Digging for new breakthroughs A MAGAZINE FROM SCILIFELAB
#1 –– 2017
New magazine!
More inside Is it possible to restore hearing? To lead research is like running your own business New method for treating rheumatoid arthritis
Report from the
underground – life where the sun never touches
A magazine from SciLifeLab
Synergy #1 –– 2017
1
Foreword Welcome to the first edition of Synergy magazine!
S
ciLifeLab contributes to thousands of research projects every year. In this magazine, we wish to highlight a few examples of these projects. We will feature the scientists, their work and the goals behind their research. At the same time, we want to show how research initiatives can contribute to improving health and environment. One of SciLifeLab’s missions is to bring researchers from various fields together to make use of the latest technologies and infrastructures in order to generate added value for their research and to open opportunities for health care, industry and society in general. That is why we named the magazine Synergy. Since its inception in 2010, SciLifeLab has offered technologies and services to researchers throughout Sweden. Through financial support from the government and other funding agencies, we have been able to give researchers access to the latest technologies, expertise and equipment at an affordable cost. In the Synergy magazine, we hope to demonstrate the opportunities we offer, so that you can gain new ideas on how to use SciLifeLab’s services for your own research. Synergy is published twice a year. In this very first edition, you can read about Kristina Broliden, professor of infectious diseases at Karolinska Institutet. She has been investigating HIV since the mid-1980s and is currently involved in two major projects. We also feature Mark Dopson, who emphasizes that we do not need to leave planet Earth in order to find new life forms. He is discovering new microorganisms deep in the ground. By understanding how such organisms survive in extreme environments, with neither sunlight nor oxygen, we can also better understand life above the ground.
Editorial staff
Synergy is a magazine about research, published by SciLifeLab twice a year in Swedish and in English. The magazine may be ordered free of cost, or read online at scilifelab.se/research/synergy Editor: Sara Engström Editorial committee: Ellenor Devine, Annica Hulth and Camilla Wernersson Photographer: Mikael Wallerstedt unless otherwise stated Design and production: zellout.se Printing: Danagård Litho Contact: synergy@scilifelab.se
Photo: Daniel Rosik
I wish you a thrilling reading experience.
Olli Kallioniemi, Director of SciLifeLab director@scilifelab.se
SciLifeLab (Science for Life Laboratory) began its operations in 2010 and is a partnership between the Royal Institute of Technology, Karolinska Institutet, Stockholm University and Uppsala University. In 2013, the government tasked SciLifeLab with creating a national center for molecular biosciences. The purpose was to be able to offer access to researchers throughout Sweden to technology and expertise for advanced research at a reasonable cost. SciLifeLab is fully integrated into the higher education institutions’ operations and is not for profit. SciLifeLab’s vision is to be a national hub for molec ular biosciences. Today, over a thousand research groups per year use the center’s services.
2
Synergy #1 –– 2017
A magazine from SciLifeLab
Contents 11 14 13
06 05 12
16
#1 –– 2017 02 / Foreword
06 / Mark Dopson
13 / Susanne Lindquist
Welcome to the first edition of Synergy magazine!
Report from underground – life where the sun never touches
New method for treating rheumatoid arthritis
04 / In brief
11 / Helge Rask-Andersen
14 / Kristina Broliden
SciLifeLab is on YouTube, lucrative socializing, and more
Is it possible to restore hearing?
To lead research is like running your own business
05 / Åsa Torinsson
12 / Björn Lindahl
16 / Mårten Fernö
Unusual career choice when Åsa was offered her dream job
Digging for new breakthroughs
Hello there!
A magazine from SciLifeLab
Synergy #1 –– 2017
3
In brief
238
researchers were accepted last year to one of SciLifeLab’s bioinformatics courses. There is a high demand for bioinformatics training in Sweden, which is why SciLifeLab offers courses to researchers from all over the country.
3 751 193 service projects were carried out by SciLifeLab in 2016.
