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Two colleagues at Swetox, a national research centre in chemicals, health and environment, have been awarded € 6,000 for having developed a new more humane method of performing blood tests on rats and mice. The prize is presented by EPAA (the European Partnership for Alternative Approaches to Animal Testing), which is a collaboration between the European Commission and the largest companies in the pharmaceuticals and chemicals sectors. Mattias Öberg, a lecturer at the Institute of Environmental Medicine and Swetox, works together with his prize-winning colleague at the Unit of Toxicological Sciences at Karolinska Institutet, which constitutes a key part of Swetox. He describes in his blog how during the course of their work at the Unit they have developed a new approach that means blood tests can be performed on laboratory animals without the animals needing to be strapped down, something which until now has been common practice. The prize-giving ceremony took place in Brussels on 22 November. Swetox – the Swedish Toxicology Sciences Research Center – is a collaboration between eleven Swedish universities in toxicological research and training.

How can we identify a system that recruits voluntary life-savers in the local environment? This question was the firing shot for a research project at Karolinska Institutet which resulted in the SMS Livräddare (Life Saver) app. Today the app has 38,000 experts in cardiopulmonary resuscitation linked to it, and ready to save lives. The research project is now being rewarded with the Athena Award, Sweden’s biggest prize in clinical research. Leif Svensson, Professor at KI and working at the Centre for Resuscitation Science where Jacob Hollenberg is head and principal manager, was the person who took the initiative for the research project SMS Livräddning. The project, which is now being rewarded with the Athena Award, has been headed by Mattias Ringh, specialist doctor at the cardiac clinic at Södersjukhuset and a researcher at the Centre for Resuscitation Science. The idea behind the app is that those who have registered on it and find themselves within a radius of 500 metres from someone who is suffering from cardiac arrest receives a text message on their mobile from the alarm centre at the same time that the ambulance service is informed. Those who receive a text message can quickly get to the person affected and start cardiopulmonary resuscitation before the ambulance arrives.

Peter Ueda, postdoc at the Department of Medicine, Solna, Karolinska Institutet, has won the Researchers’ Grand Prix 2017 and is therefore the Swedish champion in making a four-minute presentation of his own research. During his presentation, Peter Ueda explained how he uses large data files containing millions of observations to discover how treatments for a wide range of illnesses can be improved. Peter Ueda also carries out research into the side-effects of pharmaceuticals and how well they actually work, as well as finding new ways to identify patients with a high or low risk of illness (for example myocardial infarction) or adverse reactions, so that treatment can be tailored to the individual. Congratulations on winning the Researchers’ Grand Prix! How does it feel? “It feels good,” says Peter Ueda. Why did you take part in the competition? “I was contacted by the press office at KI, who wanted me to be involved, so I accepted. I usually say yes to things. Unless I say no.” What was the most difficult part? “Being nuanced and restrained, while at the same time not holding back so much that you lose your flow.” What was the most fun? “Drawing pictures. I love drawing. The medical profession is cool, but it’s very much algorithm-based and there aren’t many opportunities to express yourself. And you never get the chance to be ironic, which I had now. And it was fun to work with the skilled and enthusiastic organisers.”   What do you think the prize will lead to? “I’m not a big fan of the trend for us researchers to sell our ideas and visions like a group of inspirational speakers. The Americanised form of presentation isn’t quite compatible with the scientific approach, where you have to be critical and constantly reassess assumptions and hypotheses. I tried to strike a tone in which I avoided being boring while still not being another Steve Jobs. I hope to be able to continue to develop this.” What are your top tips to other researchers who want to be better at presenting their research? “Question the format. Is a lecture really the best thing to do, given what you want to achieve? For example, there’s a lot of evidence to show that listening to lectures isn’t very effective if it’s about teaching, so maybe you should use some other form of communication. “Script first, then the pictures. In this age of PowerPoint, the usual approach is to start by creating slides and then having the presentation consist of you talking about the slides. Start instead with a script and then make pictures to support your narrative. A picture plus a narrator’s voice are the same components as in a documentary film, and no editor makes the film first and then thinks about what to say about the pictures! “Slides are free. You’re often given an instruction to make a presentation of ‘no more than X slides’. This isn’t logical, as the limiting resource is time and not images, after all they’re free. Divide up the content into as many pictures as are required to help people understand what you’re talking about.” During the Researchers’ Grand Prix, researchers compete to present their work in the most entertaining and informative manner possible in only four minutes. The winner is decided by the audience together with a panel of expert judges.

