On how colorful fish fall in love in the dark

Have you ever stared closely at fish in an aquarium? Isn’t it just amazing to look at the plethora of shapes, colors, and different behaviors that the fish, living on the other side of the glass, display? My younger self really enjoyed the wonders of the aquarium hobby – I believe the underwater world bears some of the world’s most amazing representations of life, and those tanks could, in some way (ethical issues aside), depict a little part of these marvels. But, how do fish see each other? Are they attracted to the colors other fish display? If so, what happens then, in the dark?

I am Adrián Colino Barea, a Spanish wildlife biologist, and a current first year student of the Master’s Programme in Ecology and Evolutionary Biology at the University of Helsinki. My main motivation to join this programme here was to dig deeper in applied ecology in tropical regions, as the University of Helsinki has several research lines in the tropics. I am aiming to focus on biodiversity conservation: I want to contribute and make a difference to revert the trends that current human-driven impacts have on nature globally.

Not surprisingly, me in the outdoors, hiking, looking for some interesting endemics in Azores. Greatly attracted by field ecology, I would not have pictured myself doing this exciting lab-based internship back when this photo was taken!

While my passion has always been working on the field, touring the fish room of the Integrative Evolutionary Biology (IntEvoBio) lab during an introductory course of the master’s last year awakened my younger self thrill. Racks with tens of tanks full of cichlid fish from the African Great Lakes fill the room, all around us, while some of the IntEvoBio lab members, led by Prof. Claudius Kratochwil, guided us through the nuts and bolts of their interesting job with all these fish, and why they are so particularly wonderful.

African cichlids: the book example of speciation

The African Great Lakes are three massive freshwater bodies in tropical West Africa, originated by ancient tectonic shifts. However, these lakes have borne livable conditions for a relatively short time. A certain group of cichlid fish got to these waters and started evolving at an unprecedented rate, fitting every possible niche, and generating entire, complex ecosystems, all based in different cichlids. What is more, they display very different color patterns of colors, bands, and spots, and perform elaborated mating rituals. Their unusually fast evolutionary process is based in ‘sexual selection’, meaning that individuals choose others as partners based on certain traits of their preference, despite the fact that these traits could make them, for instance, more showy – and therefore easier to spot by predators, hence against ‘natural selection’ as described by Charles Darwin.

To put it in perspective, for any evolutionary biologist, the cichlids of the African Great Lakes are old acquaintances, and for some they are the entire reason for their research. For many biologists, they are just inexplicably special. Some even say that the basis of evolution today would be radically different, had Darwin visited these lakes instead of the Galápagos Islands almost 200 years ago, and looked to these fish.

While in the lab, I enjoyed seeing all of the complexity that I have read about, right before my eyes. The researchers explained to us how these fish (and their evolutionary process) strongly rely on color communication. They have developed color signaling to inform about their sexual status, the hierarchy within a group, and even some species can change their colors rapidly, to give fast information! 

Cichlids have evolved into a big variety of colors, shapes, and behaviors among the waters of the three African Great Lakes. Just to clarify, the big guy on top left is not a cichlid 😉

However, one of the drawbacks to this very fast evolutionary process is that it is also very fragile, as species may seem radically different in colors and shapes but have very similar DNA, because of how recently they have evolved. In addition to this potentially fragile evolution, these lakes are particularly vulnerable to the impacts of human development. Lake Victoria is the second-largest lake on the planet by area and a huge population increase, has led to 40 million people now inhabiting the coastal region This human activity has resulted in major issues related to biodiversity, mostly through pollution, overfishing, and introduction of invasive predator fish and floating plants. 

How does sexual selection work under deterred underwater light conditions?

In particular, an invasive floating plant, the water hyacinth (Pontederia crassipes), is causing terrible damage to all ecosystems in Lake Victoria, and migh spread to other lakes. These plants prevent light from penetrating, hindering the oxygen production in the water and making the ecosystems within it collapse. Moreover, the human communities around the lake cannot physically access their resources because of how dense and inexpugnable the floating mats are.

