From the Hub of Thousand Lakes to the World’s Leading Biotech Hub

“Everything is bigger there, one needs a car to get anywhere, the baseball and football they play are something else, and it is supposedly the college town and biotechnology hub.” This was the rather stereotypical view of Boston I had seen and heard from multiple sources (such as many American movies) before crossing the Atlantic for the first time and landing to one of the oldest cities in the United States. For the next six months, I was going to work as a HiLIFE Visiting Graduate Researcher at the Wyss Institute for Biologically Inspired Engineering at Harvard University.

The Wyss Institute has a strong emphasis on translating bioinspired innovations and research findings into clinical use. The number of patents, licenses and start-ups deriving from the Wyss is astonishing: during the 14 years of the institute’s existence, over 4000 patents have been filed and 56 start-ups founded. To enable this technology translation, Wyss operates through extensive collaboration with industry, government, foundations, and philanthropists. The Wyss teams have experts from different fields ranging from engineering to veterinary medicine, from general medicine to bioinformatics, and from molecular biology to bioethics.

The original six months got extended and therefore, during the past eight months, I got the opportunity to work in Donald Ingber’s (M.D., Ph.D.) lab in the Brain Targeting Program at the Wyss. Of these months, six I was present in Boston and the final two contributing to the program remotely from Finland. The Brain Targeting Program aims at discovering and developing new brain transport shuttles and brain-targeted therapies to more efficiently treat diseases in the central nervous system, such as neurodegenerative diseases and brain tumors. For reading more about the research topic, please have a look at my first blog post. The internship was certainly the most remarkable experience during my Translational Medicine Master’s studies at the University of Helsinki, and I could have not imagined a better way to complete my studies.

Laboratory setting
My dear lab bench at the Wyss Institute

What comes to my presumptions about Boston, at least one of them proved very accurate. According to the EPM Scientific (2023), this year, Massachusetts has earned the title of “the largest and leading Biotech hub in the world”. The life science and biopharmaceutical sector has grown massively in the Boston metropolitan area, this growth corresponding to increase in venture capital, employment rate, and governmental funding received. In fact, there are almost 1000 biotech companies, and over 60 colleges and universities in the area! Combine this with specialized medical centers and university teaching hospitals such as Dana-Farber Cancer Institute, Boston Children’s Hospital, Beth Israel Deaconess Medical Center, or Massachusetts General Hospital, and you have the foundation for boundless opportunities.

During my daily bike commute along the Charles River, not only could I enjoy the views of prestigious red brick buildings from the 18th century, but also appreciate the modern glass office buildings with biopharma company names like Biogen, Takeda, Pfizer, or Eli Lilly written on top of them. The different universities, non-profit organizations, venture capital firms and other groups were organizing various incubator and accelerator programs with pitching events open to attend for anyone interested. In addition, there were free of charge conferences, seminars, and lectures given by top scholars of the field, by people you had previously only seen in Ted Talks or had read their state-of-the-art work from Nature, Cell, and Science. You would see advertisements of novel RNA technology in the subway and randomly hear discussion of a given research topic in almost any bar or restaurant in the city. Even if you would go on a walk in a national park hundreds of miles outside Massachusetts, you would encounter other hikers with their company or institute swag, portraying very clearly the amount of biotech and medicine professionals in Boston and Massachusetts area.

Building with pillars and a yard surrounded by trees
The Quad at Harvard Medical School

For the work of our Brain Targeting Program and my internship this meant that I would be immersed into science, innovation, and biotechnology. Truly feeling like a child in a candy store. It was deeply inspirational and improved my thinking to be more creative yet critical. I could meet like-minded people and create networks with scientists working on topics of my interest. We could also work with clinicians and hospitals from around the corner and foster collaborations with other research groups somewhat effortlessly.

To conclude, I wanted to summarize three main learnings from my internship experience that are not only applicable to Boston but can be utilized in other contexts as well.

1. Keep an open mind

The amount of biotech companies and research initiatives makes it possible for anyone to find their research niche from Boston. There are hundreds and hundreds of job posts on LinkedIn, in positions rarely – if at all – seen back home in Finland. The challenge is not how to find what you would like to do, but how to choose from all the possibilities. That is why especially if you are in your early career, keep your mind, eyes, and options open.

Participate in different events, listen to talks from various specialties from academia and industry, talk to undergrads, PhDs, professors, R&D scientists, COOs, patient representatives… and you never know if you happen to sit next to a company CEO ready to hire a talent. Reflect on what you already know and have experience on, what would you like to learn, what is your aspiration, and get inspired. If you cannot travel to a big biotech center at this moment, see possibilities online or gather information and plan possibilities for a research visit, for example via funded traineeships or short training courses.

2. Networking is key

Sorry, I know you have heard this a million times, but it just is so important… All the opportunities and events you attend will also gather important and interesting people for you to meet. These people can provide you with valuable insights into your research and career or introduce you to other connections. So even if you would not necessarily consider yourself the most outgoing person and have always felt that networking is anxiety provoking and definitely not for you, dare to get in contact with and meet people.

In addition to introducing yourself and engaging into conversations spontaneously in events, you can send emails and meet people in person after you have had some time to think what you would discuss with them. It is not a bad idea either to review the speakers of an event beforehand and formulate questions you would like to ask them. In this way you will feel more confident and importantly, not waste anyone’s time. Even though the art of small talk is very much mastered in the United States, and it is a big part of the culture, people are busy and appreciate using their time well. Yet, avoid thinking of what you have to say is not of importance and because of it cause you not to talk to people. Despite their overbooked schedules, it was amazing to see how top scholars with over 100 000 citations would stop and truly listen to what you had to say, no matter in which career stage you were.