SciLifeLab is on YouTube Check out our video about SciLifeLab on YouTube with information on research, education, collaboration and various services. Use the link http://bit.ly/SciLifeLab-5min
Lucrative socializing AIMday is an event at which the business community and the academic research community regularly meet to address the challenges faced by companies. To register and for more information, visit the website at aimday.se
“... a national resource that facilitates research and diagnostics related to genetic diseases ...” Thanks to a large DNA sequencing project, SciLifeLab has developed the first map of genetic variation in the Swedish population. The project is part of SciLife Lab’s effort to fund national projects in genomics and was enabled by support from the Knut and Alice Wallenberg Foundation. The result is based on analyses of the genetic material from 1,000 individuals selected from all over Sweden, and reflects the genetic structure of the Swedish population. Researchers have thus obtained a national resource that facilitates research and diagnostics related to genetic diseases. What was the purpose of the project? “To better understand the causes of our common diseases. Simply put, this
4
Synergy #1 –– 2017
is a catalog of the population’s genetic variations,” says Ulf Gyllensten, project leader and professor of medical molecular genetics at the Department of Immunology, Genetics and Pathology, Uppsala University and SciLifeLab. How can the result be used? “Clinical geneticists can assess whether a genetic variant in a patient or family exists in the healthy population, or if it is a likely cause of disease. In addition, the map serves as a control group against which we can compare different patients in genetic research projects to identify genetic variants that influence the risk of developing a disease.” The project is part of SciLifeLab’s effort in Swedish genomic research and will enable large groups of patients to get the right diagnosis and treatment early on in the course of disease. The database can be found at swefreq.nbis.se
courses, workshops and lectures were organized or contributed to by SciLifeLab in 2016. Of these, no less than 72 educational opportunities were held in cities other than Stockholm and Uppsala.
Seen in the columns 681 different scientific publications used data and analysis support from SciLifeLab last year, or reported on the technological developments that took place at the center.
All scientific publications associated with each article in Synergy can be found at scilifelab.se/ research/synergy
A magazine from SciLifeLab
Interview Text: Kristina Tilvemo / Photo: Mikael Wallerstedt
Unusual career choice when Åsa was offered her dream job. Often, our choice of profession is determined by chance. For Åsa Torinsson Naluai, a light bulb moment came early – already during her master’s program at the University of Gothenburg. A lecture in clinical genetics by Professor Jan Wahlström changed everything. After the lecture, Åsa Torinsson Naluai had decided: she would do her master’s project in clinical genetics. This was not easy to arrange, but she did not give up and after six months of persistence, Åsa got her way. “In the end, I did my master’s project on psoriasis,” rem embers Åsa. And the rest is history. A few years later, Åsa graduated with a PhD on the subject of celiac disease (gluten intolerance) from the University of Gothenburg, and if she was not fully committed to science before, she was then. “When I was finished with my doctoral dissertation, no one showed any interest in taking over and continuing that line of research, but there was a little money left, so I continued the project which was initiated during my PhD,” Åsa explains. If Professor Jan Wahlström’s lecture was one decisive moment for Åsa’s choice of profession, the Wallenberg Foundations focus on infrastructure in ‘omic’ technologies was another. Åsa Torinsson Naluai got the position as operative manager for the newly launched genomics center at the University of Gothenburg, and simultaneously, the opportunity to continue searching for connections between gluten intolerance, inflammation and genetics. “It was really an unusual career choice. The typical path is to first apply for a post-doc abroad to get further training, but this was, and is, a dream job. I landed a permanent position and at the same time the chance to continue my research,” Åsa says. For assistance, Åsa has had several PhD and master students in her group and the team also collaborates with other research groups. They study hereditary connections between celiac disease and autoimmunity. At their disposal, among other things, they have a bank of 400 small intestinal biopsies from children. This type of biobank is not found anywhere else in the world. On some days, Åsa sees no end to the work and she can become frustrated by the slow rate of progress, but the flame that was ignited during her studies by that magical lecture on clinical genetics continues to burn. “It probably burns even stronger now. In recent years, thanks to SciLifeLab’s technology, we have made a number of discoveries that may lead to real change for patients. It feels incredible to have been entrusted, with the help of public sector funding, to research things that will hopefully let us understand and cure more diseases in the future.”
Technology and service In her research on hereditary links between celiac disease and autoimmunity, Åsa Torinsson Naluai has used SciLifeLab’s genotyping service to map families with celiac disease. SciLifeLab has also assisted with amino acid analyses and bioinformatics expertise.