But, coming back to my initial concern, floating plants – as well as increases in turbidity – make the underwater dark. Is there anything happening directly to the cichlids? If they rely so strongly on visual communication for their daily lives and long-term evolutionary process, how do they cope under a scenario in which their vision – light supply – is hindered? How can they find and recognize each other effectively and ‘sexually’ select their preferred partners according to visual signals (colors)?

During my internship, beyond my research project, I am learning the basics of tank care and manipulating fish. I certainly work with beautiful animals, such as this Pseudotropheus (Chindongo) demasoni, and the yellow females of Ps. (Ch.) saulosi in the bucket.

Back during my lab visit, I asked some researchers and they didn’t have an answer. This visit was inspiring enough to raise meaningful biological questions, with profound biodiversity conservation meanings. I am very pleased that HiLIFE gave me the chance to shed light on this topic, by granting me a Research Trainee Scholarship. Since March, I can call Prof. Claudius Kratochwil my supervisor, and some of the PhD students that once showed me through their research, my helpful mentors. 

From March to today: the beginning of my experimental phase

During these months, I have been setting up my experimental arena, and dedicatedly come up with a protocol to follow. I am working on the mate choice of cichlid males over females under different light conditions. Only last week I started the experimental phase, and I am excited to know what will happen with the results that I am obtaining – I will keep you posted on my progress. If this experiment arise meaningful outcomes, these invasive floating plants would potentially be given a new threat to nature, and hopefully a new reason to focus efforts and find an effective solution in the field, for the cichlids, for the people in the region, and for the entire ecosystems.  

Climate resilient, biodiversity-based agriculture for sustainable development

 

Hello! My name is Letizia, and I am a first-year master’s student in Environmental Change and Global Sustainability at the University of Helsinki. Through the HiLIFE Trainee Conference Grant, I had the opportunity to participate in a one-week Seasonal School on agricultural development in Sant’Anna School of Advanced Studies in Pisa (Italy).

Sant’Anna School of Advanced Studies

The course was built with an interdisciplinary structure, and I had the opportunity to listen to experts ranging from climate science, to agronomy, genetics, and economics. This enabled me to have a better grasp of the complexity of the agricultural sector and of how essential cooperation between different fields is in order to reach agricultural development goals related to food security, sustainability, and climate change adaptation. In this blog post, I will share my experience throughout the week.

But first, why agricultural development?

Food is an essential element in a person’s everyday life. It lies at the base of one’s ordinary activities, as it provides the necessary nutritional requirements for survival. Since the beginning of humankind, the provision of food has stood at the foundation of human existence. Today, things have somewhat remained unchanged, whilst increasing in magnitude and complexity. A global agri-food system has developed, interlinking a wide range of actors and sectors, expanding on different scales and spatial dimensions. The issue of hunger, however, still remains very much relevant.

Agricultural field in southern Finland

An expansion of cultivated land, coupled with technical progress, has brought about a huge increase in agricultural productivity in the last century. Today, the quantity of food available can meet the nutritional needs of a population of more than seven billion people. This would have been an astonishing success, except for the fact that it has been accompanied by a very uneven access to resources and distribution of benefits. The world finds itself in front of a paradox, as there should be enough food for all, but almost a billion people are chronically undernourished and more than two billion face various forms of malnutrition. What is more, production intensification practices have caused enormous damage to the planet’s ecosystems, hindering its capacity to feed people sustainably in the future.

How to tackle a complex issue?

The agricultural sector and cropping systems, their structure, and dynamics are key in tackling these complex issues. Agricultural development has a fundamental impact on the reality of food and agricultural production, and it entails an interdisciplinary and intersectoral approach. This was exactly the goal of the course, as the week was structured in such a way that allowed students to have an encompassing and multifaceted vision of agricultural development and its challenges.

The course was structured in modules, and each day we would tackle agricultural development from a different discipline perspective. The first module was about climate science, and the nexus between climate and agriculture. The second module dealt with agrobiodiversity and the potential of agroecological practices and ecosystem services for sustainable agriculture. The third module focused on genetics and breeding methods, including alternative participatory ways to foster varietal development and adoption. The fourth module tackled the social elements in agricultural production, innovation implementation challenges, as well as and the role of inequality. Finally, the last day we tried to connect all the modules through a holistic view and cooperative approaches.

