KI News

Nearly 1,500 people spent their Saturday in Biomedicum, when Karolinska Institutet held an open house for the public. Visitors could attend exhibitions, activities and lectures with KI researchers in the newly opened laboratory and learn more about stem cells, physical activity, pain, intestinal flora and much more.

The Nobel Assembly at Karolinska Institutet has today decided to award the 2018 Nobel Prize in Physiology or Medicine jointly to James P. Allison and Tasuku Honjo for their discovery of cancer therapy by inhibition of negative immune regulation. Cancer kills millions of people every year and is one of humanity’s greatest health challenges. By stimulating the inherent ability of our immune system to attack tumor cells this year’s Nobel Laureates have established an entirely new principle for cancer therapy. James P. Allison studied a known protein that functions as a brake on the immune system. He realized the potential of releasing the brake and thereby unleashing our immune cells to attack tumors. He then developed this concept into a brand new approach for treating patients. In parallel, Tasuku Honjo discovered a protein on immune cells and, after careful exploration of its function, eventually revealed that it also operates as a brake, but with a different mechanism of action. Therapies based on his discovery proved to be strikingly effective in the fight against cancer. Allison and Honjo showed how different strategies for inhibiting the brakes on the immune system can be used in the treatment of cancer. The seminal discoveries by the two Laureates constitute a landmark in our fight against cancer. James P. Allison: Affiliation at the time of the award: University of Texas MD Anderson Cancer Center, Houston, TX, USA , Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA Prize motivation: ”for their discovery of cancer therapy by inhibition of negative immune regulation.” Prize share: 1/2 Tasuku Honjo: Affiliation at the time of the award: Kyoto University, Kyoto, Japan Prize motivation: ”for their discovery of cancer therapy by inhibition of negative immune regulation.” Prize share: 1/2

Obese mothers who lose weight through bariatric surgery can have safer deliveries. The positive effects are many, including fewer caesarean sections, infections, tears and haemorrhages, and fewer cases of post-term delivery or uterine inertia. This according to an observational study by researchers at Karolinska Institutet in Sweden published in PLOS Medicine. Today, more than one in every three women admitted into prenatal care are either obese or overweight, and statistics from the National Board of Health and Welfare show that this is a rising trend. “We know that obesity and overweight are dangerous in connection with childbirth,” says Dr Olof Stephansson, obstetrician and researcher at Karolinska Institutet’s Department of Medicine in Solna. “Bariatric surgery is by far your best option if you want a lasting weight reduction over time.” The research group to which he belongs has made several studies of how bariatric surgery affects pregnancy and childbirth. This latest study compared deliveries in 1,431 women who had achieved considerable weight loss after bariatric surgery, with those in 4,476 women who had not undergone surgery. The women in the control group had the same BMI during early pregnancy as the experimental group had had before surgery. Comparison was done using registries “The effects were quite salient, and all of those we studied were to the benefit of the women who’d had surgery,” says Dr Stephansson. “There are a lower proportion of C-sections, fewer induced deliveries, a lower proportion of post-term deliveries, less frequent epidurals and fewer cases of uterine inertia, infection, perineal tears and haemorrhaging.” The comparison was done using the Scandinavian Obesity Surgery Registry (SOReg) and the Medical Birth Registry. The positive effect is thought to be attributable to the considerable weight loss that these women have undergone, on average 38 kilos from the time of surgery to the start of pregnancy. At the same time, earlier studies show that women who have bariatric surgery run a slightly greater risk of pre-term delivery and having babies that are small for their gestational age. “It’s therefore not as simple as just advising every woman who’s overweight to have bariatric surgery,” says Dr Stephansson. “But going by the results of this study, it has positive effects for mothers. More studies are needed in which we weigh up outcomes so that we can give a more general recommendation.” Bariatric surgery number is rising The Swedish studies should also be complemented with similar studies in other countries, he says. Internationally, Sweden stands out in terms of the volume of bariatric surgery performed. “Today, one per cent of all babies born in Sweden have mothers who have had bariatric surgery. It might not sound many, but this number is rising. When the women start to lose weight their fertility quickly recovers, so this too is improved by the operation.” The research is patient-centred and conducted by people with different competencies, including obstetricians, nutritionists, surgeons and epidemiologists. “Thanks to the fact that we combine good study design and method with proximity to clinic and patient, we can also conduct really good studies,” says Olof Stephansson. The study was financed with grants from several bodies, including the Swedish Research Council for Health, Working Life and Welfare (FORTE), the Swedish Research Council, Karolinska Institutet and the National Institute of Diabetes and Digestive and Kidney Diseases. Publication  “Delivery outcomes in term births after bariatric surgery: Population-based matched cohort study”. Olof Stephansson, Kari Johansson, Jonas Söderling, Ingmar Näslund and Martin Neovius. PLOS Medicine, online 26 September 2018, doi: 10.1371/journal.pmed.1002656.

Hormone-disrupting chemicals in our environment can affect early neurodevelopment in children, but little is known about the exact mechanisms for this interference. A new EU funded research project, coordinated from Karolinska Institutet, now aims to learn more and to develop better screening and testing tools.     The project called ENDpoiNTs (Novel Testing Strategies for Endocrine Disruptors in the Context of Developmental NeuroToxicity) includes 16 partners in Europe, United States and Australia. Coordinator for the entire project is Dr Joëlle Rüegg, a molecular biologist and associate professor at the Institute of Environmental Medicine (IMM), Karolinska Institutet and also affiliated to the research organisation Swetox. The project is funded through the Horizon2020 framework programme with EUR 6.89 million or about SEK 70 million. The ENDpoiNTs researchers hope to clarify the causal link between hormone-disrupting chemicals and neurodevelopmental injuries by integrating expertise from different, but today largely independent, toxicology communities, and by combining novel experimental technologies with advanced biostatistics on human epidemiological and biomonitoring data. Another important aim is to ensure that the tools developed by the project can successfully be used in society.