A magazine from SciLifeLab
“In recent years, thanks to SciLifeLab’s technology, we have made a number of discoveries that may lead to real change for patients.” Synergy #1 –– 2017
5
Reportage
Report Professor Mark Dopson’s natural environment is not entirely unlike the one he spends his time researching. While he may thrive above ground, he is happiest in the shade, a comfortable distance from the spotlight. We will follow him far beneath the earth’s surface via the sea floor and mine shafts. There is life that people are unaware of, but we don't need to leave the planet to discover and study it. Text: Anna Jansson / Photo: Mikael Wallerstedt
underg 6
Synergy #11 –– 2017 Synergy#
AAmagazine magazinefrom fromSciLifeLab SciLifeLab
Reportage
t from – life where the sun never touches
ground AAmagazine magazinefrom fromSciLifeLab SciLifeLab
SSynergy ynergy ##11 –– 2017
7
T Reportage
he sun that greeted me at the airport in Kalmar has disappeared by the time I am standing outside Linnaeus University down in the harbor. Instead, a cloud layer blankets the city and ocean. The sense of being underground, shielded from the rest of the world, could not be more appropriate. Mark Dopson meets me at the door and welcomes me as we walk inside the building. Although I have yet to see the laboratory, there is no doubt that research is being carried out in this building: the corridor walls are papered with posters about projects and research findings. Mark was born and raised in Surrey, just outside London. After his university studies at Nottingham Trent University, he applied for a doctoral position at Umeå University, moved to Sweden and met his future wife. Except for a two-year postdoc at the University of East Anglia in England, he has been in Sweden ever since. After a few more years in Umeå with a faculty position as a research assistant, Mark was offered a position at Linnaeus University in Kalmar and the family moved to Färjestaden on Öland. “It’s a special feeling to ride across the bridge after a day of work; Öland has really become home,” he says. Do you think you will move to England at some point in the future? “No. Sweden is great in many ways, especially if you have a family. [Mark and his wife have two daughters, editor’s note.] I also enjoy smaller cities: London was never right for me and like Surrey, this is a comfortable size; it’s perfectly
8
Synergy #1 –– 2017
lagom [“just right”] for me. Did you hear that? I said lagom. Sweden and I are a perfect match.” Mark and his group conduct research in four areas that are all related to the sequencing of microorganisms in extreme environments beneath the earth or water surface. One of these environments is the deep biosphere, i.e., up to several kilometers beneath the earth’s surface, where the pressure is high. Despite a distinct lack of nutrients, vast quantities of microorganisms live and thrive here. But they grow very slowly, and the generation time may be upwards thousands of years. Currently, Mark is looking at microorganisms at a depth of 460 meters in the Äspö tunnel outside of Oskarshamn. Naturally, the question is what is present down there, but also how the organisms live and how their metabolism functions. Among other things, he has found one of the world’s smallest organisms that lives independently and not inside another cell. This deep biosphere portion of the research is so-called basic research. Researchers do not yet know what the discoveries may lead to in the future, but are still studying and mapping the environment. The primary focus is on finding, identifying, and studying new kinds of life on our planet - life which most of us have never come into contact with. What is so exciting about life underground? “The fact is that 20 percent of the mass of all plants, animals, people and other organisms on earth live far underground. So you understand how many micro organisms there are. Obviously, we wish to know more about them – how they are impacted by and adapt to these kinds of extreme conditions,” says Mark. He finds the microorganisms underground, in groundwater contained in bedrock fractures. “The deeper underground we go, the older the water. The organisms that live here have been separated from the earth’s surface for a very long time, maybe up to several million years. Life that is funda-
mentally different from what we know above ground,” says Mark. So far, through DNA sequencing of the microorganisms, Mark’s discoveries have included species previously unknown to humanity. By examining the DNA of these organisms, Mark can conclude that they may have an unusually simple metabolism, something that contributes to their ability to survive in this special environment. Simply put, they use very little energy to survive. Another important part of the sequencing is to discover and study viruses since there are very likely new kinds that we do not know about. Here, the team primarily examines the interplay between viruses and microorganisms such as which viruses infect which microbes. Mark hopes to have access in the near feature to deeper environments than those being studied today. “We have applied for funding to drill to 1,500 meters deep. We still have very limited information about life down there. We don’t know what we will find, but we know there’s life,” Mark says.