Interdisciplinarity is hard, but fun…

Overall, during the week the atmosphere was very friendly, inclusive, and
stimulating. I got to meet excellent professors, researchers, PhD students, and fellow students from all different fields. We had both traditional lectures, as well as group works, and a lot of interesting discussions! I would say that, if you want to know what it means to do research in an interdisciplinary group in a small university, this is a great way to do it. The location also played its role, as during the evenings we could enjoy the lovely city of Pisa and some great Italian food!

City of Pisa
Pisa tower

All in all, this opportunity has taught me even more the importance of interdisciplinary research and the value of committed individuals from different backgrounds working together to reach a common goal. I was very inspired from this week, and it helped me to understand a bit better what I would like to do in my future career. I thank Sant’Anna School and HiLIFE for this opportunity!

MANF: no longer a mystery?

Hello everyone! My name is Amanda Sandelin, and I have conducted my traineeship co-supervised by two groups at the University of Helsinki: Mikko Airavaara’s group of BrainRepair and Samuli Ollila’s group of Biophysical Chemistry. If you do not remember what my project was all about, you can refresh your memory here: https://blogs.helsinki.fi/hilife-trainees/2022/07/07/mystery-of-manf/. 

My summer as a HiLIFE research trainee 

My master’s thesis project is about MANF or mesencephalic astrocyte-derived neurotrophic factor. As I wrote in my previous blog post; MANF is a neurotrophic factor, which has protective effects in various disease models, including Parkinson’s disease. MANF mechanisms of action and function are somewhat of a mystery, so this summer I have been working on resolving the mystery of MANF.  

To study the function and structure of MANF, I have been conducting experiments both in vitro and in silico. During my traineeship in Mikko Airavaara’s group I have been working mainly with stem cells. We have a MANF knockout human embryonic stem cell line, which I have been using to study how the loss of MANF affects cellular antioxidant defense. I have also differentiated stem cells into human dopaminergic neurons to study the role of MANF in human dopaminergic neuron development. In Samuli Ollila’s group, we combine molecular dynamics (MD) simulations with nuclear magnetic resonance (NMR) spin relaxation data to study how biomolecules, including proteins, behave. I have been simulating MANF structures in different intracellular conditions using MD simulations and compared the simulations with experimental NMR spin relaxation data to validate the methodology for studying two-domain proteins such as MANF.  

During the summer I have done a lot of cell culturing, MD simulations, immunofluorescent staining, biochemical assays and data analysis. I have had the chance to design, conduct, analyze and discuss experiments and, finally, present my work in seminars and at a conference. So, all around a science-filled summer that has resulted in some exciting results coming your way soon!  

Thank you! 

Did I solve the mystery of MANF? Maybe not yet, but the mission continues, and I have exciting results that I am now compiling in my thesis. The HiLIFE research traineeship made this project possible, and I must thank my supervisors for being open to this collaboration. Thank you to Vassileios Stratoulias, Samuli Ollila and Mikko Airavaara for guiding me as a young researcher and for allowing me to pursue my scientific curiosity.  And, of course, a big thank you to HiLIFE for giving me this opportunity to work in an inspiring research environment!  

Wishing you a cozy autumn,

Amanda Sandelin

Moss mites may tell us about carbon cycling on peatlands

Hi all!

I’m Jemina, a Forest and Atmospheric Sciences student at Helsinki University. This summer I joined Minna Väliranta’s research group at the Environmental Change Research Unit (ECRU) as a HiLIFE Research Trainee. In this blog post, I will briefly introduce you to the hidden life of moss mites. I had the opportunity to investigate a topic new to the whole group and to begin working on my Master’s thesis on the subject.