But in all, you will get the most out of these situations when you are clear and concise. Thus, tell honestly who you are, what you would like to do and learn, and ask for advice or even collaboration if you have a potential idea. You can also create a short pitch for yourself, it will help you to focus. And remember to be gentle with yourself, practice makes perfect.

People in an auditorium
Brain Targeting Program Consortium Meeting. Picture courtesy of the Wyss Institute at Harvard University

3. Have fun and explore outside the hub

Even though Boston, or any place you work and study, is such an exciting place considering your career, do not just biotech and network 24/7 – even if conversations with your friends would every now and then slip to the lab experiments and recently approved therapeutics. It is good to take some distance from constantly thinking about career and go explore the city and its surroundings. Go to the nature, delve deep into the history, visit art museums, join block parties, and enjoy the culinary scene. This will give you a full internship experience which should not be just fun science but fun experiences overall!

The HiLIFE Research Trainee Scholarship gives you a unique possibility to work and contribute to science nearly anywhere in the world and with a vast amount of life science topics. The opportunities for you to go after your dreams are out there. What will be your path?

 

Reference

EPM Scientific. (2023). Boston is Now the Largest Biotech Hub in the World. https://www.epmscientific.com/blog/2023/02/boston-is-now-the-largest-biotech-hub.

Following the swallows

Ecology field course in Kenya

At the hottest hour, we stop at a cliff for a lunch break. It’s January in Ngangao, one of the few protected montane forests remaining in Eastern Kenya. Everyone finds a rocky seat and starts digging their backbacks for lunchboxes. I have brought fresh avocados, passion fruits and mangos from the market place. This time we found both sweet and sour varieties of passion fruit. Someone asks a half-question about nature and our Professor, Jouko Rikkinen, seizes the moment and starts lecturing about lichens and lichen symbionts. I listen, but mostly for the beauty of it all. View behind him stretches hundreds of kilometers to the lowlands. Wind is soft and Ken, Darius and Mwadime are asleep and snore slowly. Swallows, such as barn swallows (Hirundo rustica), greet us with their spectacular airshow. I wonder if they are the same to which I bid farewell a couple of months back in Finland.

Taita Hills and a happy bunch of biologists

Jambo! I’m Maria Reiman, a Master’s student at the Master’s Programme in Integrative Plant Sciences. With the help of HiLIFE Trainee Conference Grant I was able to participate in Flora and vegetation of East Africa –field course (IPS-175) in Kenya in January 2023. In this blogpost, I’m going to share some of my key learnings as well as plant treasures of Taita Hills.

The course was organized by the University of Helsinki’s Faculty of Biological and Environmental Sciences, and our teachers on the field were Prof. Jouko Rikkinen, Mr. Mwadime Mjomba and Mr. Darius Kimuzi. The aim of the course is to learn about plant biodiversity in the area as well as climatic and environmental factors determining it. The Taita Research Station, established by the University of Helsinki in 2011, served as a base to our field course. It is located at Taita Hills in southeastern Kenya, in the village of Wundanyi. The area has attracted many scientists from different fields but especially biologists and geographers as it is a very unique area biogeographically. Taita Hills are like a miniature of East-Africa with an elevation range from 500 to 2200 meters and ecosystems including dry grasslands to moist montane rainforests.

Learning in the field

Nature was our classroom for the week. Every day, we would go to a different mountain, walk up the slopes and wonder at everything around us. Picture a group of students and teachers walking very slowly, taking pictures, squatting and pointing at something. Our guide and driver Ken was always sighing like “I just can’t with these botanists…”.

Mountains are an exception to Africa’s very flat general landscape. This goes back to 100 million years ago when the ancient supercontinent, Gondwana, broke up. South America, Antarctica, Madagascar, Australia and India separated but the remaining middle part – Africa – didn’t go through massive mountain formations unlike the other continents. However, these movements formed Eastern Arc –mountain chain of Kenya and Tanzania. Taita Hills are the northernmost mountain range of Eastern Arc.

Map of Eastern Arc -mountains on the left (EAMCEF 2014) and map of Taita Hills on the right (Kaasalainen n.d.).

Taita Hills are one of the most important biodiversity hotspots of Africa. They are known for their moist forests and unique flora and fauna. The moist rainforests support high diversity of life. One explanation to this is that because water and temperature are not limiting factors, species can focus on competition with other species, leading to speciation and evolution. For example, in dry and only seasonally warm Finnish forests, there are usually only a few dominant tree species but Kenyan rainforests host tens or even close to a hundred tree species. During the field course, I learned at least 176 new species (or if not learned then at least took notes and pictures).

Rainforest’s canopy is multi-storey as plants compete for light. Taita Hills used to be a vast rainforest area but due to changing climate and its consequence, anthropogenic pressure, there are only a dozen forest patches left. Most are the size of a few hectares and some are 70-190 hectares. Many species have evolved in Taita Hills and are thus so called endemic species. The mountain peaks have acted like islands and some species have their own subspecies for every mountain peak due to diversification.

Plants of East Africa. The strangler fig (Ficus thonningii) uses other plant’s truncks to climb up since the competition for light in the rainforests is though and investing into one’s own truck is very energy-consuming. Impatiens teitensis and the Taita African violet (Saintpaulia teitensis) are endemic to Taita. As visually beautiful species, they are area’s flagship species that are used to spread awereness of area’s biodiversity. African violets are endemic to Eastern Arc –mountains that Taita Hills also belong to. They are popular houseplants as well as Zamioculcas zamiifolia that grows in dry lowlands of Africa and is thus a good houseplant in dry households. Coffea fadenii is also endemic to Taita and is commercial coffee’s wild relative. Crop wild relatives (CWRs) are important for food security.

People’s livelihoods, biodiversity and ecosystem functioning are interdependent

Taita Hills, like all mountains, provide many vital ecosystem services for humans. One of the most important is water. Water’s journey to Taita begins 200 km eastwards from The Indian Ocean. Moist trade winds flow towards Taita and condense to water when they hit the eastern forested slopes of Taita. In this sense, the mountains act as water towers. Montane forests capture and provide water for vast areas and households far below in the lowlands.