New research from Karolinska Institutet reveals that high levels of polyunsaturated fatty acids in children’s blood are associated with a reduced risk of asthma or rhinitis at the age of 16 years. The study is published in The Journal of Allergy and Clinical Immunology. Allergic diseases such as asthma and rhinitis are common and often debut in childhood. Today we know that disease risk is affected by both hereditary and environmental factors. To date, the present study is the largest to investigate the association between levels of long-chain omega-3 and omega-6 fatty acids in the blood and subsequent development of asthma and other allergic diseases. This study was conducted as part of the Swedish birth cohort BAMSE, and is based on analyses of omega-3 and -6 fatty acids in blood samples from 940 children. Less likely to develop asthma or rhinitis The results show that children who had higher blood levels of long-chain omega-3 fatty acids at the age of 8 years were less likely to have developed asthma or rhinitis by the age of 16 years. High levels of an omega-6 fatty acid called arachidonic acid were associated with a reduced risk of asthma and rhinitis at 16. Among children with asthma or rhinitis at the age of 8 years, higher blood levels of arachidonic acid were associated with a higher probability of being symptom-free at age 16 years. “Since allergies often debut during childhood it is of particular interest to study if children’s environment and lifestyle affect the development of these diseases,” says study leader Anna Bergström, researcher at the Institute of Environmental Medicine, Karolinska Institutet. Some fatty acids must be sourced from foods Polyunsaturated fatty acids are essential to life, and the omega-3 and omega-6 fatty acids that the body is unable to produce itself must be sourced from foods such as nuts and certain vegetable oils; and long-chain omega-3 fatty acids are primarily found in oily fish. “These new results and those of a previous study we carried out support the current dietary guidelines to eat fish two to three times a week and to vary between oily and lean fish,” says Dr Anna Bergström. The study was financed by the Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning (Formas), the Swedish Research Council, the Swedish Research Council for Health, Working Life and Welfare (Forte), the Swedish Asthma and Allergy Association, the Swedish Heart and Lung Foundation, Stockholm County Council and the European Commission. Publication “Polyunsaturated fatty acids in plasma at 8 years and subsequent allergic disease” Magnusson J, Ekström S, Kull I, Håkansson N, Nilsson S, Wickman M, Melén E, Risérus U, Bergström A. Journal of Allergy and Clinical Immunology, online 5 December 2017, doi: 10.1016/j.jaci.2017.09.023

A new study in EBioMedicine by researchers at Karolinska Institutet and the Medical University of Vienna, Austria suggests that immune response in early childhood to a handful of allergen molecules can predict the onset of allergic rhinitis and asthma in adolescence. These findings could accelerate the development of preventive strategies and novel treatments for respiratory allergy in children. Allergic diseases belong to the most common causes of chronic illness and create a high burden of suffering due to the great impairment in quality of life. Immunoglobulin E (IgE) sensitisation to allergens has been shown to be associated with increased risk of allergic diseases and asthma. In a new study, researchers at Karolinska Institutet and the Medical University of Vienna have used a novel approach to identify which specific allergens can predict the transition from IgE sensitisation in early childhood to the development of respiratory allergy later in life. Studied more than 100 allergens Using a large panel of micro-arrayed allergens, the researchers analysed IgE reactivity to more than 100 allergen molecules from more than 40 allergen sources. The study included data from 786 children from the Swedish birth cohort BAMSE, and 248 children from the UK birth cohort MAAS. A molecular signature of IgE against a handful of allergens at ages 3–5 years predicted respiratory allergy with more than 90 per cent probability up to adolescence in the two geographically separate populations. In the Swedish population, the identified risk allergens came from peanut, birch, grass and cat, and in the British population from dust mite, grass and cat. “Our results show that only a few regional allergen molecules are likely to be of importance for predicting the onset and persistency of respiratory allergic diseases and should be the focus for preventive strategies and targets for novel therapies”, says