Moss mite communities may tell us about carbon cycling on peatlands

Organic matter on peatlands is generated and decomposed continuously. Sphagnum moss stems reach up towards the sun while old growth beneath them begins to disintegrate. A mire is formed when growth is faster than decomposition and partially broken-down material compacts into peat. In anoxic conditions under water, peat releases carbon and nutrients very slowly. Peatlands are some of the most efficient carbon banks that nature has to offer. Sometimes, however, decomposition accelerates and exceeds the carbon sequestration of vegetation. This may happen on peatlands modified by human activities or because of changes in climate, but also as a result of the natural development of mires. Whether our peatlands will be carbon sinks or sources in the near future, and how long it will take for possible changes to occur, is a timely topic to research. These different kinds of trajectories are being studied at the University of Helsinki by my supervisor senior research fellow Minna Väliranta and her group.

But how does peat eventually break down? The most effective primary decomposers are microbes, changing the chemical composition of plant matter. Small soil organisms affect decomposition both directly and indirectly: by consuming plant material and other organisms, transporting microbes, and regulating the spread of fungi. Part of the decomposition process depends on the activity of moss mites, a group of tiny insects.

 

Hard workers underground

Moss mites (Oribatida) are arachnids less than a millimeter in size. Like their better-known relatives, mites have eight legs. Unlike ticks, they are not harmful to humans. On the contrary – without them forestry or food production would be significantly harder. Moss mites play an important role in maintaining the well-being of the earth, as they release nutrients back into the soil. Despite their name, moss mites thrive in a wide variety of environments and are abundant in deserts, anthills, tree foliage, fields, and mires. Hundreds of thousands of moss mites can be found in one square meter of forest soil!

About 12,000 moss mite species are known to the world, and the number is growing constantly as research is carried out. Moss mites can adapt to almost any kind of environment. Some of the species have adjusted to especially harsh conditions, and so mites can also be found in nutrient-poor, acidic and wet peatlands. These environments are demanding for other soil modifiers: for example earthworms cannot be found in peat. This is why moss mites are especially important in peatland environments.

The wide range of species also reflects on the moss mites’ menu. Some species are vegetarians, some enjoy fungal mycelium for food, and others are opportunists eating whatever comes their way. In addition to nutrition, other environmental conditions also affect which moss mite species thrive in each place. Moisture has been found to be an important distinguishing factor, along with soil acidity and phosphorus content.

Knowing moss mite species and their preferences is useful. When any certain species is found, we can deduce that the environmental conditions it requires are also met. Due to their small size, moss mites move very little during their lifetime. It has been noticed that horizontal movement can be just within tens of centimeters. They are also long-lived among insects and can live up to five years in cool habitats. Changes in the species composition in a certain place therefore also reflect a change in the environment. Monitoring of moss mites can show, for example, improving moisture conditions at a restored bog site.

While moss mite communities can tell us about the current state of mires and peatlands, they may also be useful when looking for information of the past.  As peat accumulates, not only plant material but also fossils of small organisms are buried in it. The layered peat deposits of a mire can be dated. By studying the moss mite species at chosen intervals, we can gain information about the environmental conditions that prevailed at the mire tens, hundreds or even thousands of years ago. Moss mites have a hard chitinous shell that survives decomposition quite well. However, small sensory hairs on the mites’ shells may break easily, which often makes it difficult to identify mites to the species level from fossil samples.

 

Oribatid mites have a hard, chitinous shell and eight legs.

 

Research is challenging due to the large variety of species

The microscopic size of the organisms and the large variety of species is a challenge in studying moss mites. Determining the species level of mites is hard, and differences between species are sometimes only detectable with the help of DNA research. When I started learning about moss mites, I also noticed that identification guides are poorly available and none of them are in Finnish.

The presence and activity of moss mites has, however, been studied in quite a wide variety of environments in Finland. Riikka Elo noticed in her dissertation that anthills support the life of rich moss mite communities. Inkeri Markkula showed in her work that certain moss mite species in the peat archives can tell us if permafrost has previously been present at northern mires. Ritva Penttinen, now retired, has had a long career in tick and mite research at the Turku University Zoological Museum, and has extensively mapped Finnish moss mite species.