Deforestation of montane forests and climate change have led to decreased water security in the area. Clear-cutted forest land doesn’t catch water as well as montane forests and their vegetation would and ‘water tower effect’ is lost. Rains have become unpredictable and sparse. This has devastating consequences for humans and wildlife. When humans struggle, questionable methods are used to meet the living costs. Even more forest is cut to get livelihood from selling timber and firewood. This leads to a vicious circle where water is even scarcer. However, local authorities are taking action to stop the deforestation of remaining forests. These include e.g. guidance of agroforestry methods and reforestation with native tree species.

In Taita Hills, there are some reference areas like Mount Kasigau (1000 m up to 1600m), previously inhabited higher at the hills but people moved downhill when the issue with water arose. Currently, only the lower hills of Mount Kasigau are inhabited and there are no plantations. Mount Vuria (500 m up to 2200m) however, is largely under human pressure and deforestation is ongoing. Optimally, Mount Vuria would look like Mount Kasigau. On our hike at Mount Vuria we witnessed forest cutting and many invasive tree species. Invasive tree species and their plantations are a huge problem in East Africa. For example, Eucalyptus-plantations cause many wildfires because their bark is very fire-prone while the tree itself is very fire-resistant.

Mount Vuria (left) is largely under human pressure and covered with invasive species (pic by Maiju Kupiainen). Mount Kasigau (right) is not and it is covered with native afro-alpine vegetation.

Native and biodiverse montane forests maintain functioning ecosystems which in turn mean secured water supply and livelihoods for people. Nowadays, people are moving downhill to the lowlands which is good in terms of water security. However, this has increased the number of human-wildlife -conflicts when residential areas and wildlife territories overlap. Elephants and baboons can destroy crops but they are undeniably vital for lowland ecosystems and their ecosystem services. As always, the co-existence of humans and the rest of the natural world is complicated but the search for compromise is a necessity.

The joy and anger of finding things out

As botanists, we were of course very interested in individual plant species of Taita Hills. In addition, we gained a lot of insight about ecosystem dynamics and societies of the tropics that could never be learned from the books. We discovered new species, ecosystems and phenomena every day. The more we learned and understood, the wider our view of the natural world got. Access to this type of knowledge is a privilege that correspondingly means responsibility.

Developed countries such as Finland, produce most of the greenhouse gases yet the consequences are currently mostly suffered in the developing countries such as Kenya. Developed countries must learn to live within the planetary boundaries e.g. by carrying their responsibility, reducing emissions and stopping overconsumption. Actors of the developed countries – states, companies and inhabitants – have the resources for these actions and there aren’t any acceptable excuses for not acting. Liveable future for all lifeforms of the Earth is secured and determined only by actions done in this decade (IPCC 2023).

Getting a wider perspective of global change, such as climate change and biodiversity loss, meant anger caused by injustice, lack of actions and already unstoppable consequences such as deaths of people and endemic species. We are devastated by drought and deforestation in the area, which were largely caused by climate change or its consequential human pressure. Defending and fighting for the beautiful but threatened biodiversity and ecosystems of Taita Hills are also our duty. Our realities are linked and swallows migrating from their overwintering sites in Kenya to their breeding grounds in Finland are an evident symbol of that.

_________________________________________________________

Big thanks to station staff, teachers, faculty, steering board and everybody who made this field course possible. We students really appreciate this as we know that field courses are constantly threatened with tightening budgets. Thank you for understanding that skilled biologists are made in the field, not classrooms!

PS:

  • Fellow students and dear friends of mine have also written HiLIFE-blogposts about Kenya. Gabriela Lemoine wrote a post about her experiences with more reflection e.g. about native and invasive species as well as our teacher’s, Mr. Darius Kimuzi’s, innovative agroforest farm. Lola Fernández Multigner took part in Human-Wildlife Conflicts in East Africa –field course (EEB-306) organized also by the University of Helsinki. She describes the complicated relationship between elephants and humans in this post.
  • Kaisaniemi Botanic Garden has many East African plants. For example, you can find Saintpaulia teitensis in the African Violet Room, Ficus thonningii in the Dry Forest Room and Coffea fadenii in the Rainforest House! Pictures of these are earlier in the text.
  • Water’s Journey, a documentary (2022) about Taita Hills can be found in Yle Areena. Beautiful nature, daily life and current topics are displayed magnificently. Watch Water’s Journey here.

References

EAMCEF. (12.8.2014). Eastern Arc Mountains. The Eastern Arc Mountains Conservation Endowment Fund (EAMCEF). [Webpage]. Available: https://eamcef.wordpress.com/2014/08/12/eastern-arc-mountains/

IPCC. (2023). Climate Change 2023: Synthesis Report. Contribution of Working Groups I, II and III to the Sixth Assessment Report of the Intergovernmental Panel on Climate Change [Core Writing Team, H. Lee and J. Romero (eds.)]. IPCC, Geneva, Switzerland, pp. 35-115, doi: 10.59327/IPCC/AR6-9789291691647

Kaasalainen, Ulla. (No date). Taita Hills and Mt. Kasigau. Lichens from East Africa and elsewhere. [Blog]. Available: https://lichens.academy/taita-hills-and-mt-kasigau-kenya/

Laine, Toni. (2022). Water’s Journey. [Documentary Film]. Helsinki: Wild Heart Productions Oy. Available: https://areena.yle.fi/1-61218224

Niemelä, T. (2011). Vihreä Afrikka: kasveja ja kasvillisuutta. Norrlinia; Vol. 23. Luonnontieteellinen keskusmuseon kasvimuseo.

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! 