That men who have sex with men run a greater risk of HIV than others has been known since the virus was discovered. However a thesis from Karolinska Institutet now shows that it is a small sub-group of these men who account for the greater part of the risk increase. The results are important to preventive efforts against HIV in Sweden. Men who have sex with men (MSM) are disproportionately affected by HIV compared to the general population, and now an increase in other sexually transmitted diseases, such as syphilis and gonorrhoea is also seen. The pattern is similar in large parts of Western Europe and North America. In her research, Kristina Ingemarsdotter-Persson has focused on how to distinguish groups of MSM with different risk profiles and preventive needs in order to better target preventive measures. Those who have many sexual partners and a broader sexual repertoire possibly require more and different kinds of intervention. Receptive for preventive measures “Men who have sex with men, particularly the high risk-takers, are open and receptive for preventive measures,” says Ms Ingemarsdotter-Persson, doctoral student at the Department of Public Health, Karolinska Institutet. “Healthcare providers need to utilise HIV test occasions and other contacts to reach these men with the right messages and offers.” Using both quantitative and qualitative methods, she has examined how Swedish MSM perceive and handle sexual risk-taking. “We found that those with high-risk behaviour often have it both at home and while traveling abroad. They also are better informed about HIV and sexual health than others. It was clear that for many of them, sex was important, but it was equally clear that they care about their own health and that of others.” Can live a long, healthy life In recent years, several studies have shown that someone living with HIV and who has effective medical treatment with undetectable virus levels can live a long, healthy life, and are not infectious when having sex. HIV rapid testing with results delivered within half an hour and prophylactic HIV treatment (PrEP, pre-exposure prophylaxis for HIV) are now made available for Swedish MSM. “Today, HIV should be seen as a chronic infection rather than a fatal disease,” Ms Ingemarsdotter-Persson says. “My research shows, unfortunately, that anxiety about being infected and unawareness about the rapid advances in HIV research still make some people not getting tested, even though the consequences of a positive result are completely different to what they once were. Knowledge about the HIV treatment progress needs to spread. Most importantly, however, we need to continue preventing HIV infection.” Kristina Ingemarsdotter-Persson is due to defend her thesis “Relating to risk: sexual behaviour and risk perception among men who have sex with men” at Karolinska Institutet on 28 September 2018.

The causes of the difficult-to-treat pain syndrome fibromyalgia are largely unknown. Using PET brain imaging, researchers at Karolinska Institutet and Harvard University have now shown that glial cells – the central nervous system’s immune cells – are activated in the brains of patients with fibromyalgia. The finding which is published in the scientific journal Brain, Behavior, and Immunity opens the way for new therapies. Fibromyalgia is a chronic pain syndrome that causes extensive pain in the muscles and joints, severe fatigue, insomnia and cognitive difficulties. The higher pain sensitivity that is characteristic of the syndrome has been related to functional and structural alterations of brain regions associated with pain processing. In 2012, Eva Kosek’s research group at Karolinska Institutet showed that patients with fibromyalgia had elevated levels of certain inflammatory substances (cytokines) in the cerebrospinal fluid, suggesting inflammation of the central nervous system. Their findings were subsequently corroborated by other researchers, but the source of the inflammation remained unknown. Glial cells are activated Using modern PET (positron-emission topography) brain imaging Eva Kosek’s team has now been able to show that the central nervous system’s immune cells, called glial cells, are activated and thus give rise to inflammation of the brain. “As far as we know, this is the first time it’s been shown that glial cells are involved in the pathogenesis of fibromyalgia,” says Professor Eva Kosek from the Department of Clinical Neuroscience, Karolinska Institutet. The results show that in Swedish and American patients with fibromyalgia, glial cells are activated in large parts of the cerebral cortex, and that the degree of activation was related to the degree of fatigue reported by the patients. Objective aberrations in the brain “The findings may open the way for the development of completely new therapies for this currently difficult-to-treat condition,” says Professor Kosek. “The fact that scientific research is able to demonstrate objective aberrations in the brains of people with fibromyalgia will hopefully mitigate the suspicion with which patients are often treated by the health services and society.” Today, an estimated 200,000 Swedes, mainly women, suffer from fibromyalgia. The brains of people with the condition are known to have an impaired ability to dampen pain signals, which means that things that are normally painless cause considerable discomfort. The study was a collaboration between Eva Kosek’s research group at Karolinska Institutet in Sweden, the PET Centre at Karolinska Institutet and Dr Marco Loggia’s research group at Harvard University, Cambridge, USA. The research in Sweden was financed from several sources, including the EU’s 7th Framework and Programme and a donation from the Lundblad Family. The Swedish part of the project was also funded by Stockholm County Council, the Swedish Research Council, the Swedish Rheumatism Association and the Swedish Fibromyalgia Association. Publication “Brain glial activation in fibromyalgia – A multi-site positron emission tomography investigation” Daniel S. Albrecht1, Anton Forsberg1, Angelica Sandström, Courtney Bergan, Diana Kadetoff, Ekaterina Protsenko, Jon Lampa, Yvonne C. Lee, Caroline Olgart Höglund, Ciprian Catana, Simon Cervenka, Oluwaseun Akeju, Mats Lekander, George Cohen, Christer Halldin, Norman Taylor, Minhae Kim, Jacob M. Hooker, Robert R. Edwards, Vitaly Napadow, Eva Kosek2, Marco L. Loggia2 1Co-first authors, 2Co-senior authors Brain, Behavior, and Immunity, online 14 September 2018, doi: 10.1016/j.bbi.2018.09.018