In planning my own research, I have been most interested in the question of whether the moss mite community could tell us something about the rate of soil carbon decomposition. Since mites stay put in a very small area, the species composition can significantly change within the scale of just a few meters. By collecting moss samples from different kinds of mire surfaces and separating the mites from them, my intention is to compare the found species and their abundances with carbon flux measurements from each location. Doing research is always an adventure, and I still can’t be sure what I’ll find along the way! I will keep you posted as the research continues.

Crossing Continents: The journey of a budding neuroscientist

Hi everyone! My name is Anushka Wakade. In this blog, I am going to share
my journey from being just a budding neuroscience enthusiast to an
international HiLIFE trainee in the Neuroscience Center of Helsinki.

A Peek into my Life before Finland

As far back as I can remember, the workings of the human brain have
always fascinated me. The intricacies of human behavior and the fallout
that is seen when the brain glitches has never failed to intrigue me. As a
result, even as a bachelor’s student in life-sciences, I have tried my best to
go out of my way and read and obtain as much experience as I could on
this topic. During my extra honor courses and internships, I realized that
neurodegeneration, cognition and the link between the two appealed to me in this massively broad field of neurosciences. Keeping in mind that the next
logical step was to pursue my further education (as a master’s degree) in
the same, I started looking for master’s courses that were offering similar
experience in Europe (as neuroscience related research is expanding here
exponentially) . The master’s program in the University of Helsinki fit all my
expectations with respect to courses, practical experiences and exposure
to opportunities. Hence, it was not a difficult decision to finalize Helsinki
and move here for my further education.

Perks of being a HiLIFE Trainee

During my time as a HiLIFE trainee. I decided to join as a trainee in Dr.
Coralie Di Scala’s group in the Neuroscience Center. The lab is focused on
studying the lipid-protein interactions in nervous system diseases, with a
special emphasis on epilepsy. Having studied biochemistry extensively
during my bachelor’s, my interests and suitability to work in a group which
studies neurodegeneration from a biochemical point of view worked out
well for me to decide that I wanted to pursue my master’s thesis in the
same lab.
Temporal Lobe Epilepsy is one of the most common types of epilepsy
whose clinical definition is the presence of unprovoked recurrent seizures
over a period longer than 24 hours. Approximately 30 to 50% of epileptic
patients suffer from severe cognitive deficits (such as memory alterations)
whose severity only increases the longer they have seizures. Being one of
the most globally prevalent disorders, research concerning its
pathophysiology has been under work for a couple of decades now.
Unfortunately, no cure or aetiology has been identified so far. The current
anti-epileptic drugs used to counteract the intense symptoms have been
found to be ineffective in about one third of the epileptic patients. As a
result, the condition of epileptic patients continues to worsen, decreasing
their quality of life. For this reason, it is crucial to direct research towards
discovering the underlying mechanism of epilepsy, which would lead to
finding more effective therapies. Currently, there are quite a few theories
investigating this underlying molecular mechanism and one of the most
widely accepted for Temporal Lobe epilepsy is that the alteration of
chloride ion homeostasis in neurons causes a grave impact on the
synaptic (neuronal) communications in the brain, precipitating the
apparition of seizures. The disturbances in neuronal chloride homeostasis
in epilepsy are caused by the malfunctioning of the chloride ion
co-transporters present on the cell membrane, which are responsible for regulating the ionic flux between cells. Our laboratory is interested in exploring the missing or the unknown aspects of this specific theory. Dr. Di Scala’s lab has discovered that certain lipids present in the cellular membrane (Gangliosides) have specific and direct
interactions with these chloride cotransporters and hence also plays a
crucial role in maintaining it’s structural and functional integrity,
necessary for the normal neuronal functioning. Despite knowing the other
vital functions of gangliosides, no other research group has explored it’s role in
the pathophysiology of epilepsy and its potential therapies. In this way, the
laboratory is novel in its approach and explores avenues that have not yet
been taken into account for explaining the mechanism and progression of
this disease through modulation of these chloride transporters. This would open several avenues
for new therapies concerning epilepsy. The lab is currently focused on quantifying and then studying the interactions between these gangliosides (membrane lipid) and protein (chloride transporter) to get a fuller picture of the pathophysiology of epilepsy.