Professor Magnus Wickman at the Institute of Environmental Medicine, Karolinska Institutet. According to the researchers, the findings suggest generalisability of the data across populations and a possibility of developing individualised risk prediction charts for allergic respiratory diseases. These tests could potentially be used by paediatricians or physicians who see children at a young age. The BAMSE project is an ongoing longitudinal, population-based prospective birth cohort including more than 4,000 children born between 1994 and 1996 in Stockholm, Sweden. Researchers at Karolinska Institutet are currently conducting the eighth follow-up of the project as the participants have reached an age of 22–24 years. Might be able to prevent chronic disease “Respiratory diseases that start in childhood or adolescence often last for life, and birth cohorts are essential for understanding the life course of allergy. We might be able to prevent childhood allergy and asthma from becoming chronic severe diseases in adulthood if the children are identified and receive effective treatment at an early stage”, says Professor Magnus Wickman. The study was made in collaboration with European researchers within the EU-funded programme MeDALL (Mechanisms of the Development of Allergy). It was supported by research grants from the Swedish Asthma and Allergy Foundation, the Stockholm County Council (ALF), the Swedish Research Council, the Swedish Heart-Lung Foundation, the Swedish Cancer and Allergy Foundation, the King Gustaf V 80th Birthday Foundation, the Hesselman Foundation, The Konsul Th C Bergh Foundation, the Magnus Bergvall Foundation, Swedish research council for health, working life and welfare, the Austrian Science Fund (FWF) and by the European Commission’s Seventh Framework Programme MeDALL. Publication “Detection of IgE reactivity to a handful of allergen molecules in early childhood predicts respiratory allergy in adolescence” Magnus Wickman, Christian Lupinek, Niklas Andersson, Danielle Belgrave, Anna Asarnoj, Marta Benet, Mariona Pinart, Sandra Wieser, Judith Garcia-Aymerich, Alexandra Baar, Göran Pershagen, Angela Simpson, Inger Kull, Anna Bergström, Erik Melén, Carl Hamsten, Josep M. Antó, Jean Bousquet, Adnan Custovic, Rudolf Valenta, Marianne van Hage EBioMedicine, online 14 November 2017

On 10 December it is once again time for the Nobel Prize ceremony. One of the three researchers awarded the Nobel Prize in Chemistry is Jacques Dubochet, who pioneered a flash freezing method for biomolecules that avoids the forming of ice crystals in water. The cryo-electron microscopy technique provides us with detailed high-resolution images of molecular structures. The Nobel Prize-winning method was taken to Karolinska Institutet by Jacques Dubochet’s colleague and friend Lars Norlén, to be applied to biological tissue. What were your first thoughts when you heard about Jacques Dubochet’s Nobel Prize? – It felt fantastic, partly because he thoroughly deserves it. It is confirmation of the value of the methods and techniques. Jacques Dubochet and I worked together when I was doing my postdoc with him between 1999 and 2004. We have worked extremely closely and remain good friends. After my postdoc, I returned to Karolinska Institutet and built an identical lab here. Jacques Dubochet is now retired but I still discuss all of our articles with him. What is he like, as a researcher and a person? – Jacques Dubochet is a classic example of the original researcher, stubbornly running his own race with extreme stamina, way beyond the mainstream. He has always worked in small groups and has been able to follow his own path. I consider him to be a true original in a purely positive and genuine manner, incredibly dedicated, enthusiastic, warm and friendly. He is not a domineering personality and has never maintained a high profile. How is cryo-electron microscopy used at KI? – Our cryo-electron microscopy laboratory is located at the Department of Cell and Molecular Biology, CMB, where we have a team of three researchers studying the skin barrier. It was here at CMB that we implemented the technique as per Jacque’s model and later refined it. Flash freezing proteins in solution, allowing us to study individual molecules in test tubes, has had enormous success worldwide and the technique is also currently being used at SciLifeLab. However, Jacque’s own work in recent years was mostly aimed at developing the technique for applications with cells and tissues in their natural environment, rather than in test tubes. And this is what myself and my two colleagues are working on. How do you go about studying the skin? – We flash freeze tissue samples