T
he second environment the team focuses on is what most people recognize from annual reports of algal blooms in the Baltic Sea: dead sediment. Algal blooms cause the dead sediment when the algae sink to the sea floor, where the organic carbon is degraded by bacteria, consuming all the available oxygen and leading to the death of the sea floor. Mark’s primary interest is to find which microorganisms live in the oxygen-poor environment and how they affect the sediment. For example, what happens if we add oxygen? How do the organisms react and how is the environment ultimately affected? Through small-scale studies in which oxygen is added, the team wants to understand the process such as if harmful gases are generated and if they are removed by microorganisms? There are currently no complete answers to these questions, but some trends are evident. The group can conclude that microorganisms generate
“The organisms that live here have been separated from the earth’s surface for a very long time, maybe up to several million years.” A magazine from SciLifeLab
Reportage
RNA coding for the breakdown process when oxygen is supplied. Of course, the big question is whether people can actually revive the anoxic sea floor in the Baltic Sea with the help of microorganisms by for example, pumping air into the depths. This would mean the return of plants, fish, and other animals to the site that will benefit the fishing and tourism industries. Who knows? Maybe in the future we can bring artificial breathing to one of the world’s most unhealthy seas. When Mark is asked what he enjoys doing in his free time, nature is the theme. All those years in Umeå left their mark and outdoor life is at the top of his list of interests. “Skiing, hiking, and fishing. I’ve spent a lot of time outside. Unfortunately, the conditions for skiing are not quite the same where I live now, but I go running in nature a lot.” Sporty! “Sure, I’ve always been into different sports; for example, I played rugby for a long time. I stopped about four years ago when the pain in my body after a match or practice lingered a little too long. I’m guessing that has something to do with age.” Now that we’ve started talking about
A magazine from SciLifeLab
Photo: Mark Dopson
Mark Dopson and postdoc Margarita Lopez-Fernandez using a sampling device to collect and fix RNA from microbes living in groundwater.
Mine drainage stream, running along the side of a tunnel in the Boliden mine in Kristineberg, 250 meters below the surface. The acidophiles that Mark Dopson studies lives in the acid drainage. In the picture the microorganism’s biofilm appears as featherlike threads.
what microorganisms can actually contribute to, we come to the third area: acidophiles. Here, the team conducts basic and applied research. In this area, the extreme environment has a very low pH, which means the organisms have found ways to survive in acidic conditions. The basic research involves determining how
they are acid resistant and how they meet their energy needs in order to grow. What can we do with this information? “This is where the applied research comes in. Right now, we are gathering answers as to how the microorganisms’ metabolism functions; for example, ➔
Synergy #1 –– 2017
9
Photo: Curt-Robert Lindqvist
Reportage
Technology and service Mark Dopson’s group has used SciLifeLab’s genomics service to sequence organisms in all four projects. In the first project (about the deep biosphere in the Äspö Tunnel), they have used the center’s technology in single-cell genomics to reconstruct the genetic makeup of a number of individual bacteria from the deep biosphere. The single-cell methods allow them to analyze even the organisms that cannot be cultivated in the laboratory. The group has also used SciLifeLab’s bioinformatics service to analyze data.
In the Äspö Tunnel outside Oskarshamn, 450 m underground, Mark and his research group find many of the microorganisms they are studying.
“Your body actually consists of more cells from microorganisms than human cells.” we know they build a kind of biofilm to optimize their growth on mineral surfaces.” Oh yeah? “That’s right; take copper ore, for example: we can extract copper from ore by adding microorganisms with different properties that help release the metal. For example, by modifying them so that the biofilm is built much faster, we can optimize the extraction of copper. We hope to be able to build a model that explains this scenario to us. We need this information before we can conduct industrial tests.” But why is it important? “Look at this,” says Mark, and holds up his phone... “and your lovely computer. Our entire technological world is created from, among other things, copper. It is incredibly important to find environmen tally friendly procedures for extracting the metal; otherwise, we will continue with traditional extraction, which is causing environmental problems.” “Do you want to know another cool thing we can do for nature by understanding and using microorganisms?” asks Mark.