My thesis would be a sub-project of this larger research question
that the laboratory is tackling by focusing on the characterization of lipid
alteration during epilepsy.

I have been working on this for a couple of months but I still have a long
way to go before I wrap up my thesis. I am extremely excited and hopeful
for the results that will start rolling in soon. During this period, I have not
just grown as a researcher but also as a person. The support and
teachings by both my supervisors have been invaluable and I am sure they
will stay with me wherever I go next in my career! I will elaborate more on
this and my future plans in my next post once I finish my  thesis. Thank you for being interested! I will keep you updated!

Six Months after Country Hopping to Switzerland: Master’s thesis is submitted!

Hello again everybody!

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

What was my thesis about? How was it performed?

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

The main aim of my thesis was to test the effect of different extracellular matrix (ECM) proteins on gastric stem cell differentiation. The ECM is currently considered one of the key stem cell niche components3,4. As a matter of fact, several ECM proteins had been already established to have a specific location within the human gastric mucosa. Thus, we wanted to check if these proteins could influence stem cell maintenance or differentiation towards one specific cell type. The main workflow of the project was to seed gastric organoid-derived epithelial cells on the proteins of interest and check for stem cell markers or other gastric epithelial cell markers with quantitative polymerase chain reaction (qPCR) after some time.

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

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

And now, what is the next chapter?

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

 

 

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

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

Bests,

Rosa

 

Some (maybe) interesting links: 

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

Mystery of MANF

Hello everyone! My name is Amanda Sandelin, and I am a first-year (soon to be second-year) Master’s student in Translational Medicine. I am one of the HiLIFE Research Trainees of 2022, and I am conducting my traineeship co-supervised by two groups at the University of Helsinki; Mikko Airavaara’s group of Neuroprotection and Neurorepair and Samuli Ollila’s group of Biophysical Chemistry. My interest lies in neuroscience, but I am also interested in structural biology as a tool to help understand the details of what really is happening in our brains.  

The star of my project: MANF 

My projects revolve heavily around one protein, namely the mesencephalic astrocyte-derived neurotrophic factor or, easier said, MANF. Even though MANF is a neurotrophic factor, its characteristics differ significantly from other “traditional” neurotrophic factors. In fact, the mechanisms of action and functions of MANF are still quite a mystery. But why are we interested in this one protein? Well, what is known about MANF is that it has pleiotropic protective effects in various disease models, including Parkinson’s disease, and it is important in human development. By studying the mechanisms of MANF, we can better understand neuroprotection and identify possible new therapeutic targets. 

The next question is of course: how do we study this?  I work both in vitro and in silico, which means I work with cells and by computational models, more specifically human embryonic stem cells and molecular dynamic (MD) simulations.  Vassileios Stratoulias in our lab has established a protocol for differentiation of both wildtype and MANF knockout stem cells into dopaminergic neurons based on a previously published rigorous protocol. Using this setup, we can study the differences between wildtype and MANF knockout cells at different stages of development. In Samuli Ollila’s group, we use MD simulations and NMR to look at MANF on the molecular level and see if different conditions (such as different pH, ATP or ion concentrations) affect the structure and function of MANF.  

My first month 

I have been loving the first month of my traineeship, and I have already had a chance to learn a lot of things and immerse myself in science and research. I have been doing a lot of cell culturing, simulations, experiments, planning, analysis, and discussing and I even attended a conference, where I got to present a poster. Below are some images to really convey the amazing, science-filled month I have been enjoying. Thank you goes out to my supervisors, Vassileios Stratoulias, Samuli Ollila and Mikko Airavaara, and to everyone else in the groups for making my traineeship as great as it is. And, of course, a big thank you to HiLIFE for giving me this opportunity to experience research at its heart! 

Here you can read more about: 

Neuroprotection and neurorepair 

Biophysical chemistry 

Wishing you a lovely summer,  

AmandaSandelin

 

Meet the Aalto-Helsinki iGEM team 2022!

Hello! We are the Aalto-Helsinki iGEM team 2022 and here is a little bit about us and about our project.