taken from the skin, normally a small piece of skin from the forearm. We then place the skin in liquid nitrogen, flash freezing it so quickly that the water in the tissue doesn’t have time to form ice crystals. In order to succeed, we need to achieve a temperature of -140°C within 20 milliseconds. This holds everything in its exact position and the water becomes solid while maintaining its liquid form, much like if one were to solidify all of the water in an aquarium with all of the fish remaining exactly where they were. Image resolution in cryo-electron microscopy is related to sample thickness. The skin’s horny layer contains very little water, meaning that we are generally able to flash freeze the skin without forming ice crystals. We use a refrigerated diamond knife to slice 20-30 nanometre skin samples. These thin frozen slices are then placed on a grid before being placed in a refrigerated cryo-electron microscope. We then fire electrons at the skin sample to obtain an image of the tissue. Under ideal circumstances we can achieve a resolution of a few angstrom, i.e. with molecular resolution. What conclusions have you come to about the skin barrier? – We have been working to determine the structure of skin at molecular level using Jacques Dubochet’s method for almost 20 years now. The skin barrier retains water in the body but also prevents chemicals, such as medicines, from penetrating. We succeeded in uncovering the basic structure in 2012. This year, by combining Jacques’ cryo-electron microscopy method with molecular dynamic simulation techniques, we succeeded in creating a ‘living’ atomic model of the skin barrier. This can be used to determine pharmaceutical penetration through the skin and now we hope to be able to calculate how a number of medicines can be more easily absorbed through the skin. To be able to administer medicines through the skin would be advantageous as it would bypass the liver and intestinal mucosa and avoid side effects. If the model can be used to screen medicines through simulation, we also hope to be able to radically reduce the use of laboratory animals. What does the attention focused on this technique mean to your research group? – Here at KI, we are well advanced when it comes to using cryo-electron microscopy on cells and tissues with skin as a reference. We hope that the scientific community opens its eyes to the opportunities offered by the method and understands that Sweden is an international leader in the field. The problem is that the microscope is extremely expensive. The entire procedure is costly, time-consuming and requires high levels of specialist expertise. However, if we want to understand the structure and function of cells at a molecular level, there is currently no alternative to Jacques’ technique. Sooner or later, we must take the step from test tubes to living cells and this is where tissue cryo-electron microscopy comes in. Text: Maja Lundbäck  

Comment: In a recently issued report, the Swedish National Audit Office notes that the state universities and other institutions of higher education have accumulated over twelve billion kronor (SEK) in unused appropriations and other surpluses. The Swedish National Audit Office believes that this indicates an inefficient utilisation of resources, and recommends that the Swedish Government improve its governance. Karolinska Institutet’s public capital amounts to approximately SEK 1.5 billion, and KI has already commenced efforts prior to this report to reduce it to a lower level. “For a long time now we have called for a definition of what level of public capital is appropriate for an organisation such as ours, as there are no rules presently, and I welcome this review by the Swedish National Audit Office,” comments Eva Tegelberg, Director of Finance of Karolinska Institutet. The approximately SEK 1.5 billion that the Karolinska Institutet has in public capital is distributed not only among its 22 departments and their research groups, but also among asset management and holding companies. In recent years, the amount has increased approximately at the same rate as the revenues. Thus, measured as a percentage of revenues, the public capital of the Karolinska Institute has not increased. The Swedish National Audit Office concluded in its report that most institutions of higher education have commenced with work to slow down this growth, and that the public capital has begun to decline at half of them. Efforts have also been initiated at Karolinska Institutet to reduce the public capital. “It is clear from the forecasts in our budget estimates that KI will reduce its public capital over the next few years,” remarks Eva Tegelberg.