10
Synergy #1 –– 2017
Sure. “Now we’re in the fourth and final area, which for simplicity’s sake, I usually call a biobattery.” Mark explains that when they look at the metabolism of microorganisms, how they break down nutrients and create energy, researchers have discovered that they can use organisms by fooling them. “Explained simply, when we cut off the oxygen supply to an organism, we force it to find new ways to create energy. And this has proven, in some cases, to produce electricity.” The tests are being conducted on waste products from the mining industry, which involve tons of sulfur compounds. “Sulfur compounds are not something we want in nature; that’s why all water from industrial production is purified. So if we can get microorganisms to break down sulfuric acid and even create electricity, then we not only have a cost-effective way to protect the environment, but also an environmentally friendly process for creating electricity. The long-term goal is to be able to create a biobattery that
treats waste products in process waters, and for this to be used in industry. That way we can avoid the current purification process, which uses chemicals. And where are you now? “Right now, we are focusing on understanding and explaining the microorganisms’ system.” Mark clearly loves his job and naturally, I become curious about how microorganisms became such a big part of his life. The answer is David Attenborough, known for series like Life on Earth and The Living Planet. “I was around 10 or 12 when I saw Life on Earth for the first time. The sequence that really caught my attention was when volcanic gas streamed up from the sea floor. I remember how they talked about these newly discovered microorganisms, which lived in a chemical from the earth’s core. Microbiology has been with me ever since.” That sounds familiar. “I know; it’s kind of funny that I am investigating almost exactly the same thing that sparked my interest so many years ago.” “By the way, did you know that microorganisms are a large part of your life, too?” he asks after we’ve concluded the interview. How so? “Your body actually consists of more cells from microorganisms than human cells. Exciting, right?”
A magazine from SciLifeLab
Interview Text: Kristina Tilvemo / Photo: Mikael Wallerstedt
Is it possible to restore hearing? When one of his teachers developed hearing loss during his studies, he became interested in the ear and hearing – an interest that hasn’t diminished. Helge Rask-Andersen, senior professor in experimental otology, investigates the possibility of giving deaf people their hearing back. Eight months ago, he stopped his surgery practice. Today, he runs several parallel projects on cochlear implants and inner ear research. “Children who are born deaf can have their hearing restored with an electronic implant, and with the help of SciLifeLab’s technology, we are looking at the human inner ear and the protein expression in it. Half of these kids are born without one functioning protein, and for the last two years, we have been studying this protein with a super-resolution fluorescence microscope,” explains Helge Rask-Andersen, senior professor in experimental otology at the Department of Surgical Sciences, Ear, Nose and Throat Diseases, Uppsala University. Usually, sensory deafness is due to the inner ear lacking functioning hair cells, which convey sound impressions to the hearing nerve, where they are converted into electrical impulses. In other patients, there are also damages on the hearing nerve, which in some cases can be treated through a brainstem implant. “Hearing nerve damage is significantly more complex and we are currently the only country in the Nordic region to conduct brainstem implants. We perform surgery on a few patients per year and research the results. The procedure requires collaboration with neurosurgeons, and we also hold training courses in inner ear surgery for surgeons from all over the world,” explains Helge Rask-Andersen. He will soon travel to South Korea to share his experiences. The last twenty years have seen enormous progress, especially through the development of cochlear implants, concludes Helge Rask-Andersen. “I never thought I would get to see this day. We have had incredible clinical development and in Uppsala we have made many discoveries. Cochlear implants are originally from the US, France and Austria, but we have improved the technology in Sweden. Today, we are seeing excellent opportunities in the art of restoring hearing.”
A magazine from SciLifeLab
“Usually, sensory deafness is due to the inner ear lacking functioning hair cells.”
Technology and service Among other things, Helge Rask-Andersen’s group studies the molecular arrangement of the proteins connexin 26 and 30, which are important for hearing. For this work, they have used SciLifeLab’s image analysis service in the form of advanced high-resolution microscopy, especially SR-SIM. In order to refine their image analysis skills, they have also participated in courses arranged by SciLifeLab.
Synergy #1 –– 2017
11
On site Text: Anna Jansson / Photo: Mikael Wallerstedt
Digging for new breakthroughs What can we learn from the role of fungi in nature? Using brand new technology in ecological research, Björn Lindahl is seeking answers with one foot in the forest and the other in the lab.