Researchers from Karolinska Institutet and Kancera AB have developed a molecule that makes cancer cells sensitive to radiotherapy. In a study published in Nature Communications, the researchers describe a new way to block cancer cells' ability to repair their DNA and thus stop the survival of cancer cells. Radiotherapy is one of the most common cancer treatments. It damages the DNA, causing cancer cells to stop growing and die if the damage is left unrepaired. Unfortunately, some cancers are resistant to radiotherapy and the treatment also damages the DNA in healthy cells, thus limiting the amount of radiation that can be used with respect to normal tissue damage. In collaboration with the Swedish company Kancera AB, researchers at Karolinska Institutet have discovered a new mechanism that cancer cells use to repair DNA damage. In the current study, the researchers discovered that cancer cells use a protein called PFKFB3 to repair the DNA damage that occurs in radiation therapy. They found that the protein locates to sites of DNA damage in the cell nucleus where the protein regulates the cancer cell's ability to repair its DNA and thus survive. Drug candidate blocks the protein The research groups at Kancera AB and Karolinska Institutet have now developed a new drug candidate which blocks the protein and its ability to repair DNA damage. They demonstrated that cancer cells treated with the drug do not survive upon radiotherapy in laboratory experiments. “It is known that the levels of PFKFB3 is much higher in cancer cells than in healthy cells. However, the discovery that PFKFB3 regulates DNA repair upon radiotherapy is new and very exciting,” says Nina Gustafsson, Assistant Professor and Team Leader in Translational Medicine at the Department of Oncology-Pathology, Karolinska Institutet, who led the study together with Professor Thomas Helleday at the same department. Foundation for a new cancer treatment Since normal, healthy cells are not dependent on PFKFB3 for proper DNA repair, the researchers hope that combination therapy with radiation or chemotherapy will be well tolerated. The goal is now to further develop the drug and lay the foundation for a new cancer treatment with less side effects than the treatments currently available. The study was led by researchers at Karolinska Institutet, operating at SciLifeLab, and Kancera AB, and in collaboration with researchers from Stockholm University, University of Sheffield, Sprint Bioscience, Roma Tre University, Emory University School of Medicine and more. The research has been funded by the Swedish Society for Medical Research, the European Union's Horizon 2020 research and innovation program, together with Torsten Söderberg and Ragnar Söderberg Foundation and more. Publication ”Targeting PFKFB3 radiosensitizes cancer cells and suppresses homologous recombination”. Nina M.S. Gustafsson, Katarina Färnegårdh, Nadilly Bonagas, Anna Huguet Ninou, Petra Groth, Elisee Wiita, Mattias Jönsson, Kenth Hallberg, Jemina Lehto, Rosa Pennisi, Jessica Martinsson, Carina Norström, Jessica Hollers, Johan Schultz, Martin Andersson, Natalia Markova, Petra Marttila, Baek Kim, Martin Norin, Thomas Olin, Thomas Helleday. Nature Communications, online 24 September 2018, doi: 10.1038/s41467-018-06287-x.

On Saturday 29 September Karolinska Institutet invites the general public to an open house at the newly opened research laboratory Biomedicum on Campus Solna. Visitors will get a chance to meet researchers during lectures, exhibitions, interactive activities, scientific activities for children and more. Hi there, Lilian Kisiswa, project leader and postdoc ... why is KI arranging an open house at Biomedicum? "KI organizes this open house because it's important to have an open and vibrant dialogue between researchers and the general public, and we want to give people a chance to find out about the high quality research conducted in the house. I'm very proud of KI, and research is a cornerstone of modern society and the two cannot be separated." What’s on the agenda for the day? "A lot! We’re offering classic lectures, interactive activities, exhibitions and a chance to look at our exciting laboratories and the building’s architecture. People will also get to ask questions direct to the researchers." Who is the open house for? "The event is free and for the general public, with or without an academic background, and there’s something for people of all ages." What’s special about the Biomedicum research building? "Biomedicum is an exciting, modern laboratory to work in and gives us researchers the chance to interact and collaborate. We can also share experiences, ideas and techniques across scientific boundaries, which is vital to research." What are you particularly looking forward to during the event? "We have a fantastic programme and I’ll try to attend all sessions. But if I had to choose one thing, then I’m looking forward to the interactive activities. As a visitor, you’ll get up close to research in an informal atmosphere. From our perspective, this will enable us to show how exciting research can be on an everyday basis and what it means to work as a researcher. To me, it’s a win-win situation."  

