open-minded.

After those three very inspiring days, which combined learning, forging lifelong connections and overall unforgettable experiences, I can assure you that I left the conference with even more willingness to make a positive impact on tropical conservation.

In-person participants of SCCS 2023

The love for all living creatures is the most noble attribute of man – Charles Darwin

Even though this time I just attended, I can’t wait to present my own work in future SCCS conferences… who knows where! I am very grateful to HiLIFE for awarding me the HiLIFE Trainee Conference Grant and to SCCS Cambridge for organizing such an inspiring conference.

Thanks for reading me!

Aina Rossinyol

Posted on

Whether or not obesity pandemic is stopped will define public health globally in the near future

Laitinen seeks to understand hunger-satiety signalling to understand its root causes.

Check the introduction video where she describes her project.

Suvi Laitinen, 21, researcher and MD-PhD-student from the University of Helsinki started meticulously chasing her hypothesis about elevated hunger/decreased satiety in the human brain in 2022. She co-founded the Obesity Curiosity research project with Dr Teemu Aitta-Aho (PI of the Loss of Control Behaviour lab, Department of Pharmacology, University of Helsinki). She explains the big idea behind Obesity Curiosity:

“It seems that this effect [of environmental factor(s)] causes us to eat a tiny bit more every day. I hypothesise people have decreased satiety, increased hunger, or both. Some people seem to be more vulnerable to the effect while others are more resilient. This would explain why weight management is gruelling. The urge to eat is one of the most powerful signals of the body and almost impossible to resist.”

Laitinen’s PhD project is part of Obesity Curiosity and her goal in the first stage, is to develop a human arcuate nucleus model. Then in the second stage, they will use the model to study the effect of factors of interest, such as medications with weight gain as a side effect, on the human brain in vitro.

Currently, Laitinen is completing her research at a scientific collaboration visit in Dr Florian Merkle’s lab at the Institute of Metabolic Science University of Cambridge, funded by the Helsinki Institute of Life Science (HiLIFE) Undergraduate Student Research Trainee Scholarship. “My work here is focused on directed differentiation of human induced pluripotent stem cells (hiPSC) to hypothalamic neural origin cells, including neurons. This way we can generate a model that quite faithfully replicates human physiology without having to deal with the inaccessibility of the human brain otherwise. The hiPSC cells have been generated from volunteer donations of patients in past”, she explains.

“Working in Dr Merkle’s lab allows me to learn their robust methodology of hiPSC-derived 2D hypothalamic cell culture and with his generous support I am highly grateful of, I have expanded into preliminary testing of my own protocol to generate organoids. I hope to be able to establish corresponding cultures when I return to Helsinki. The research methods learnt during the exchange will be the firm foundation of my PhD research project, and forming strong collaboration will be immensely helpful. I am highly enthusiastic about this opportunity!”

Laitinen independently designed her new research opening involving a novel methodology of assembloids based on the literature of the field in 2022 and convinced Dr Aitta-Aho to become her supervising Principal Investigator in October of the same year. She has since executed her research in the Loss of Control Behaviour lab of Dr Aitta-Aho alongside her medical school studies at the University of Helsinki. Obesity Curiosity, the wider project involving multiple approaches to study the root causes of the obesity pandemic is their joint effort.

“To understand obesity, I have started the same way as many scientists before me, by finding special cases and trying to understand the general rule from there. Common clinical knowledge and scientifically proven fact is that many psychiatric drugs statistically cause patients to gain substantial amounts of weight in a relatively short period of time. I want to study this with a novel human brain model. Long-term, I hope to be able to help in improving the treatment and prevention of obesity”

Before founding Obesity Curiosity, Laitinen had close to nine months of full-time biomedical research experience. After winning Millenium Youth Prize 2018 , she worked at Aalto University in the Department of Neuroscience and biomedical engineering rotating between different laboratories in summer 2019, exploring what the work of a researcher is like. Summer of 2020 and the four months between final exams and starting medical school in 2021, she worked at Professor Pekka Katajisto’s lab (HiLIFE Institute, University of Helsinki) in stem cell research.

In Katajisto lab, Laitinen investigated basal mammary gland cell adhesions to EMC proteins in the normal development and the cancer of mammary gland epithelium.

“The experience was amazing! Professor Pekka Katajisto and Dr Johanna Englund, my supervising researcher in the lab, always believed the most and best of me, teaching me to reach my full potential and ask all my questions. They also demonstrated how great supervising at best can be!”