Y
ou can look at it as a crime scene investigation,” says Björn Lindahl, professor of soil biology at the Swedish University of Agricultural Sciences (SLU). “We identify fungi with methods similar to those used when solving a suspected murder: with the help of DNA sequences.” Suddenly, I sense that ecological studies of fungi may be a little more engaging than the name suggests. Björn quickly explains that what I see as mushrooms are just a paltry fraction of the extensive community living underground. Thousands of species, right beneath my feet. Björn is interested in the role these species play in ecosystems, where some live in symbiosis with plants and some break down dead plant components. And we’re talking about relatively new discoveries. Research in this field really took off ten years ago, in conjunction with a number of technological breakthroughs. “Thanks to the new technology, a new field of research gained momentum: molecular ecology. You could say that lab technicians moved into the forest and countryside,” says Björn. In Björn’s field, a massive mapping of the large groups of
12
Synergy #1 –– 2017
organisms that live in places humans do not normally see, is underway. One of the purposes is to understand ecological connections in order to be able to help farmers, forest managers and decision-makers. “It’s not up to me to decide whether they will preserve a species, but they should know the consequences of their actions on the ecosystem,” concludes Björn. At the same time, he is clear about the research not becoming an endless survey process, and emphasizes the importance of maintaining a focus on basic scientific questions. “It’s important to use this new technology in a beneficial way and to learn to ignore data that doesn’t interest us. Because there are barely any limits to how much data we could collect.” He provides the following example: if we want to know why carbon is being lost from soil, then we have to look for genes in fungi that control the respiration of carbon dioxide. One of the most important questions for Björn right now is what determines how much carbon is stored in the soil. How are you figuring out the answer? “The process starts with collecting soil samples from a forest and then extracting DNA. You don't need much; we can really
“I make sure that I still have one foot in the forest.”
A magazine from SciLifeLab
Discovered Text: Peter Johansson / Photo: Mattias Pettersson
New method for treating rheumatoid arthritis capture the essence of the forest in a teeny, tiny drop. 50 micro liters, the equivalent of a single tear, can contain information about 30 huge forest areas in central Sweden.” He explains that they are using a genetic marker (ITS2) as a bar code for various fungi species. After sequencing, they have “hundreds of novels” worth of information, from a single study. “So you can understand that it’s important to know what we’re looking for,” Björn points out. After processing the data, they extract long species lists, where genetic data is transformed into biologically meaningful information. The method is now being further developed to also in clude mRNA. “In that case, we’re talking about genetic messenger molecules that transform the DNA code into proteins,” Björn clarifies. This approach produces information about what the species actually do, not just which ones exist. “This is where we see, for example, which species compost; which contribute nutrients to trees, and which live as parasites on different trees and other plants. Right now, we’re in the middle of scaling up the sequencing, which in practice means the quantity of information that used to correspond with hundreds of novels corresponds with millions instead. An entire school gym of books: that’s how much information we can squeeze out of that tear,” Björn explains. And he adds, “An infrastructure like SciLifeLab allows advanced technology to contribute within many more areas than medical biotechnology.” Molecular ecology is only one example. “Like I was saying before, I’m not talking about any automation; the inquisitive researcher is still the main ingredient in this process. Anyway, I make sure that I still have one foot in the forest.” Björn also emphasizes how young the methodology and technology are, and that the future holds plenty of answers if we can successfully increase our understanding of this huge group of organisms. “How else would we know what their potential significance is? Because it could very well reach beyond ecology; maybe a new antibiotic? I’m incredibly motivated by the unexpected benefit to which this type of study could lead.”
Technology and service Björn Lindahl’s research group has used SciLifeLab’s genomics service to sequence the fungi in the mapping process.
A magazine from SciLifeLab
When Susanne Lindquist and her research group discovered a connection between the protein BSSL and inflammation, the idea was born for a new drug, treating rheumatoid arthritis and similar conditions. Tests showed that the disease does not affect mice that are missing the BSSL-producing gene. The hunt for a new antibody began. After a long time of studies of the protein bile salt-stimulated lipase (BSSL), which is found in breast milk, Susanne Lindquist, Senior research engineer at Umeå University, discovered that the protein could also be found in conjunction with inflammation in the body. This was the beginning of tests, which showed that mice that cannot form the protein do not develop rheumatoid arthritis. “We have developed an antibody that binds the BSSL-protein and blocks its function. This means that we can alleviate or even prevent rheumatoid arthritis in animals,” says Susanne. With this discovery in their back pocket, Susanne and her group contacted SciLifeLab. Now they wanted to study whether they could use this new information about antibodies to develop a humanized antibody. And consequently, a medicine that works in humans. They had never developed a humanized antibody before and needed someone to partner with. A project group from SciLifeLab was appointed. The purpose of the research is to develop a medication with a new mechanism of action to treat children and adults with rheumatoid arthritis, as well as other diseases involving inflammation. There is currently no treatment available that specifically targets the BSSL protein. “The drugs that currently exist work really well for some patients but help far from everyone. In addition, the effects often subside in many people who were initially helped, often within a year, and they must therefore change treatments. We hope and believe that we can create an alternative for when the existing treatments don’t work. We know this is needed.” At the time of this writing, the team is well on its way to developing the humanized antibody. “During 2017, we will have an antibody that should be able to function in humans; then we have to conduct tests to ensure the treatment is safe and does the job,” finishes Susanne.