The anatomy of the head was the theme of KI president Ole Petter Ottersen’s first lecture for the university’s students last week. “I get inspired by lecturing and meeting the students,” he says. An important signal about what teaching means, according to Lena Nilsson-Wikmar, chair of KI’s pedagogical committee. The lecture is due to start, and the buzz in KI Campus Solna’s gradually filling Berzelius lecture hall is getting louder. At the front, Karolinska Institutet president Ole Petter Ottersen makes himself ready to hold his lecture on the anatomy of the head for students on the third semester of the medical programme. “I get inspired by lecturing and meeting the students, both as a lecture and a researcher,” he says. “The questions they ask often give me new ideas about and for my own research.” Once he has been introduced by Hugo Zeberg, physician and lecturer in anatomy at the Department of Neuroscience he turns to address the students: “It’s an honour to teach anatomy at Karolinska Institutet – so this is a big day for me.” He then opens the lecture with a picture of the human cranium. “The head and face are packed with different organs, so that a disease in one can easily affect another. To understand this, you must know your anatomy. My very first patient had a sinus infection the cause of which I wouldn’t have seen without such knowledge. But more about that later,” says Professor Ottersen. Invaluable signal having the president teach According to Lena Nilsson-Wikmar, professor of physiotherapy at the Department of Neurobiology, Care Sciences and Society and chair of KI’s Pedagogical Academy , having the president teach sends out an invaluable signal. “It shows that he thinks teaching is important. That the university’s educational mission, and not just its research, is actually incredibly important. If KI’s study programmes and courses are to be even more rooted in research, teaching must not only be done by lecturers but also by professors. That’s not always the case today, so he’s setting a good and vital example,” she says. After long having a subordinate role at KI, Professor Nilsson-Wikmar feels that teaching and education have recently taken on a greater prominence – even if the change is a slow one. She is pleased that these days, since the introduction of the new employment regulations in April, the positions of professor, senior lecturer and lecturer at KI require a ten-week training in academic pedagogy. But the course must not be something that people take for its own sake, she stresses. “If you’ve taken a course on student-centred learning, you have to actually apply it to your teaching. I hope this will be the case, and in that sense the president and those who lead educational activities here at KI present important role models,” she says. An incentive and a requirement for senior researchers to teach Professor Nilsson-Wikmar also thinks that there has to be both an incentive and a requirement for senior researchers to teach, and would eventually like to see more stringent demands on teaching hours when new appointments are made. Professor Nilsson-Wikmar also welcomes the newly established Unit for Education and Learning, of which she is the pro tem director. The idea of the unit is to gather together the university’s pedagogical activities and develop its pedagogical training. In the Solna lecture hall, Professor Ottersen shows a CAT scan of a patient’s head. He asks the students what the picture shows and receives a swift response. An inflammation in a sinus turns out to come from the root of a tooth. “Knowledge of anatomy is vital to understanding how diseases can develop in the patients you’ll be encountering,” he says. "Teaching with a real-life perspective" We break for coffee . In the fourth row sits medical student Marika Rostvall. She is enjoying the lecture, and particularly likes the links he makes to the clinical significance of anatomy. “I often find anatomy boring, learning all those names,” she admits. “But when I feel that I’ll have use for it, it’s more interesting to learn about.” She also thinks it’s good for the president to hold lectures, not only so that the students get to form an impression of him, but also so that he can see how the teaching works. “It sends the signal that he cares about us and about education and not only about the ones who do research or securing their financing,” says Ms Rostvall. Her course-mate Richard Wang is also pleased with the lecturer, whose approach he finds different to that of others. “He reflected a lot on what the anatomy actually looks like, like how thin some things are or how closely together they sit,” he says. “I love that kind of teaching, as textbooks don’t give you that kind of real-life perspective. It’s also great to see the university’s top executives being so engaged in the students.” Professor Ottersen is happy that the students participated so actively in the lecture. The break is soon over and he readies himself for part two. “Teaching is a fascinating and important job for everyone in a scientific position at KI,” he says. “It’s a vital aspect of our work. There are synergies to be gained from linking research to education and it’s the idea of a university to do just that.”

Muscle relaxants that are used during general anaesthesia increase the risk of pulmonary complications after surgery, according to the European multicentre study POPULAR, in which Karolinska Institutet researchers are involved. The study is published in the journal Lancet Respiratory Medicine. Increasing numbers of people around the world undergo anaesthesia and surgery, and in Sweden over 10 per cent of the population are exposed to anaesthesia every year. In the case of general anaesthesia, in order to reduce the dose of the anaesthetic and morphine-like drugs, so-called neuromuscular blockers are often also administered, thus mitigating the risk of complications. Even if this group of anaesthetic drugs has contributed to safer and more effective anaesthesia, several patient studies and smaller studies on healthy participants indicate that the addition of neuromuscular blockers to anaesthesia increase the risk of respiratory complications. In the current study, the researchers sought to ascertain if the use of these muscle relaxants in combination with anaesthesia and surgery increases the risk of developing post-surgical pulmonary complications, such as infections, respiratory insufficiency or lung collapse. Large European study Data from over 22,800 patients in 28 European countries who had received general anaesthetic, including some 1,200 patients from ten Swedish hospitals, were gathered from between July 2014 to April 2015. “The study shows that the use of neuromuscular blockers significantly increases the risk of pulmonary complications after anaesthesia and surgery,” says Malin Jonsson Fagerlund, consultant and docent at the Department of Physiology and Pharmacology, Karolinska Institutet. “More targeted studies need to be made to find out the underlying mechanisms behind this finding.” The study also shows that neither neuromuscular monitoring nor the use of drugs that reverse the neuromuscular blockade reduce the risk of post-surgical pulmonary complications. The study was financed by the European Society of Anaesthesiology. Publication “Post-anaesthesia Pulmonary Complications after Use of Muscle Relaxants: A Prospective Multicentre Observational Study (POPULAR)” Kirmeier E, Eriksson LI, Lewald H, Jonsson Fagerlund M, Hoeft A, Hollmann M, Meistelman C, Hunter JM, Ulm K, Blobner M and the POPULAR Contributors Lancet Respiratory Medicine, online 14 September 2018, doi: 10.1016/S2213-2600(18)30294-7

The bacteria Pseudomonas aeruginosa can cause serious and difficult to treat infections. The infection process involves the activation of toxic substances from the bacteria by a common protein in our cells. Researchers at Karolinska Institutet now show how this happens and that the activation can be stopped with drug-like molecules. The results are presented in Nature Communications. Pseudomonas aeruginosa infections are a common problem in hospitals. Antibiotic-resistant strains of the bacteria can cause life-threatening infections in patients with reduced immunity or large, open wounds. The bacteria also cause infection of the airways, which makes people with respiratory impairment, such as cystic fibrosis, particularly vulnerable. To find new means of treating these infections, researchers at Karolinska Institutet, Umeå University and Yale University have mapped the three-dimensional structure of two toxic proteins that the bacteria use to trigger the infection process. Protected by human protein The researchers have determined the structure of these toxins, called ExoS and ExoT, along with a human protein, called 14-3-3, which is known to be necessary for the toxins to become active. Previously, only little was known of the structure of one of the toxins (ExoS) and how it binds to the human protein. But it was unclear how this contact could give rise to the bacterium’s toxic effects. The team has now found a large, hydrophobic contact interface between the human protein and the bacterial toxins and shown that if this surface is not protected by the human protein, the toxins form inactive clusters in the cell’s water-soluble environment. In other words, the protein makes the bacterial toxins active by acting as a protective “chaperone”. A step towards new anti-infectives This newly identified contact interface presents a possible target for drug molecules. The study identified two small organic molecules that can prevent the infection between the bacterial toxins and the human protein. It also shows that the toxins lose their toxic activity when these molecules are introduced. The effect is weak, but according to the researchers, the results show that the principle works. The previously known contact between the bacterial toxins and the human protein takes place in an area where many other proteins in the cell bind. Affecting this region with drug molecules would probably therefore cause serious adverse effects. The newly discovered surface can prove a more specific target. “Our study shows that it’s possible to block toxin activity with drug-like molecules via an interface where no other proteins have yet been shown to interact,” says principal investigator Herwig Schüler, associate professor of structure biology at the Department of Biosciences and Nutrition, Karolinska Institutet. The study was financed by the Swedish Research Council, The Swedish Foundation for Strategic Research, the Wenner-Gren Foundation and the IngaBritt and Arne Lundberg Research Foundation. Publication “14-3-3 proteins activate Pseudomonas exotoxins-S and -T by chaperoning a hydrophobic surface” Tobias Karlberg, Peter Hornyak, Ana Filipa Pinto, Stefina Milanova, Mahsa Ebrahimi, Mikael Lindberg, Nikolai Püllen, Axel Nordström, Elinor Löverli, Rémi Caraballo, Emily V. Wong, Katja Näreoja, Ann-Gerd Thorsell, Mikael Elofsson, Enrique M. De La Cruz, Camilla Björkegren and Herwig Schüler Nature Communications, online 17 September 2018, doi: 10.1038/s41467-018-06194-1