First things first, what is iGEM?

iGEM stands for “international genetically engineered machine” and is a global synthetic biology competition between more than 350 teams around the world. We are a team of 10 highly-motivated students from both Aalto University and the University of Helsinki. The combined Aalto-Helsinki team has existed since 2014, but the team members are different every year. Last February, the 2021 Team chose us as the new members for the coming year, and since then we have been brainstorming about what our project should be. 

Every year, the team picks a research idea and spends the summer break implementing it in the lab, and then presenting the results at the Grand Jamboree (which this year will take place in Paris in October). As you can see, we have a very short time frame to organize, visualize, and prove our idea!

 

What is our idea?

After a lot of back-and-forth between several promising ideas, we decided to target biofilms on chronic wounds. Chronic wounds are found in 15 % to 25 % of diabetes patients and often lead to increased morbidity, mortality in general decreasing the quality of life, and are therefore of high public health concern. 

The environment of chronic wounds is usually low in oxygen (hypoxic) and thereby causes decreased immune activity. Therefore, bacteria can easily settle there, leading to the formation of biofilms. Biofilms are structural communities of bacteria that are usually tolerant to host defences and antibiotics. This is an issue for the patient, because treatment is more difficult.

Biofilms form when bacteria settle on the wound site, and their presence attracts even more bacteria through a process called quorum sensing. Quorum sensing is defined as population density measurement and a form of inter-microbial communication in the biofilm. The process of quorum sensing specifically works through bacteria releasing small molecules or peptides that other bacteria can take up, thereby sensing the presence of the other bacteria. Furthermore, bacteria can also auto-induce themselves via these peptides or molecules: indeed, auto-induction is a positive feedback-loop in which bacteria signal to themselves to produce even more of these quorum sensing peptides or molecules, through which further downstream gene activity and more biofilm build-up is achieved.

Our central aim is to target this mechanism to disrupt the formation of more biofilms.

For this we want to utilize DARPins. DARPin stands for designed ankyrin repeat proteins. They are genetically engineered peptides that mimic antibodies. We want to design DARPins that bind to the quorum sensing peptides released by the bacteria, which should prevent the “communication” between bacteria and obstruct the further build-up of biofilm. The end result we envision is for our designed DARPins to be used in combinatorial therapy with antimicrobial agents against biofilms, as blocking their signalling should make the bacteria more sensitive to such antimicrobials. 

 

Is that all?

In fact, iGEM is a lot more than just the research aspect. In addition to our main project, we also focus on developing different collaborations, as well as community outreach and science communication. The latter aspect is called Human Practices and represents a key foundation of the iGEM competition. As part of this, we are currently talking to many different experts in the field, including front-line medical staff, and are very happy to learn more about the practical considerations of wound healing. We will also prepare and hold a workshop at Heureka, and collaborate with The Science Basement. We plan to give a talk on the 24th of September during the European Biotech Week. We furthermore continue the Aalto-Helsinki iGEM podcast that was established last year.

So, if you want to know how everything is going throughout our project, you can follow us there or visit our blog.

 

Thank you for reading and thank you to HiLIFE!

Lastly, we also want to thank HiLIFE and the University of Helsinki for supporting us and our idea during the iGEM program and for enabling us to join this competition. We are very happy to be part of iGEM and cannot wait to get started, working to make our theories a reality! 

International HiLIFE Trainee: Addicted to Country Hopping

Hello everybody!

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

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

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

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

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

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

My contribution to the lab’s main goal is to test the effect of different ECM proteins on gastric stem cell differentiation and regulation. Human gastric organoids are not as well characterized as human intestinal organoids, as a matter of fact, not all the cell components of the human gastric glands are able to be differentiated in the common 3D organoid model4. On the other side, the focus on the extracellular matrix (ECM) as a key niche component of stem cells has exponentially increased in the past years5,6. Therefore, I am researching whether bioengineering a synthetic hydrogel enriched with different ECM proteins can modulate human gastric stem cell regulation and differentiation to improve the pre-existing 3D organoid model.

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

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

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

HiLIFE TRAINEE ATTENDING THE ASHG21 ANNUAL MEETING

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

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

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

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

Celia Gómez Sánchez