Technology and service Susanne Lindquist’s group is using SciLifeLab’s service in drug development to develop the humanized antibody.
Synergy Synergy##11 –– 2017
13
Portrait
To lead research is like running your own business
How do most people imagine a researcher? We asked Kristina Broliden, professor of infectious diseases at Karolinska Institutet in Stockholm, that question and it didn't take long before she responded: Text: Peter Johansson / Photo: Mikael Wallerstedt
14
Synergy #1 –– 2017
A magazine from SciLifeLab
Portrait
D
efinitely a man. His appearance may be replan is to begin corresponding studies in healthy subjects in 2018 miniscent of Albert Einstein. He’s also a little and then scale up to larger clinical studies. confused, socially awkward and a loner.” “We know that our drug candidate prevents HIV infection in We met Kristina Broliden at her office both cell cultures and animal studies. But with sexual contact, at Karolinska Institutet in Solna and were irritation to the mucous membranes of the genitals could increase quickly struck by the fact that she is incredibly the risk of transmission, which is why it is important to check that far from this biased image of a researcher. the cream does not have this side effect,” says Kristina Broliden. The office is welcoming, and Kristina shows The collaborating research groups’ initiatives also contribute to no signs of being either confused or socially awkward. Although vaccine research, but that is not the final goal of this project. Even one detail in the room stands out rather sharply: a Canadian team if this product does not go all the way to clinical use, the funder jersey on a hanger. believes the project will generate a lot of new fundamental inform “You have no idea how close I came to being forced to wear ation that can be used in the battle against HIV. Kristina Broliden that thing at a huge research convention in the US recently,” says is also leading another interesting project in Kenya. There, the Kristina Broliden. research group is studying why about five percent of a large cohort The background is a bet she entered with a Canadian colleaof female sex workers don't get infected with HIV, even though gue just before the 2016 World Cup of Hockey. there are hundreds of infections annually. The The likely scenario was that Sweden and Canada research group is taking samples from them and would face off in the final and if Canada won, comparing these with women who have HIV, to Kristina would have to wear Canada’s team jersey study what differences exist, for example genetic, to the convention while mingling with colleagues and how they impact sensitivity to infection. in suits and gowns. And vice versa if Sweden won. At the same time, they are studying how the The bet was over before it started when Sweden contraceptive shot impairs defenses against was ousted in the semifinal. HIV, that is, that the mucous membranes may Kristina developed an interest in ice hockey be weakened. The contraceptive shot, given four from her kids. Her daughter actually played tentimes per year, is a common birth control method nis, but both sons focused on ice hockey and one in low-income countries, but unfortunately a conThe Canadian jersey stands out sharply. It serves as a memory of them, Mikael, moved to the US to study and nection has been reported between the shot and of a fun and unusual bet. play in the junior league in St. Louis. increased vulnerability to HIV. Kristina is trying “I’ve probably seen every skating rink in the to figure out why. country, and even some outside of Sweden,” says Kristina. What is so incredible about conducting research? In brief, Kristina Broliden is just like any other parent. Almost. What’s the magic? There are a few differences. Kristina probably has more patience “It’s when you’ve rammed your head into the wall 99 times than most of us, and she is a leader. Her research work is highly and then suddenly... the hundredth time... you succeed. However, based on social competence, and leading research projects or there’s no fumbling in the dark; you read a lot of literature and groups requires leadership skills. “It’s like running your own scrutinize your hypotheses systematically and then shape your company, with budget work, staff responsibilities and external own projects.” contacts to manage.” Finally, Kristina, what do you hope to have achieved on Kristina Broliden combines her professorship with a position as the day you finish your research? senior physician at the Clinic of Infectious Diseases at Karolinska “I hope that we know which molecules govern the various University Hospital, Solna. She is also head of the Department of parts of the body’s battle against HIV infection, and that this will Medicine, Solna. She oversees 500 employees and is responsible have led us to a path for preventing infection, maybe in the form for an additional 400 KI-related individuals, in addition to her of an antiviral cream that is used before sexual activity, together own research group. And even if Kristina has not been seeing pawith a vaccine.” tients for about fifteen years, she is often consulted on tricky viral disease cases. This is an equation that requires something extra. “It’s all about knowledge, common sense and delegating. Kristina Broliden I also sleep well at night and quickly become re-energized,” Name: Kristina Broliden. says Kristina. Job: Professor of infectious diseases at Karolinska Institutet. Senior phy-