Researchers at Karolinska Institutet have identified four types of neurons in the peripheral auditory system, three of which are new to science. The analysis of these cells can lead to new therapies for various kinds of hearing disorders, such as tinnitus and age-related hearing loss. The study is published in Nature Communications. When sound reaches the inner ear, it is converted into electrical signals that are relayed to the brain via the ear’s nerve cells in cochlea. Previously, most of these cells were considered to be of two types: type 1 and type 2 neurons, type 1 transmitting most of the auditory information. A new study by scientists at Karolinska Institutet shows that the type 1 cells actually comprise three very different cell types, which tallies with earlier research showing variations in the electrical properties and sonic response of type 1 cells. Three different routes “We now know that there are three different routes into the central auditory system, instead of just one,” says François Lallemend, research group leader at the Department of Neuroscience, Karolinska Institutet, who led the study. “This makes us better placed to understand the part played by the different neurons in hearing. We’ve also mapped out which genes are active in the individual cell types.” The team conducted their study on mice using the relatively new technique of single-cell RNA sequencing. The result is a catalogue of the genes expressed in the nerve cells, which can give scientists a solid foundation for better understanding the auditory system as well as for devising new therapies and drugs. “Our study can open the way for the development of genetic tools that can be used for new treatments for different kinds of hearing disorders, such as tinnitus,” says Dr Lallemend. “Our mapping can also give rise to different ways of influencing the function of individual nerve cells in the body.” Crucial function The study shows that these three neuron types probably play a part in the decoding of sonic intensity (i.e. volume), a function that is crucial during conversations in a loud environment, which rely on the ability to filter out the background noise. This property is also important in different forms of hearing disorders, such as tinnitus or hyperacusis (oversensitivity to sound). “Once we know which neurons cause hyperacusis we’ll be able to start investigating new therapies to protect or repair them,” explains Dr Lallemend. “The next step is to show what effect these individual nerve cells have on the auditory system, which can lead to the development of better auditory aids such as cochlear implants.” The researchers have also shown through comparative studies on adult mice that these different types of neurons are already present at birth. The study was financed by grants from the Swedish Research Council, the Knut and Alice Wallenberg Foundation (Wallenberg Academy Fellow), the Swedish Brain Fund, Karolinska Institutet, the Ragnar Söderberg Foundation and the Silent School Foundation. Publication ”Neuronal heterogeneity and stereotyped connectivity in the auditory afferent system” Charles Petitpré, Haohao Wu, Anil Sharma, Anna Tokarska, Paula Fontanet, Yiqiao Wang, Françoise Helmbacher, Kevin Yackle, Gilad Silberberg, Saida Hadjab and François Lallemend Nature Communications, online 12 September 2018

In multiple sclerosis (MS), not only the T cells of the immune system, but also its B cells, play an important role. This is shown by researchers at Karolinska Institutet and the University of Zurich in a study published in the journal Cell. The findings explain how a new class of MS drugs works, and can open up for more precise ways of treating the disease. MS is a chronic disease where the body's immune cells attack and damage its own nerve tissue. The disease affects around 2.5 million people worldwide, with a higher risk among women. Now, a key aspect in the development of the disease has been found by researchers at Karolinska Institutet and the University of Zurich. The results are published in the journal Cell. Faiez Al Nimer, researcher at the Department of Clinical Neuroscience at KI, is co-first author of the study. Attack the nerve cells Until recently, MS research has mainly focused on a type of immune cells called T cells. They normally help protecting the body against intruders. In some people, however, they attack the protective layer surrounding the nerve cells – marking the onset of MS. The new study shows that not only T cells, but also B cells of the immune system, play a role in the development of the disease, by activating the T cells. By analysing blood samples, the researchers saw that blood from people with MS contained increased numbers and activation status of T cells known to be important for MS disease activity.  When the B cells were eliminated, the activation status of these disease-driving T cells returned to normal, suggesting that B cells play a crucial role in the activation of autoimmune T cells in MS. Migrate to the brain The team also discovered that these activated T cells detectable in the blood notably included those that also occur in the brain in MS patients during flare-ups of the disease. These T cells were shown to recognise the structures of a protein that is produced by the B cells as well as nerve cells in the brain. The researchers conclude that after being activated in the blood by B cells, the T-cells migrate to the brain, where they destroy the nerve tissue. The study explains the previously unclear mechanism of a new class of MS drugs (rituximab and ocrelizumab) and can, according to researchers, pave the way for more precise ways of treating MS in the future. The research is funded mainly by the European Research Council (ERC Advanced Grant). Further funds come from the University of Zurich, the Swiss Multiple Sclerosis Society, the Swiss National Science Foundation and a number of Swedish funding sources. This news article is based on a press release from the University of Zurich. Publication "Memory B Cells Activate Brain-Homing, Autoreactive CD4 + T Cells in Multiple Sclerosis" Ivan Jelcic, Faiez Al Nimer, Jian Wang, Verena Lentsch, Raquel Planas, Ilijas Jelcic, Aleksandar Madjovski, Sabrina Ruhrmann, Wolfgang Faigle, Katrin Frauenknecht Clemencia Pinilla, Radleigh Santos, Christian Hammer, Yaneth Ortiz, Lennart Opitz, Hans Grönlund, Gerhard Rogler, Onur Boyman, Richard Reynolds, Andreas Lutterotti, Mohsen Khademi, Tomas Olsson, Fredrik Piehl, Mireia Sospedra, and Roland Martin Cell, online 30 August 2018, doi: 10.1016 / j.cell.2018.08.011