Her work in 2021 also resulted in her first two co-authored publications, an accomplishment she is proud of and grateful for. “In the scientific world, they are proof that I am capable of executing research at the meticulous level, and maybe help to get respected as a fellow researcher regardless of my young age”

In her first year of medical school, she got accepted to the MD-PhD-program at the University of Helsinki, which had been her goal ever since she learnt that it is possible to become physician-doctor. “It was a nerve-wracking process, as one can apply for the program only once [in the first year of medical school] and I had focused my work towards that goal for a long time. Acceptance felt like reaching the top of a mountain – a completion – and a wonderful landscape of the research world opening in front of me!”

Her initial interest in cancer led to her choosing the first rotation lab studying ovarian cancer. She completed 2 months rotation in the Dr Anniina Färkkilä’s lab (Systems Oncology Research Program (ONCOSYS), University of Helsinki) in the summer of 2022 to learn about three cutting-edge methodologies: cyclic immunofluorescence method, patient-donated sample-derived organoids and complex cell typing flow cytometry.“The point of rotation is to get experience that helps with PhD projects, and I strongly believe these methods will help me design my own project and readouts to investigate my research questions”

“The burning question keeping me up at night is What causes the obesity pandemic? Ultimately this is about the health of over 700 million people suffering from obesity already today and countless others to come. Obesity affects everyone, if not directly themselves, their loved ones. I have a hypothesis, so I am trying my best to test it. I am working in molecular neuroscience to hopefully make the world a better place.”

Laitinen was awarded HiLIFE Undergraduate Student Research Trainee Scholarship for international research exchange in November 2022. She secured a position in Dr Merkle’s lab to conduct the research visit between May-August 2023 working on her Obesity Curiosity project.

Posted on

European Society of Human Genetics conference 2023

Hi, we are Rafaela, Victoria, and Johanna, and we are all recipients of the HiLIFE conference grant. In June, we travelled to Glasgow, UK to attend the European Society of Human Genetics conference. 

From right to left: Johanna, Victoria, Rafaela, and Maria Francesca, a visiting scientist and medical doctor in our group.

We are all students of Marco Savarese’s lab (Folkhälsan Research Center) studying genotype-phenotype correlations in rare inherited muscle diseases. Thus, ESHG was a great opportunity for us to learn about the newest, most cutting-edge research in genetics, and to start building connections in the field. 

This was the first international scientific conference experience for all of us, and thus it was an extremely valuable opportunity to gain professional experience in networking, poster presenting, and scientific discussion, early on in our careers. 

The conference offered special opportunities for newer members of the human genetics community, including events organized by ESHG Young Geneticist Committee (ESHG-Y). As first-time attendees, their events and workshops felt extremely helpful and informative and provided excellent opportunities to connect with our peers.  

Overall, human genetics is a broad topic, which was reflected in the wide variety of research topics covered at the conference. Some of the reoccurring topics included AI-based solutions for variant interpretation, variant classification methods, and multiomics applications in genetics research. We wanted to highlight a few topics that we found most interesting and relevant in our work with rare genetic muscular diseases.  

Artificial intelligence-based solutions in human genetics 

Implementing AI based solutions is a hot topic in genetics, and many of the conference presentations reflected this excitement. Among the most interesting ones were a talk about the Eye2gene project and a poster about the Gestaltmatcher database.  

The Eye2gene project was inspired by clinicians diagnosing inherited retinal disease from eye scans. The disease causes specific patterns of damage to the eye. For the clinicians, it takes years of experience to be able to recognize these patterns. Thus, there are few doctors capable of reaching such diagnosis, causing delays in patient care. The Eye2gene method uses AI to interpret these eye scans, and the results show reliable performance. This method could not only speed up diagnosis but also reduce human error and variability of analysis from clinician to clinician, making the diagnosis more precise. 

In relation to our work with rare muscular diseases, the Eye2gene project is a great example of how improved understanding of the phenotype can aid with understanding the genetic background of the diseases as well. Although this approach would probably be much more difficult to implement in MRI imaging used in muscular diseases, it is an intriguing potential future application.   