K
ristina has been researching HIV since the mid1980s. Today she leads a research group, which, together with nine other research groups globally, evaluates a preventive protein-based medication to combat the sexual transmission of HIV infection. The project attracted significant attention in fall 2014 when it was awarded a research grant of USD 14.7 million (approximately SEK 132 million with the current exchange rate). The medication, a cream, was developed by another research group. Kristina’s task is to rule out side effects of the cream in the form of irritation to the mucous membranes where it is active. “It’s an incredible opportunity and the grant is for five years, which feels especially great and gives us the time to really dive in deep. Grants are usually for three years,” says Kristina Broliden. The research group in the US has tested the cream in animal studies. With advanced molecular methods, Kristina’s group is comparing how the tissue looks before and after treatment. The
A magazine from SciLifeLab
sician at the Clinic of Infectious Diseases, Karolinska University Hospital, Solna. Head of the Department of Medicine, Solna. Family: Husband Jan and three children. Loves to read: Mysteries. Most recent vacation: A weekend spent skiing in Åre. We have an apartment there and go as often as we can, downhill, uphill and cross-country.
Technology and service In the two HIV projects, tissue biopsies of intestinal and vaginal mucous membranes will be analyzed using an image analysis program that is being developed together with SciLifeLab. In the sub-study on vulnerability to infection, Kristina Broliden’s group uses SciLifeLab’s proteomics services to measure the protein composition of study subjects’ genital secretions. By using the center’s diagnostics services they have measured the content of the natural bacteria in the mucous membrane of the vagina. In both projects, the research groups are working closely with SciLifeLab on project design and further development of applications that may provide solutions to clinical questions.
Synergy #1 –– 2017
15
Hello there! Text: Kristina Tilvemo / Photo: Mikael Wallerstedt
Mårten Fernö ... …whose research focuses on breast cancer and treatment sensitivity at the Division of Oncology and Pathology, Department of Clinical Sciences, Lund University.
You recently started a project on breast-conserving surgery. Tell us more! “This involves breast surgery in which only a portion, rather than the entire breast, is removed, and administering radiotherapy in order to reduce the risk of local recurrence. Because some patients will never develop local recurrence – and thus do not really need radiotherapy – while others develop recurrence despite radiotherapy, it is important to identify who can really benefit from the treatment. The material includes 45 patients, some of whom had radiation after surgery and others who did not. Our hope is that those who received radiation and still had a recurrence will have a certain DNA pattern that explains why their tumors are resistant to radiotherapy. We also hope to determine which cases are recurrences of the first breast cancer, so-called true local recurrence, and which are completely new primary tumors. Our hypothesis is that this will be significant for patient outcome. This is a collaborative project with several physicians in the country.” What do you want to show with your research? “That by measuring different properties of a tumor, you can improve the choice of treatment and thus the patient prognosis as well. You may think of breast cancer as one single disease, but it is actually many different variants. Encouragingly, about
16
Synergy #1 –– 2017
60 percent of the patients are cured already by the first surgery. Others have a more aggressive form and develop a recurrence after a few months. It is therefore important to identify the different groups, where patients with a gentler variant need little to no additional treatment, while patients with an aggressive variant must be treated, with individualized adjuvant therapy.” What does the general public not know about breast cancer? “I think they might think the prognosis is worse than it is. Over 8,000 women in Sweden develop breast cancer annually, but if you get that diagnosis and optimal treatment, chances are good that you will survive without a recurrence. This is an important message.”
Technologies and services In this project, Mårten Fernö’s research group used SciLifeLab’s genomics service for whole genome sequencing of nearly 100 breast cancer samples from 45 patients. The group has also received support from SciLifeLab’s bioinformatics services to analyze data from the project.
A magazine from SciLifeLab