France’s Institut Pasteur’s ethical committee has cleared Karolinska Institutet’s President Ole Petter Ottersen from all suspicions of scientific misconduct, committee chairperson François Rougeon has announced on the conclusion of the investigation. On 19 July this year Karolinska Institutet received a complaint of suspected scientific misconduct against its president, Ole Petter Ottersen. The complaint concerned a scientific paper published in the Journal of Neuroscience almost twenty years ago (1999), of which Professor Ottersen listed as co-author. The case aroused considerable attention in the Swedish and Norwegian media, which connected it with the misconduct verdict that the President announced on 25 June 2018 concerning the so-called Macchiarini affair. The research on which the Journal of Neuroscience article is based was not conducted at KI, which means that the matter cannot be investigated here. The complaint was therefore dismissed. KI contacted the research principal, the Institut Pasteur in Paris, to check if they had considered the article in question and found it to qualify as scientific misconduct. On 5 September 2018, François Rougeon, chairperson of the Institut Pasteur’s ethical committee announced that, following a review of the data published in the article, the investigators found no grounds to bring a verdict of scientific misconduct: ”In our opinion, the analyses of the data does not support the allegation of scientific misconduct”.

Laura Fratiglioni, Håkan Eriksson and Bertil Fredholm are awarded Karolinska Institutet’s Grand Silver Medal 2018. They are given the medal for their great contributions to support KI’s activities. Since 2010, Karolinska Institutet awards medals to people who have made special contributions to support KI. Now this years recipients of the Grand Silver Medal are announced: Laura Fratiglioni, professor, Department of Neurobiology, Care Sciences and Society, KI Laura Fratiglioni is one of the leading international researchers in epidemiology of aging. She is awarded the medal for her outstanding contributions to Karolinska Institutet in science, doctoral education and leadership and innovation. With her strong clinical and scientific background, Laura Fratiglioni is often sought out as an expert in aging and she has strongly contributed to the international profile of KI in this field. Her work has contributed to the use of epidemiologic methods in agin research. Thereto, Laura Fratiglioni is devoted to communicating her research findings to the general public. Bertil Fredholm, professor emeritus, Department of Physiology and Pharmacology, KI Bertil Fredholm is awarded for his outstanding contributions to research and doctoral education in the area of pharmacology. Bertil Fredholm is one of KI’s most internationally acclaimed researchers. His discoveries are related to the molecule adenosine and its receptors, and he was among the first to describe ways in which caffein affects the body. Bertil Fredholm has been a member of the Nobel Committee for eighteen years, including two as its chairperson. He has also devoted a great deal of time to teaching, and was a highly regarded teacher at bot the undergraduate and doctoral levels. Håkan Eriksson, professor emeritus, Department of Women’s and Children’s Health, KI Håkan Eriksson is awarded the medal for his exceptional contributions to KI and to Swedish medical research. Håkan Eriksson is distinguished by a strong and innovative research career within reproduction biology, but also his extensive contributions to KI and to Swedish research policy. For fifteen years he was the Director of Studies at the Department of Medical Chemistry, and a driving force behind efforts to strengthen the clinical connection of the education. His work was of crucial importance, particular during the 1990s, when KI underwent a period of great change. The result of these changes included more efficient processes and higher quality research, education and collaboration throughout KI. The medals will be awarded in conjunction with the installation ceremony in Aula Medica in October.

In recent years access to drugs and vaccines has been increasing in many African countries, but the systems for monitoring treatment effects and reporting side-effects require further development. Karolinska Institutet will now lead an international collaboration project on pharmacovigilance – drugs safety – in four countries in East Africa. Those taking part in the project, known as PROFORMA, are researchers from Karolinska Institutet, researchers and experts from universities and regulatory authorities in Ethiopia, Kenya, Tanzania and Rwanda, and some regional and international stakeholders in the field of drugs safety. The total project funding is EUR 6 million, of which the major part is provided by the EU Framework Programme for Research and Innovation-Horizon2020, via the European and Developing Countries Clinical Trials Partnership (EDCTP). Among other significant funding bodies is the Swedish International Development Cooperation Agency (SIDA).  “The main aim of this project is to strengthen the national infrastructures for drugs safety monitoring in our partner countries in Africa. This involves developing regulatory capacity for routine surveillance and reporting, and training of staff working in healthcare and medical services and regulatory authorities,” says Dr Eleni Aklillu, senior researcher at the Department of Laboratory Medicine at Karolinska Institutet and scientific coordinator for the project. Right now, she is in Ethiopia attending the national kick-off meeting for PROFORMA. PROFORMA is estimated to last five years. The project also involve training at Master’s and postgraduate level and exchange of knowledge in general between researchers and experts. “The increasing number of clinical trials and different types of mass drug administration and vaccination programmes in African countries underlines the need to strengthen pharmacovigilance infrastructure. One important tool is to improve collaboration between the Medical Universities and regulatory authorities in the countries concerned, and we’ve already made good progress in this area during the few months we’ve been working on the project,” says Eleni Aklillu. Facts about PROFORMA Project title: Pharmacovigilance infrastructure and post-marketing surveillance system capacity building for regional medicine regulatory harmonization in East Africa (PROFORMA) Project funding: EUR 6 million, to be spread over five years, of which approx EUR 3 million will be funded by Horizon2020/EDCTP. Other funding bodies are SIDA, Karolinska Institutet, the Pharmacy and Poisons Board (Kenya), Muhimbili University of Health and Allied Sciences (Tanzania) and the Tanzania Food and Drugs Authority. Project period: 1 March 2018 – 28 February 2023 (60 months) Coordinator: Dr Eleni Aklillu, Associate Professor, Karolinska Institutet.  Website: proforma.ki.se