The Gestaltmatcher is a similar AI-based approach to medical imaging analysis. This database allows an authorized user to upload medical images associated with rare diseases. The AI of the database groups similar images together to find groups of patients with common phenotypes. A major challenge in rare genetic diseases is often the small number of patients. Thus, it is extremely valuable to be able to share data and to gather a database as large as possible from the limited number of patients with a similar phenotype. Larger databases allow for better understanding of the disease phenotype and the genetic background of the disease, and ultimately, to develop treatments for even the rarest of genetic diseases. 

Gestaltmatcher showed that AI has an enormous potential in assisting clinicians and researchers in pattern detection in patient cohorts. This is an asset we should consider taking advantage of in our group’s muscle disease patient cohorts to better understand genotype-phenotype relationships in these diseases. 

Improved sequencing methods and multiomics approaches 

Multiomics approaches were a reoccurring topic at ESHG and it was featured in several presentations and posters throughout the event. In the context of genetics, the term multiomics generally refers to the practice of combining genomics, transcriptomics, proteomics, and sometimes epigenomics. Multiomics has many applications: it can be used for interpretation of variant pathogenicity or to uncover novel disease-causing variants, for example. A presentation at the conference revealed a method of combining genome sequencing with proteomics data to help uncover novel causative variants or reach a final classification for variants of uncertain significance. Epigenomic and transcriptomic approaches were also featured.   

The use of newer, more advanced sequencing approaches, such as long-read sequencing, is also growing rapidly, with regards to both DNA and RNA. In particular, targeted long-read sequencing is being used to diagnose specific diseases since it includes only genes that have a known association with a disease, making it cheaper than whole genome long-read sequencing, but more accurate and precise than traditional gene panels.  

The presentations at the conference clearly emphasized the advantages of multiomics approaches and new sequencing methods. Clearly, these are growing topics in human genetics, and thus, it was useful to hear stories of how these methods have been implemented in practice. This helps us to start developing an understanding of how these methods could be most effectively implemented in the context of muscular diseases.  

The conference venue, Scottish Event Campus (SEC) in Glasgow, Scotland.

This conference experience allowed us to learn about many new topics and to broaden our understanding of human genetics. It was inspiring to hear about the outstanding research and the future of genetics. This trip left us inspired and even more excited and motivated to continue working on our projects with newly developed skills, knowledge, and connections. On top of that, we had a wonderful time together in sunny Glasgow. 

We would like to thank HiLIFE for making this trip possible! 

Posted on

Granting a Drug an ID Badge – Harnessing Receptor-Mediated Transcytosis for Crossing the Blood Brain Barrier

Imagine an agency headquarters with tight security policies in place. There are security guards on all doors and no entry without an ID badge. Various employees pass by the gate, all with different job titles and responsibilities. Entrance is also granted for the supportive personnel such as maintenance, cleaning services, and catering. Everybody knows their own specialized role and together with a strong management it is made sure that everything flows in a highly organized manner. Occasionally, an intruder tries to invade the establishment, but they are swiftly stopped by the security and police officers who arrive just a moment later to make sure nothing was stolen, and no one harmed. And if something or someone was to be injured, a team of healthcare professionals would arrive to take care of the situation.

In a similar way, in our bodies, molecules are travelling in the bloodstream and when wishing to enter the brain they arrive to the gate of the blood-brain barrier, or shorter the BBB. During my HiLIFE Research Trainee internship, I got an opportunity to join the Brain Targeting Program at the Wyss Institute for Biologically Inspired Engineering at Harvard University. Research in this translational program centers around the study of the BBB.

What is the Blood-Brain Barrier?

The BBB is a highly specialized structure consisting of endothelial cells that form the blood vessel wall or lumen. These cells are located very close to one another as they form the so-called tight and adherens junctions by binding to multiple proteins. This compact structure allows a limited number of molecules to pass through the BBB. Molecules can pass through via diffusion only if they are small enough or lipid soluble. Another mechanism to cross the BBB is by utilizing transport molecules which carry some substances from the blood to the brain parenchyma (that is, the functional tissue of the brain). Thus, only if the molecule has a correct ID badge, it can enter to the brain.

In the BBB, on the brain side, endothelial cells are enclosed by other cell types: pericytes and the end-feet of astrocytes that support the integrity of the barrier – similar to those security guards in the agency headquarters. To protect the brain from the occasional invasion of intruders, there are microglial cells which work with astrocytes to engulf unwanted molecules or injured cells, and produce cytokines which amplify inflammatory signals to increase the body’s response to the intruder. There is also an efflux mechanism that can expel the uninvited guests who manage to slip through the BBB. Not only do astrocytes contribute to the integrity of the BBB, but they also connect neurons to the vasculature. Thus, there is dynamic communication between the blood vessels and the brain to keep the entire structure highly functional – in our agency example they function like a network of guards with their security earpieces.