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

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

My battle against RNases

 

Hi! I’m Anna and I’m a Master’s student at University of Helsinki (UH) in the programme of Genetics and Molecular Biosciences. I am honored to have been chosen as one of the HiLIFE research trainees for the year 2023.

For as long as I can remember I have been interested in life sciences. Nowadays, my main academic interests lie in functional genetics, RNA biology, translational biology, and biomedicine. I received my Bachelor’s degree at UH and wrote my thesis on the canonical and non-canonical functions of aminoacyl-tRNA synthetases. That was when my passion for RNA and translation really began. Learning about and understanding the complex systems that facilitate the basics for life is something that fascinates me deeply.In my spare time I am an active board member in the student organization Svenska Naturvetarklubben (SvNK), where I work as the vice chairman for the year 2023. A large portion of my spare time goes to the student organization, but I also love to draw and do some science related arts and crafts (such as making earrings out of the elegant tRNA secondary structure). 

RNA is part of the central dogma of molecular biology, but it has many other functions in the cell beyond that. There is a lot of ongoing research on a variety of different RNA types, but there is still a lot to learn about one of the first discovered, and no less fascinating, RNAs: tRNAs. For a long time, tRNAs had been thought to be mere vessels for amino acids, that their only job was to bring the amino acid to the ribosome for translation. tRNAs are indeed essential players in the basics of the translational system, but they also have many interesting regulatory functions. tRNAs have been shown to have a part in both transcriptional and translational regulation, as well as apoptotic pathways (Avcilar-Kucukgoze, I. & Kashina, A. 2020). Recently discovered tRNA derived RNA fragments have been shown to regulate both transcription and translation in miRNA-like ways and are seen as a part of the ncRNA family (Liu et al, 2022).  

The research in Docent Peter Sarin’s RNAcious laboratory focuses on molecular modifications on tRNA nucleotides. All natural tRNAs have molecular modifications on some nucleotides, such as methylation, acetylation and pseudouridylation. These modifications are important for the stability of the tRNA molecule, stress response in the cell, and regulation of translation (Koh & Sarin, 2018). For instance, hypomodification of the anticodon loop of tRNA molecules can disrupt anticodon recognition and may cause issues in protein homeostasis (Koh & Sarin, 2018). Diseases that have been associated with issues in the tRNA modificome, sometimes called tRNA modopathies, are e.g., microcephaly, intellectual disabilities, and multiple cancers (Chujo &Tomizawa, 2021). Modopathies can be caused by mutations or dysregulation of certain enzymes, such as methyltransferases and pseudouridine synthases, that regulate the modification profile of tRNAs (Chujo & Tomizawa, 2021).   

We still have a lot to learn about the role of tRNA modifications in health and in disease. As Chujo & Tomizawa (2021) mention, we do not have a complete understanding of the general cytoplasmic tRNA modification profile in healthy humans, which in turn makes it difficult to study modopathies since we have no healthy reference. A big obstacle in the research of tRNA modifications has been the loss of molecular modifications during sample handling as well as lack of methods to identify all modifications and their exact location. The RNAcious laboratory does e.g., research on method development to identify different types of modifications and research on the role of tRNAs and tRNA modifications in viral infection.    

 

The research in RNAcious. From RNAcious laboratory website, 21.6.2023, https://www.helsinki.fi/en/researchgroups/rnacious-laboratory/research-topics-0

 

My HiLIFE traineeship at RNAcious started in the beginning of April, and it has been a great pleasure to work in a prestigious, diverse, and international research group. So far, I am involved in a project where the aim is to characterize tRNA modifications in different mouse organs. In addition, I am working on a project where the goal is to plan, produce and isolate hypomodified tRNAs. My work has e.g., comprised of protocol optimization, RNA and tRNA isolation, mass spectrometry sample preparation, In vitro transcription (IVT), IVT template design and protein production and isolation. It has been a privilege to work with pioneers in the field and share and ponder different ideas with them.    

 

 

One thing that I have concluded thus far is that all RNA researchers have one common enemy, RNases. Ribonucleases: the enzymes that seek to destroy what is dearest to us, and they reveal their destruction through smeary bands in polyacrylamide gels. That is why I comprised a short list below which includes a few different ways you can inhibit RNase activity.  

RNA work 101:   

  • Use nuclease free eppendorfs.    
  • Use 3% Hydrogen peroxide to clean counter tops and gloves (anything that may be in contact with the sample).    
  • Always use gloves when working with RNA to not contaminate your sample with RNases from your skin.    
  • RNase inhibitors are your best friend.  
  • Always keep your sample on ice. 
  • Heating samples at 80°C for 5 min should inhibit RNase activity.  
  • Store your RNA in -80°C to inhibit degradation.   

I am excited to continue this RNAcious journey and fight my own battle against RNases!           

 

References: 

Avcilar-Kucukgoze, I. & Kashina, A. (2020). Hijacking tRNAs From Translation: Regulatory Functions of tRNAs in Mammalian Cell Physiology. Front Mol Biosci 7, 610617.

Chujo, T., & Tomizawa, K. (2021). Human transfer RNA modopathies: diseases caused by aberrations in transfer RNA modifications. The FEBS journal, 288(24), 7096–7122. 

Koh, C. S., & Sarin, L. P. (2018). Transfer RNA modification and infection – Implications for pathogenicity and host responses. Biochimica et biophysica acta. Gene regulatory mechanisms, 1861(4), 419–432.

Liu, B., Cao, J., Wang, X. Guo, C.,Liu, Y., Wang, T (2022). Deciphering the tRNA-derived small RNAs: origin, development, and future. Cell Death Dis13, 24. 