In both ADHD and emotional instability disorders (e.g. borderline and antisocial personality disorder as well as conduct disorder in children), the brain exhibits similar changes in overlapping areas, meaning that the two types of conditions should be seen as related and attention should be paid to both during diagnosis. This according to researchers at Karolinska Institutet behind a new study published in Molecular Psychiatry. The results can lead to a broader treatment for both conditions. Clinical attention has long been paid to the fact that individuals with ADHD also demonstrate emotional problems, such as chaotic emotional responses, anxiety and depression. Yet the relationship between ADHD and impaired emotional regulation has not been identified, even if theories have been proposed that both conditions are rooted in a dysfunction in how the brain controls its information processing. A new study by researchers at Karolinska Institutet in Sweden substantiated the hypothesis by showing how both ADHD and a form of emotional instability trait (conduct disorder trait in children) exhibit similar, overlapping changes in the brain. The study included more than 1 000 adolescents. Sibling conditions “We can call them sibling conditions, since they both involve partly overlapping underlying brain mechanisms, and therefore attention should be paid to both dimensions during diagnosis,” says Predrag Petrovic, associate professor at the Department of Clinical Neuroscience at Karolinska Institutet and consultant psychiatrist at North Stockholm Psychiatry. It was with the help of structural brain imagery (MR) that the team was able to show how both ADHD and conduct disorder traits in adolescents manifested themselves in the form of reduced brain volume and surface area in parts of the frontal lobe and nearby regions. The affected parts of the brain were generally overlapping, but the researchers also found changes that were specifically related to ADHD symptoms or symptoms seen in conduct disorder. The study also included behavioural experiments that demonstrated both conditions. “These results are important not least for the patients with emotional instability, since in many cases they are treated with scepticism and feel frustrated at not being taken seriously,” says Dr Petrovic. “We now show that this is related to changes in the brain that resemble those that have been observed in patients with ADHD, which can lead to a broader understanding and better diagnosis.” Broader treatment The study was part of the IMAGEN-project, an EU-funded collaboration amongst several European countries that aims towards a better understanding of how the brain and behaviour develop. The hope is that the study will not only lead to better diagnoses but also to better treatments, where people with an ADHD diagnosis can receive special therapy to help them better handle their emotions. “We also need to do more research to understand if central stimulant medication used for ADHD can also produce positive results for people with emotional instability disorders,” says Dr Petrovic. The study was financed with grants from several bodies, including the European Commission, the Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning (Formas), the Swedish Research Council, the National Institute for Health Research (NIHR), the Bundesministerium für Bildung und Forschung, the Swedish Society for Medical Research (SSMF) and Karolinska Institutet. Publication “Distinct brain structure and behavior related to ADHD and conduct disorder traits” Frida Bayard, Charlotte Nymberg Thunell, Christoph Abé, Rita Almeida, Tobias Banaschewski, Gareth Barker, Arun L. W. Bokde, Uli Bromberg, Christian Büchel, Erin Burke Quinlan, Sylvane Desrivières, Herta Flor, Vincent Frouin, Hugh Garavan, Penny Gowland, Andreas Heinz, Bernd Ittermann, Jean-Luc Martinot, Marie-Laure Paillère Martinot, Frauke Nees, Dimitri Papadopoulos Orfanos, Tomáš Paus, Luise Poustka, Patricia Conrod, Argyris Stringaris, Maren Struve, Jani Penttilä, Viola Kappel, Yvonne Grimmer, Tahmine Fadai, Betteke van Noort, Michael N. Smolka, Nora C. Vetter, Henrik Walter, Robert Whelan, Gunter Schumann and Predrag Petrovic. Molecular Psychiatry, online 14 August 2018, doi: 10.1038/s41380-018-0202-6

Professor Lorelei Lingard is awarded the 2018 Karolinska Institutet Prize for Research in Medical Education. Her research has contributed significantly to our understanding of how healthcare professionals interact and communicate with each other, which has led to new clinical practices and increased patient safety. Professor Lingard, Professor in the Department of Medicine at the Schulich School of Medicine & Dentistry and cross-appointed in the Faculty of Education at Western University in Canada, will receive the award and a prize amount of €50,000 at a ceremony in Stockholm, Sweden, on 11 October. This international prize is awarded for outstanding research in medical education. The purpose of the prize is to recognise and stimulate high-quality research in the field and to promote long-term improvements of educational practices in medical training. "Medical" includes all education and training for any health science profession. The prize is made possible through financial support from the Gunnar Höglund and Anna-Stina Malmborg Foundation. It is currently awarded every second year. Significant contributions “I’m happy to announce Professor Lingard as this year’s prize winner. She has contributed significantly to our understanding of how healthcare teams interact and communicate. Her research has been a major force in changing the way medical education views teamwork and has led to new clinical practices and increased patient safety,” says Professor Sari Ponzer, Chair of the Prize Committee. Since the late 1990s, Professor Lingard has been studying how healthcare teams function – both in providing patient care and during clinical training. She and her research team have studied expert and novice team members in settings as diverse as the operating room, the critical care unit, the heart function clinic, the organ transplantation team, the rehabilitation hospital, and the inpatient medicine ward. Communication is fundamental “My entry point into teamwork is always language. I’m interested in how teams communicate, because their communication is fundamental to how they collaborate and how they educate. My disciplinary training is in rhetoric – the study of how language works in social situations. Applying rhetoric to healthcare, I have worked to unravel what language does on teams. My research asks: what does language make possible in a team, and what does it constrain? As it turns out, language does many things that are critical for medical education and for care delivery. As a consequence of my research, we now pay systematic and critical attention to how clinical team members communicate with each other,” says Professor Lingard. My entry point into teamwork is always language. Her research has helped shape medical education policy in her native Canada as well as internationally. As a result, the role of language is today emphasised in clinical training, which was not previously the case. Her research has also inspired the recognition that teamwork is essential to how trainees learn. As clinical teams are the setting for most workplace-based learning in medicine, their structures and practices have a profound influence on that learning. Just a few decades ago, teamwork was not seen as important within medical education but today, thanks to Professor Lingard’s collaborative research programme, it’s recognised as a critically important aspect of what and how medical trainees learn. I’m very proud to be the first woman to win this prestigious prize Commenting on her Prize win, Professor Lingard says: “I’m deeply honoured to be recognised for this prize. Professionally, it’s a huge recognition of the work that I do together with my wonderful collaborative research teams, and the impact it has had. The field of team communication research didn’t exist 20 years ago and I’m enormously proud to have contributed to its development in our medical education community. From a more personal perspective, I’m very proud to be the first woman to win this prestigious prize.”    