Together, the BBB with all the different cell types form the neurovascular unit. This specialized structure is distinct from any other blood vessels in the body, and it therefore also functions very uniquely. It maintains the regulation of blood, oxygen and nutrient flow, immune response, and waste clearance which are all crucial for the homeostasis – the self-regulated normal functioning – of the brain and the body.

Image representing blood vessel surrounded by pericyte and astrocyte cells. On the brain parenchyma side neurons and microglia.
Schematic view of the blood-brain barrier. Created with BioRender.com.

The Challenge for Delivery of Therapeutics into the Brain

As much as the BBB protects the brain from unwanted guests such as microbes and toxins, it also very effectively inhibits various drug molecules from reaching the brain. The entry of up to 98% of small-molecule drugs and 100% of larger macromolecular therapeutics is blocked by the BBB. This makes it difficult to treat different diseases affecting the central nervous system, such as neurodevelopmental and neurodegenerative diseases or brain tumors.

Various methods for enhancing brain drug delivery have been developed over decades, yet only a few have proven effective. Some of these technologies need surgery or other invasive methods such as deep brain stimulation, while others such as receptor-mediated, nanoparticle carrier, or focused ultrasound strategies are non-invasive. Our Brain Targeting Team at the Wyss Institute focuses on target discovery and validation utilizing the non-invasive receptor-mediated method, named as receptor-mediated transcytosis, for more efficient brain drug delivery. My main tasks involve handling human brain tissue samples and analyzing both transcriptomic and proteomic data to identify and assess the transport potential of numerous targets.

Receptor-mediated transporters are endogenous proteins located at the BBB blood vessel wall that can have various functions in the body. For example, the most studied receptor-mediated transporter, the transferrin receptor, normally functions in iron uptake from the cell membrane inside the cell. Antibodies can be engineered to bind to these receptors in a way that also other molecules than only the endogenous ones can be internalized. Antibodies linked with desirable therapeutics and designed to utilize these transporter targets are often referred to as Trojan horses, as they are only allowed to cross the BBB when in disguise, subsequently exerting their therapeutic effects once inside the brain. Thus, transferrin receptors can recognize an antibody while inadvertently allowing the entire complex to be carried in the brain without the body’s surveillance system recognizing the foreign drug molecule.

Blood vessel on the bottom on the image, lined by endothelial cells. On top pericytes that are enclosed by astrocyte end-feet. Drug from the blood vessel is carried across the blood-brain barrier with a receptor protein.
Schematic view of the receptor-mediated transcytosis for drug delivery across the blood-brain barrier. Created with BioRender.com.

I prefer to imagine that the BBB and therapeutic compounds are on the same side of the battle. Thus, instead of a Trojan horse, this technology harnesses the capabilities of our body so that the BBB offers a helping hand in drug delivery and welcomes an additional aid to battle against protein aggregates found from neurodegenerative diseases or tumor cells in brain cancers when our body and its cells need assistance. Ultimately, it is about granting an ID badge for the drug, for the invited guest in the headquarters of our wondrous body.

A little bit about me:

I am a Master’s student in Translational Medicine at University of Helsinki, currently located in Boston, United States, to conduct a six-month-long internship at the Wyss Institute at Harvard University. In my M.Sc. studies I specialize in translational neuroscience and personalized medicine. My Master’s thesis looked into the molecular mechanisms behind Alzheimer’s disease and while in the midst of my experiments, I got enchanted about the BBB. Therefore, I am deeply thankful and excited to contribute to the Brain Targeting Program at the Wyss where innovations are translated into clinical practice. My next HiLIFE Trainee blog post will provide more insights into my internship experiences, so stay engaged for more!