On Thin Ice: Baltic Ringed Seals in Peril

 

Have you ever seen a seal in Helsinki? Count yourself lucky if you have (I, for one, have yet to see one). However, there was a time when ringed and grey seals thrived throughout the Baltic Sea. They would gracefully search for fish along the coast and take leisurely breaks on beaches and sea ice. Sadly, today they have become a rare sight, with ringed seals in particular confined to a few scattered locations across the Baltic.

Now, here’s a little about me: I’m no biologist. In fact, my last biology course was almost a decade ago. However, those who knew me as a child can vouch for my infamous obsession with wildlife. After obtaining my Bachelor’s degree in engineering, I spent several years working in financial services. But now, after a decade-long detour, I find myself returning full circle to my childhood passion, albeit with a twist. Recently, I completed my first year in the Master’s Programme in Life Science Informatics (LSI) at the University of Helsinki, with a specialization in mathematical ecology.

Just a few weeks ago, I embarked on an exciting 4-month internship funded by HiLIFE. During this internship, I will be working alongside the Environmental and Ecological Statistics Group at the University of Helsinki and the Natural Resources Institute Finland (Luke). Together, we aim to develop mathematical and statistical models that can predict future population sizes of Baltic ringed seals, and if things go well, perhaps grey seals too. We are particularly interested in the effects of hunting, fishing and climate change.

A ringed seal (Pusa hispida).
Image credit: Kingfisher, CC BY-SA 3.0, via Wikimedia Commons

The Past and Present of Ringed Seals

The history of Baltic ringed seals stretches back over 10,000 years. As the glaciers receded during the last ice age, these remarkable creatures migrated into the Baltic region. Over time, the changing climate forced them further north, eventually leading to the isolation of the Baltic population from their Arctic brothers and sisters. Today, these seals are adapted to the unique conditions of the Baltic Sea, and are considered a distinct subspecies.

 

Unfortunately, the journey for Baltic ringed seals has not been without challenges. Humans have been hunting these seals since their arrival in the Baltic, initially employing traps, harpoons and nets, and later transitioning to firearms. In the early 1900s, conflicts with fisheries prompted the implementation of bounties on ringed seals in the Baltic states. These hunting practices, coupled with chemical contamination in the Baltic, posed severe threats to the population.

The consequences of these detrimental factors became evident as the population plummeted from an estimated 200,000 individuals in 1900 to just a few thousand by the 1970s. The chemical contamination led to widespread female sterility, exacerbating the decline. Today, the Baltic ringed seal population is fragmented into four sub-populations in the Bothnian Bay, the Gulf of Riga, the Gulf of Finland, and the Archipelago Sea.

Subpopulations of the Baltic ringed seal (Pusa hispida botnica) and their estimated population sizes.
Image adapted from: Halkka, Antti, and Petteri Tolvanen. “THE BALTIC RINGED SEAL.”

Future Threats

Despite some progress in mitigating the threats faced by Baltic ringed seals, uncertainties loom on the horizon. The ban on seal hunting and the discontinuation of using harmful substances such as DDTs and PCBs in the late 20th century have contributed to the recovery of ringed seal populations, particularly in the Bothnian Bay. However, the status of the remaining sub-populations remains uncertain.

In recent years, rising seal populations in the Bothnian Bay have led to conflicts with coastal fisheries. To address these conflicts, hunting has been reinstated as a management strategy. Balancing the needs of both seals and fisheries is a complex challenge that requires careful consideration and effective management decisions.

In addition to hunting and chemical contamination, Baltic ringed seals are threatened by entanglement in fishing nets. The unintentional capture of seals in fishing gear poses a potentially serious danger to their survival and calls for the development of sustainable fishing practices that minimize bycatch.

Another pressing concern that looms over Baltic ringed seals is climate change. These seals heavily rely on sea ice for their survival. They construct lairs on thick and stable sea ice, where they overwinter, give birth, and raise their pups. Sea ice also serves as a crucial resting and molting platform for them. However, as climate change accelerates, the loss of sea ice becomes an imminent threat to their habitat.

Illustration of a ringed seal pupping lair. The lair provides shelter to
newborn pups from harsh winter weather, predators and even pathogens. Loss of sea ice and reduced snowfall due to climate change are likely to have significant negative effects on pup survival.
Image credit: Robert Barnes, UNEP/GRID-Arendal.

The extent to which the loss of sea ice will impact seal populations remains uncertain. Predicting the future dynamics of seal populations in the face of climate change requires sophisticated mathematical and statistical models that can account for various ecological variables and complex interactions.

The Role of Mathematics and Statistics

In the realm of wildlife conservation and population dynamics, the use of mathematical and statistical models plays a crucial role. These models enable researchers to predict and understand the consequences of various management decisions, thereby aiding decision-making processes.

During my HiLIFE funded research project with the Environmental and Ecological Statistics Group, my goal is to construct a Bayesian State Space Model (SSM), which is a type of hidden process model. As the name suggests, hidden process models aim to infer processes that cannot be directly observed. In the case of Baltic ringed seals, our knowledge of the population is based on hunting reports, interviews with fisherman, and annual surveys that count the seals hauled out on ice. However, the true underlying process, encompassing the births, lives and deaths of seals, remains hidden from our direct observation.

Bayesian SSMs provide a powerful tool to unravel the hidden dynamics of seal populations. By combining available data with probabilistic modeling techniques, we can make informed inferences about what is happening “behind the curtain”. These models enable us to estimate demographic rates, assess population trends, predict the effects of management decisions, and gain deeper insights into the complex dynamics of Baltic ringed seals.

A candid photo of my deskmates.

My First Weeks on the Job

During my initial days, I dedicated a significant amount of time reading up on ringed seal biology and learning about the application of state-space models (SSMs) in wildlife population dynamics. Once I gained a reasonable understanding of the ringed seal lifecycle, I constructed a simple age-structured model of their population dynamics. Through the use of Bayesian techniques, I inferred key vital rates, such as age-dependent fertility and mortality rates, achieving a good fit to the available data.