Microvascular dysfunction, or small vessel disease, can be an important cause of heart failure with preserved ejection fraction (preserved pumping capacity), an international team including researchers from Karolinska Institutet and AstraZeneca report in a study published in The European Heart Journal. The results can play a crucial part in identifying people in the risk zone for this type of heart failure and in the development of effective drugs. Heart failure is the most common reason for hospitalisation and causes much suffering. Heart failure with preserved ejection fraction, which is one of the two main types of heart failure, lacks scientifically proven treatments and more research is needed to understand how the disease develops and is to be treated. Scientists at Karolinska Institutet, along with colleagues from AstraZeneca and four other groups in Sweden, the USA, Finland and Singapore have now conducted a study of over 200 patients with this type of heart failure. An innovative coronary imaging protocol developed The study involved the use of an innovative coronary imaging protocol developed by Professor Li-Ming Gan’s research group in the IMED Biotech Unit in order to obtain a patient-friendly, cost-effective way to test coronary artery’s ability to increase its blood flow (Coronary Flow Reserve - CFR) in addition to the traditional imaging approach to generate overall picture of the heart’s structure and function. “Being able to identify patients with heart failure with preserved ejection fraction is not only key to improving patient outcomes through early diagnosis but also for us to understand the causal mechanisms underlying the disease so we can develop future targeted therapies”, says Professor Li-Ming Gan, Chief Scientist and Senior Medical Director, IMED Biotech Unit, AstraZeneca. Damage to the endothelium The results of the study, which is the first of its kind, show that 75 per cent of the patients had what is known as microvascular dysfunction. This is a disease in which the coronary artery shows no sign of narrowing or plaque in radiographs, but has damage to the endothelium that coats the inside of the blood vessels. The blood vessels do not work as they should, which can lead to adverse changes in the heart muscle. The researchers therefore draw the conclusion that microvascular dysfunction can be a critical underlying disease mechanism in patients with heart failure in which the ejection fraction is preserved. “The results will be useful in identifying patients at risk of developing the disease, but above all they’ll make an essential contribution to the development of drugs for patients with heart failure with preserved ejection fraction,” says Lars Lund, Senior Consultant and Professor at Karolinska Institutet’s Department of Medicine in Solna. The results will be presented at the European Society of Cardiology (ESC) congress in Munich and are published in The European Heart Journal. The project was financed by AstraZeneca and the researchers are in receipt of grants from the Swedish Research Council, the Swedish Heart and Lung Foundation, the U.S. National Institutes of Health, the American Heart Association, the National Medical Research Council of Singapore, and the Academy of Finland, Finnish Foundation for Cardiovascular Research. Publication “Prevalence Of Microvascular Dysfunction in Heart Failure with Preserved Ejection Fraction: PROMIS-HFpEF” Sanjiv J. Shah, Carolyn S. P. Lam, Sara Svedlund, Antti Saraste, Camilla Hage, Ru-San Tan, Lauren Beussink-Nelson, Maria Lagerström Fermer, Malin A. Broberg, Li-Ming Gan and Lars H. Lund. European Heart Journal, online 27 August 2018, doi: XX

On 23 August, Karolinska Institutet handed the remains of seven indigenous Australians over to the Australian Government. The remains were part of Karolinska Institutet's anatomical collections from the mid- to late-1800s. They were transported to Sweden by a sea captain, a doctor and an exploratory zoologist, but have now been returned to Australia. The ceremony took place in Stockholm and was attended by representatives of Karolinska Institutet, the Australian Ambassador to Sweden, and Saami representatives. “It is very important for these communities that the remains of their ancestors will now rest in their homeland, in dignity and peace,” said Jonathan Kenna, Australia's Ambassador to Sweden, after the ceremony. The Australian Government's repatriation program supports the unconditional repatriation of the remains of indigenous peoples – Aboriginal and Torres Strait Islanders – from foreign collections and private owners, which contributes to reconciliation. “I would like to thank everyone from Karolinska Institutet and the Swedish State who worked long and hard so that this would come to pass,” said Jonathan Kenna. The President of Karolinska Institutet, Ole Petter Ottersen: “On behalf of KI, I am very pleased to be able to help restore the humanity and dignity of these seven individuals – it is our moral obligation to do so. There is nothing we can do to alter the mistakes of yesterday. What we can do is make sure that we get it right today,” he said. The President of the Sami Parliament Plenary Assembly, Paul Kuoljok, participated in the ceremony, in which a joik was sung directly to the seven individuals. The ceremony ended with a healing circle ritual, conducted by Johannes Vestly.