Mareena Hyypiä

Posted on

Practicing networking at the Lake Conference

My name is Reetta Ojala, and I am finishing my Master´s studies in neuroscience at the University of Helsinki. I am interested in decision making and I was very fortunate to be able to write my thesis in Nelson Totah’s lab. My thesis was about beta oscillations’ role in stopping a movement. Nelson suggested that me and my colleagues working on the same topic would go to the ‘Lake Conference: Sensation and action’ in Switzerland to present our results in poster form. We applied and got accepted and then as a cherry on top, I also got the HiLIFE Trainee conference grant to support my journey. I was very excited to hear interesting talks about this topic, but at the same time, I was very nervous about the mixing and mingling part of the conference. I would want to make connections, but I am very shy to start conversations. I was also terrified of presenting my poster. I decided to take this trip as a  practice to improve my social and presentation skills.

The location by the Lake Thun was beautiful.

We arrived in Thun a day before the scientific program started, so we had some time to adjust and to see the surroundings a bit. This turned out to be a good decision, as the conference days were long and tiring, because there were so many interesting topics; transformation of sensory evidence into action, what role do emotions have between sensation and action, large-scale neuronal computations and much more.

At first, I felt overwhelmed in the middle of all the socializing action. Luckily, I was not there alone, and my colleague dragged me to meet other people. We are both starting our PhD projects in the same lab soon and we got to know other PhD students that are a little further in their studies. I ended up having very vivid conversation with one young woman about animal research ethics, which is very close to my heart. In the end I exchanged contact information with quite a few other students too.

Me and my colleague Joana Doutel Figueira

In the last evening, it was time to face my biggest fear, the poster presentation. It started in the worst possible way. A big name in the field came to hear me. I felt my cheeks turn red and I started to stammer. I took a deep breath, gathered myself and started talking more slowly. A little voice in the back of my brain was shouting that this person knows so much more than me; how should I present all this? But I remembered my PI’s words. This is my work, and I am the expert on it. So, I just explained everything, some parts of the analysis more briefly. I think the professor saw my struggle. He was very friendly and made some very good questions and gave constructive feedback. We talked for a while and after he left, I wrote down the comments to go through them later. After that it was much easier to present to the other students.

I am very happy that I had this opportunity. And I am proud of myself for overcoming my fears and talking to people. I got new ideas for my project and new perspectives on this area of research. The scientific talks and the conversations with others made me feel that I am on the right path in my life. I want to encourage all the students to apply to conferences! The information load will be heavy, but the point is not to take every talk as a lecture. It is more about getting inspiration and making connections, meeting other people who are interested in the same things that you are. I surprised myself positively, but there is still much to learn. Maybe next time I dare to go to talk to the PI whose talk I found totally fascinating.

Reetta Ojala

Posted on

From A Nearby Ditch to Lab Bench: Exploring the Soil Viriome

 

Hello! My name is Erika Nordman, and I am a second-year student in the Bachelor program of Molecular Biosciences at the University of Helsinki. I am thrilled to be one of the 2023 HiLIFE Research trainees and during my internship, I am working on characterising a novel soil bacteriophage.

When I started my studies in University of Helsinki in autumn 2021, I quickly discovered my interest in the micro-world, particularly in bacteriophages. Bacteriophages are viruses utilising the bacterium’s machinery to replicate and spread. What initially caught my attention about bacteriophages was their funky appearance and as I delved deeper into the fascinating world of bacteriophages, I surprised myself how intriguing these alien-like creatures truly are!

 

I started my traineeship last April under the lead of Minna Poranen and Hanna Oksanen at the Viikki campus in University of Helsinki. The group is involved in numerous research projects focused on studying viruses, and I feel honoured to have my own project within their group. So far, my internship has been very exciting for me, as becoming a virologist and scientist is my ultimate career goal in the future. Being able to participate in a research project within my own field of interest is a valuable opportunity to get during the early stage of my studies.

Applying Skills from a Lab Course in Research Work

Last autumn, I enrolled in a Helsinki University course “Practical Exercises of Bacteriology and Virology”. During our lab course, we collected a soil sample from the Viikki campus, enriched the sample and performed plaque assay using Bacillus cereus as the host bacterium for our experiment. The phage isolate was grown and purified by rate-zonal gradient ultracentrifugation and morphology of the bacteriophage was observed through transmission electron microscopy (TEM) and negative staining, and we determined the sizes of the main virion proteins using SDS-PAGE.

Our virus was assigned the name BCIP-1 (short for B. cereus infecting phage). BCIP-1 was found to have an icosahedral  structure and possibly contain a lipid-layer inside the capsid head. In the image below are our transmission electron microscopy pictures of BCIP-1 virions obtained from our laboratory course. Unfortunately, the virus capsid appears empty, suggesting that something in our purification protocol used during our lab course caused the loss of BCIP-1 genome and potential fragmentation of the virus’ head and its possible tail.