Over the next few months, my objective is to gradually enhance the complexity of this model, striving to develop an SSM that incorporates the intricate mechanistic details of ringed seal biology, as well as the effects of hunting, fishing and the loss of sea ice due to climate change. Among the major challenges ahead is the modeling and inference of density-dependent processes. No population can grow perpetually. Whether it’s the availability of food, space, or the presence of predators, there will inevitably be limiting factors. Unraveling these factors for ringed seals poses a significant challenge, especially since the population is currently rebounding from historically low numbers. However, understanding these limitations is crucial if we are to make meaningful predictions about the future of ringed seals.

It is precisely these kinds of challenges that make research truly exhilarating, and I consider myself fortunate to be confronted with them!

Gabi goes exploring… Kenya!

Jambo! I’m Gabi. Currently a second year masters’ student of the Integrative Plant Science programme. In January I went on a three week expedition to Kenya, far from the Finnish winter, to participate in two field courses. Together with my fellow students we followed various experts around to learn about the natural world in Kenya. In my first week I went with aspiring botanists to the Taita Hills research station in South East Kenya. Where the collaboration between the University of Helsinki is most apparent when you stand in front of the small but expertly built sauna, which seems oddly out of place in the mountainous region of Kenya. In the second and third week I went traipsing through the Kenyan savannah learning about human-wildlife conflicts under the guidance of three seasoned conservationists.

 

Week 1 – The secret life of botanists

What do botanists do? They look at plants. And that is exactly what we did. Adorned with a hat and lathered in sunscreen, we hiked up various hills and mountains stopping every 2 to 3 metres to admire any photosynthesizers, both big and small. The forests hold a wide range of unique plants, from the small Commelina benghalensis with its blue petals to the tall Newtonia buchananii tree with its sturdy buttress roots that support an impressive trunk reaching far above our heads. 

Taita Hills is an important water catchment area. Water captured here supplies large areas of the country. Therefore, changes that occur in this area have far reaching consequences beyond the local towns. Due to the persisting drought people are forced to seek resources from the forest. Human disturbances include collecting firewood and harvesting plants for livestock fodder. On Mount Vuria, one such harvested species is Dracaena afromontana. Few individuals remain in areas that used to foster an abundance of the narrow stemmed shrub with its long and slender leaves. Besides this, the spread of introduced species such as Lantana camara presents a real nuisance. They will sprout back when they are cut down and are fire resistant.

There was a clear distinction between forests that had a high human disturbance compared to relatively intact forests. In disturbed forests we encountered more non-native plants, such as Eucalyptus spp. and Grevillea robusta, both from Australia. They are important sources of timber. Yet, in these arid regions, Eucalyptus trees are considered problematic for forest diversity. As part of its ecology, a Eucalyptus tree sheds its bark, which increases the risk of wildfires and their spread. Moreover, its leaf litter changes the soil pH to become more acidic, which favours its own propagation, but disadvantages local species. 

Aside from visiting the forests, we were invited to Darius’ farm, one of our field guides. His sloping plot of land left us in awe. He implements different intercropping strategies and combines improved and traditional crop varieties; the former for the yields and the latter to maintain a diverse gene pool. His approach is in stark contrast with the large monoculture plantations of sisal (Agave sisalana). Originally from Mexico, this fibre crop has been planted in rows as far as the eye can see. We drove past kilometres of saw-edged rosettes that have replaced native trees, shrubs and herbs.

After a week of vigorous hiking and plant inspecting, we ended the course with a feast and a bonfire. We said farewell to our field guides, the station staff and Taita Hills. With the first week behind me and the second week about to start the focus of my expedition shifted from flora to fauna.

“What I see vs. what the plant sees”

 

Week 2 – Putting the wild in wildlife

All facts are fun but some are more fun than others. Did you know that cheetahs have non-retractable claws? They are so fast that they need maximum grip when chasing prey. Did you know that the aardvark is closely related to the elephant? After spending two weeks with animal enthusiasts I’ve stocked up on some of these fun facts. The one I want to share most of all is the propeller tail of Africa’s most dangerous herbivore, the hippopotamus.

While defecating hippos will swing their tails energetically. In the water this results in an even distribution of nutrients, which is appreciated by fish and other aquatic organisms. By bringing nutrients from terrestrial to aquatic systems hippos fulfil an important ecological role, one that fishermen value in particular. On land, this Jackson Pollock technique is used to mark their territories and, unintentionally, to entertain the two jeeps packed with ecology students. They are very territorial and males will fight savagely to defend their patches of land and water. I don’t recommend getting caught between one of these grim neighbour disputes. Conflicts between humans and hippos arise when humans unknowingly cross paths with hippos. Hippos will not shy away from confrontation and running away won’t do you much good as they have no trouble keeping up. 

You may already know that vultures are excellent scavengers. But did you know that vultures have great vision too? While gliding in the air they will keep an eye on their peers. If one swoops down, having spotted a recently deceased or dying animal, others will follow suit. So where there is one vulture there will soon be dozens. Due to a very acidic stomach (pH ≈ 1), they are resistant to various diseases, even anthrax. Sadly, they are experiencing drastic population declines, in large part because of secondary poisoning. This happens when people poison livestock carcasses in retaliation against carnivores such as lions, leopards and cheetahs. As vultures have a slow reproduction rate, individuals that die are not readily replaced. 

Continuing with this more sombre side of these ‘fun’ facts. When giraffe calves are born they drop from a height of 2 metres. In rare cases, calves die from that impact. Last one. Spotted hyenas have a very curious social hierarchy. Mothers can raise up to two cubs which are born with their eyes open and their pointy teeth already poking out. Soon after birth they fight for the position of dominant cub. The outcome of these first contests determines their social standing and impacts many aspects of their life.