Since the main objective of the lab course was to learn the basic protocols in virology, there was limited time for troubleshooting and repeating the experiments. My traineeship goal is to optimise the conditions for successful virus purification, redo the transmission electron microscopy and conduct additional experiments to uncover other properties of BCIP-1. For example, I would like to verify the presence of the lipid layer inside the virion, determine whether the BCIP-1 genome consists of DNA or RNA and if the genome is circulated or linear.

Negative-stained transmission electron microscopy pictures of the icosahedral BCIP-1 virions from University of Helsinki lab course “Practical Exercises of Bacteriology and Virology” in autumn 2022.

The Power of Laboratory Courses in Virology Discoveries

A similar laboratory course was enrolled at the University of Jyväskylä in 2010, where a bacteriophage isolation from a boreal lake water sample led to the characterization of a new type of virus in the family Finnlakeviridae. The described virus is unique as it is currently the only known icosahedral internal membrane-containing virus containing a single-stranded DNA genome (Laanto et a., 2017).

The B. cereus bacteriophage that I have isolated has similar properties with the Finnlakeviridae representative virus called FliP (Flavobacterium-infecting phage). These characteristics include isolation from a boreal environment, icosahedral capsid morphology, and an inner lipid membrane. However, this virus infects a gram-positive bacterium while the host of FLiP is gram-negative. The similarities make my virus extremely intriguing, since they suggest a possibility that BCIP-1 could be evolutionarily close to FliP.

 

Light scattering zones indicate the migration of the virus in a sucrose gradient during rate-zonal virus purification. These zones are documented and collected, and the protein concentration of the purified virus is determined using the Bradford assay.

Unravelling the mystery:  Piece by Piece

So far, my journey with this virus has been filled with trials and errors. Since this bacteriophage has never been studied before, information is gathered bit by bit, combining and comparing various factors that could influence its ability to infect its host.

Currently I am concentrating on establishing buffering conditions to preserve the virions’ integrity and infectivity during virus purification. Once successful, I will have the opportunity to redo transmission electron microscopy and hopefully observe some intact virus particles! Ultimately, by comparing the characteristics identified with FLiP, my aim is to assess the potential of BCIP-1 being evolutionarily close to it and determine the possibility that BCIP-1 could belong to the same viral family.

Making novel viral discoveries is crucial, due to the immense number of viruses present in the environment, with only a fraction having been studied thus far. Viruses exhibit a vast genetic diversity within the soil, influencing the ecological dynamics in their respective ecosystems. Bacteriophages play a significant role in the horizontal gene transfer among their host organisms, maintaining the microbial homeostasis and contributing to nutrient circulation and organic matter decomposition. (Batinovic et al. 2019) By studying new viruses, we can enhance the understanding of the dynamics between viruses and their hosts, unraveling the mechanisms of viral infection, replication, and spread. Bacteriophages have wide-ranging applications in research and many biotechnological methods, and making novel viral discoveries fuels advancements in biotechnology, medicine, and bioremediation.

Everything Big Starts with Something Little

It has already been an extraordinary experience at this stage of my studies to witness how scientific projects can emerge from seemingly insignificant beginnings, such as collecting a spoonful of soil from a nearby ditch for a laboratory course. Step by step the puzzle of this bacteriophage is unraveled, and I have the privilege of being the first one to make discoveries about this virus. I am very curious to witness the pieces slowly come together enabling me a deeper understanding of this virus. Who knows, perhaps this virus is truly one-of-a-kind. I am looking forward to providing you with updates on my project in my upcoming HiLIFE blog post!

References:

Batinovic S, Wassef F, Knowler S, Rice D, Stanton C, Rose J, Tucci J, Nittami T, Vinh A, Drummond G, Sobey C, Chan HT, Seviour R, Petrovski S, & Franks A. 2019. Bacteriophages in Natural and Artificial Environments. Pathogens, 8(3), 100. https://doi.org/10.3390/pathogens8030100

Laanto E, Mäntynen S, De Colibus L, Marjakangas J, Gillum A, Stuart DI, Ravantti JJ, Huiskonen JT, Sundberg LR. 2017. Virus found in a boreal lake links ssDNA and dsDNA viruses. Proc Natl Acad Sci U S A. 114(31):8378-8383