 

Week 3 – Caught in the middle

In addition to learning about animal ecology, we set out to shed some light on the issues that arise when animals and humans meet. We wanted to learn from the locals how certain species cause conflict and what is being done to mitigate these issues. The communities we visited live in close proximity to wildlife. While most locals appreciate the animals and understand their role as a high-profit tourist attraction, large carnivores endanger livelihoods by killing goats and cattle. In contrast to Europe, where we have food security, in these parts anything that threatens people’s livestock poses a serious risk for survival. Therefore, it is not surprising that these attacks lead to retaliatory killing of carnivores. Indubitably, as conservationists we would prefer the animals to be spared, but it is rather arrogant to tell the locals that they should not defend their livelihoods. Frequently, farmers and pastoralists lack resources and know-how. Hence, conservation efforts often focus on showing locals how to better protect their livestock by fortifying their enclosures. Efforts also include informing them on the ecological consequences of poisoning carcasses and retaliatory killings. More controversial methods include building electric fences to keep animals in or out of certain areas. 

However, conservation is not as straightforward as a conflict between farmers and animals. There are many different stakeholders with their own interests that do not always align with the preservation of wildlife. Besides local subsistence farmers or pastoralists, you have landowners that determine who has access to the land and usually cater to the tourism industry. Not to mention the governmental bodies that make land use policies and add a layer of bureaucracy. On the other side, the integral part of this web is wildlife itself. They require space, which is encroached by the growing population and changes in land use. In the middle you will find the conservationist that is trying to consider the stakeholders while safeguarding the needs of wildlife. In many cases, rather than being a human-wildlife conflict it turns out to be a human-human conflict.

“I spy with my little eye…”

 

All in all

It has been an invaluable experience, both culturally and academically. I’ve been enriched by the colourful welcome from the Maasai and Turkana tribes in Leikiji, the banter of the field guides in Taita Hills and the remarkable endemic flora and fauna of the African savannahs. Many thanks to both the IPS and EEB master programmes for offering these precious field courses IPS-175 and EEB-306. Thanks to the HiLIFE Trainee Conference Grant that has eased the financial burden of this three week venture. And thank you reader for reaching the end of this condensed retelling of my African adventures!

Gabriela Lemoine

The elephant in the room: Human-Wildlife Conflicts

There are things you cannot truly learn by just reading about them. You can get acquainted with the concept, but if you want an in-depth understanding of it, you need to get rid of the distance and the intermediate messengers and go observe directly with your own eyes. As a biologist, I’ve acquired most of my scientific knowledge by studying. Now I’m studying a MSc degree in Ecology and Evolutionary Biology at the University of Helsinki, where I’m doing very variated courses that allow me to learn both about the underlying ecological and evolutionary processes that shape nature as we know it, as well as the current climate and biodiversity crisis and what can we do to stop it. I’m now getting more and more interested in the branch of conservation and applied science, which involves a human and social dimension. The required degree of empathy and comprehension in this area is hard to get if you are distanced from the environment and situation.

I recently had one of the most insightful experiences of my life. With the help of the HiLIFE conference grant, I went to Kenya for two weeks to take part in a course about human-wildlife conflict (HWC) in East Africa, which is part of my MSc programme and was organized by one of my teachers, Mar Cabeza. Before leaving, I had to prepare a brief presentation about one of the most conflictive species in the area: the African elephant. I talked to my mom about this presentation, and she was honestly surprised: “How can such a kind, smart and nice grass-eating animal be the source of conflict?”. My mom loves elephants, it would be a dream for her to see one in the wild. I love them too, of course, and I know they are essential for their ecosystem, aside from being beautiful. I could observe them in Kenya and it was a magical moment that I will never forget. But what I will also never forget is what we heard when we asked local people about them. “I like all animals, but I’m terrified of elephants”, a girl said.

The views from our campsite. On the other side of the fence, we could see giraffes and elephants

 

As a key part of the course, we organised focus groups and interviews with local people to hear about the HWC first-hand. This girl had some scary experiences with aggressive elephants that she couldn’t just forget about. Even though we had seen electric fences targeted at elephants all over the region, they are strong and smart animals, and they keep finding ways to trespass them. The risk of having a face-to-face with an elephant is high enough to have the population concerned. And this is not even the major source of conflict with elephants. These animals cause huge losses by crop raiding and infrastructure destruction, especially water structures like dwells. Droughts like the current one in Laikipia force animals to search for water and food in human settlements, so these incidents become more frequent. In communities with a subsistence economy, this is a serious threat to the population. Situations like this one increase tensions between the people and the wildlife and are counterproductive for conservation.

Some colleagues (and me, bottom-left) and local people participating in one of the activities during the focus group

 

At the same time, elephants might not be very happy about some human activities, I thought. Elephants migrate long distances, so when they find an obstacle impeding this movement, it’s logical to think they will try to overcome it. They can’t just decide to stop a behaviour shaped by evolution over thousands of years just because lately humans are building and expanding more than before. In Laikipia, several landowners have built elephant fences around their huge properties, often the elephants being more of an excuse than the actual reasons. Conflicts between different stakeholders (including farmers, nomad shepherds, ranch owners and private conservancies, among others) over the uses of and rights over the territory play a big role in determining the placement and extension of the fences. Consequently, the design of this alleged solution to HWC attends very little to what is actually needed, and, predictably, it fails to prevent any conflict. This doesn’t mean that elephant fences are useless. Maybe the small village we visited would be a safer place if it was surrounded by an elephant fence. Unfortunately, effective solutions are not usually that easy to implement.

The landscape at the community we visited in Laikipia

 

It is very easy, from a distance, to oversimplify conflicts like this one, where we search for “good” and “bad” characters among the stakeholders. There will always be interests with which we empathize more or less and that can lead us to mistakenly think that some perspectives or opinions are less relevant or not worth taking into consideration. As biologists, we have a tendency to talk about the relevance of conservation from an ecological point of view. It is a truth that elephants are ecosystem engineers and that they play a huge ecological role. Without them, the savanna wouldn’t look like it does, and all surrounding species would be affected in an unpredictable but guaranteed chain effect. We know we need to conserve elephants, that is our position as scientists, and we see this as such a big truth that we sometimes forget to consider other needs. But conservation is an essentially human discipline: we decide to conserve, what to conserve, when, where and, maybe most importantly, how to do it. It attends to our needs, it comes from us, and ignoring how people are affected by it would be a mistake.

The elephants we saw in front of our campsite, seen through my binoculars

 

“The people that are less to blame for global change are the ones that are suffering the worst consequences”

This is something one of our teachers said, and in this course, it stopped being just an idea that I heard. It became a reality that I could see with my own eyes. I got to see the dry landscape, observe the wildlife, hear about the conflicts from the locals and discuss and put together all the information we were receiving. Altogether, this course has reshaped my way of seeing conservation and completely changed my perspective. And I think this new point of view will make me a better scientist and conservationist in the future.

This has been, in a nutshell, and leaving many things out, my experience in this amazing course. Thanks for reading me! And thank you to HiLIFE for helping me join this course.

Lola Fernández Multigner

Extracting knowledge from flow cytometry data

Hi there, and welcome to the HiLIFE-Trainee blog! I’m Olivia Dreilinger, a second-year Master’s student in the Genetics and Molecular Biosciences program here at UH.

This winter I participated in Physalia’s course on Flow Cytometry Analysis with R/Bioconductor. The course was held digitally to facilitate a greater geographic range of students. Throughout the course, in addition to the lectures and coding sessions, I was able to interact with researchers and PhD students from all over the world. This made for an exciting learning environment. The conversations I had with the other participants about their work and career paths were especially inspiring.

And now, let me tell you a little more about flow cytometry, how we can analyze this fascinating data, and how I will apply this new knowledge in my work at UH.

Flow Cytometry
Flow cytometry is a powerful tool that can sort a complex mixture of cells, often from blood or bone marrow or cells from solid tissue that have been separated from each other (dissociated) into populations of different cell types. This can be used to count the number of cells belonging to a certain type or for downstream investigation of the cells such as gene expression analysis or functional assays. It has applications in cancer biology, immunology, infectious disease monitoring, and numerous other areas of cell biology. Here’s how it works: one by one, cells are sent through a machine which uses multiple laser beams to “read” properties of the cell. The machine does this by measuring how light is scattered in the forward and side direction and indicates the cell’s size and complexity (granularity) respectively. Additionally, the flow cytometry machine can detect fluorescence, making even finer distinctions between cellular subpopulations possible. Cells can be made to express fluorescent markers through staining, thus allowing for this higher level of resolution.

Once the cells have been sorted, the flow cytometry instrument returns a file regarding each cell’s fluorescent intensity with respect to each marker used. This data must then be analyzed in order to extract meaning and identify different cell populations, thus allowing for downstream research and diagnosis by comparing measures such as number of cells or mean fluorescence in each subpopulation of cells.


[Flow cytometry schematic. Cells are sent through the flow cytometry instrument one by one. The machine detects their properties and sends them to a computer for analysis. The cells can be separated by type for downstream analysis. Created with BioRender.com.]

Data Analysis
The trainee course I took focused on the step of turning the fluorescent intensity data into something meaningful about different cell populations. The first crucial step is preprocessing, which includes compensation, transformation, and cleaning—basically, the data needs to be tidied up for ease of use. Once this house-keeping task is complete, we can move on to the part we care about, namely identifying the cell populations.

The flow cytometry data can be displayed on a two dimensional plot with each axis representing the fluorescence of a given marker or how much light is scattered in a certain direction. The cells then cluster by type depending on their properties. Traditionally, these cell subpopulations were identified by eye and circled in a process called manual gating. This process can be repeated over and over again comparing different markers giving a complex gating strategy. The gating process can be automated with software packages in R such as FlowDensity and FlowSOM. This strategy looks at density of cells and uses it to determine the cell populations.

[A gating strategy for identifying cell populations. Here we can see the step-wise identification of cell populations, beginning by first identifying live cells, and then distinguishing which cells are lymphocytes from the other cells. From there, the gating strategy separates the cells that are granulocytes and continues finding subpopulations from those that are not granulocytes, and so on, using the properties of the light detected by the flow cytometry machine for each cell. Figures generated in Physalia’s Flow Cytometry Analysis with R/Bioconductor course, 2023.]

Current Research at UH
The Integrative Evolutionary Biology lab, where I am doing my thesis, uses flow cytometry to identify and investigate different types of color cells (or chromophores). We study cichlids which are tropical fish native to lakes and rivers of India, Africa, and South and Central America. There are thousands of different species of these fish with distinct and vibrant color patterns making them an exciting model system to study when it comes to the evolution of cell types and the composition of these fishes’ colorful skin. As shown below, there are a number of different chromatophores: melanophores which are dark in color, iridophores which appear iridescent and blueish, and xanthophores which are yellow. We are using flow cytometry to study the composition of cichlid skin across different species within the Cichlidae family. I’m excited to start applying what I learned in this course to our data.


[Images of the color cells (chromatophores) we are studying in cichlid skin. A) dark dendritic melanophores, B) iridescent, blue iridophores, and C) a close-up of a dendritic yellow xanthophore. Credit Alexandra Faur, Integrative Biology Lab.]

I am grateful to HiLIFE for awarding me the HiLIFE Trainee Conference Grant and to the Integrative Biology Lab for making it possible for me to participate in this excellent course, which deepened my knowledge of flow cytometry, and provided me with the tools to find meaning in this kind of data. I look forward to utilizing this technology in the future.

— Olivia Dreilinger