In line with an increasing proportion of healthcare being conducted outside the emergency hospitals, there is now a major challenge arising – how to ensure training and clinical research maintain priority. The annual conference ‘InFuturum’, with Karolinska Institutet and Stockholm County Council as hosts, focused on management and leadership in the new healthcare landscape. When healthcare managers met representatives from the country’s medical faculties at Aula Medica on 23 November, it was to discuss the future challenges within the new healthcare landscape. This upcoming spring, it is expected that a new law on highly-specialised care will be pushed through. Hospitals will now focus on the patient groups they know best. Seriously ill patients are treated in hospitals providing highly-specialised care, while others are cared for in nearby emergency care hospitals or within primary care. The reshaping is called ‘level structuring’ and means that the patient receives the right are at the right level. Karolinska University Hospital focuses on highly-specialised care, and next year will see the opening of the new highly-specialised intensive emergency department for only the most seriously ill patients. This will have consequences to research and training at KI. “The future is already here. The conditions have changed and we therefore have new challenges in how research and training is to be organised. Healthcare will be given through a greater number of providers and research must be conducted where the patients are,” said Ole Petter Ottersen, Vice-Chancellor at  Karolinska Institutet, when he introduced the conference together with Malin Frenning, Director at the Stockholm County Council (SLL). Malin Frenning emphasised the strong link needed between healthcare and educational institutions, but also between the institutions themselves. “We need a forward-looking way to meet the healthcare challenges of the future. To achieve success we also need to deepen and improve the collaboration between the university and colleges,” she said. The new intensive emergency department affects medical training The fact that there aren’t expected to be many patients at the highly-specialised intensive emergency department at Karolinska University Hospital, together with there being only a limited number of diagnoses, will all impact the medical students. In order for the medical students to get the right training, it must be organised in a new way. The entirety of medical training is simultaneously facing a reshaping. The day before the conference the government issued a proposal for an one-year basic service requirement for medical students. Jens Schollin, Senior Professor at Örebro University, who created the proposal, was also present. “The basic service requirement should focus on primary care and emergency care, and there should also be a freedom of choice. We want people to know one or two specialities,” he said. The basic service requirement, which replaces AT, is introduced on condition that a proposal for an entirely new six-year medical training period will be put through. Stefan Lindgren, professor at Lund University, was tasked by the government to investigate the new medical training. “If the students are trained in professional roles, we need to have a focus on the environments where they can actually learn. Training has previously focused on the serious illness processes, but we need more focus on chronic illness processes,” he said. Academic specialist centres medical students new training areas Sofia Ernestam, operations manager at the Academic Specialist Centre [Akademiskt specialistcentrum] within SLL, with the Medical centre for Rheumatology, Centre for Diabetes and Centre for Neurology, considers the Academic Specialist Centre to be an excellent training location for students, but also a good example of a business where research-intensive care is already carried out. “But we can learn so much more, and in addition, we need to have academically-driven individuals who are committed, involved and who push development forward. By moving closer to primary care, we will be able to ‘capture’ these patients and do studies, perhaps before they become ill. But we need to network more in order to get good results and work together with primary care,” she said. The clinical research follows the patients Also of the opinion that the clinical research should follow the patients was Annika Tibell, associate hospital director at Karolinska University Hospital: “Clinical research must, as far as is reasonably possible, follow the patients. This means that the network of researchers reaches out further to other parts of the healthcare chain,” she said. Anna Martling, professor of surgery at Karolinska Institutet, shared some examples of how she networks with hospitals across Sweden - known as ‘clinical networking research’. In her research on colon and rectal cancer, she needs to screen 4,000 patients in order to achieve a sufficient amount of patient data. “Building clinical networks was necessary in order to have access to patients. We went and spoke with every hospital in each region and found 27 centres that are now involved with us. We also have to train doctors and nurses to go into new roles and begin researching. This needs resources and takes time, but we’re now underway with the study,” she said. Text: Maja Lundbäck

2,400 women have signed the academic community’s #metoo – #akademiuppropet, the University Call to Action, as having been subjected to sexual harassment or other forms of violations of personal integrity based on their gender. Stories also come from the staff and students at the Karolinska Institutet. The Call to Action is now seen as an opportunity to transform the academic community at its foundation. “Karolinska Institutet takes these testimonies presented in the Call to Action extremely seriously. KI must be an organisation where neither the staff nor its students are subjected to or subject another to violations of personal integrity of the kind that those in the academic community are now talking about,” says Karin Dahlman-Wright, Pro-Vice-Chancellor and responsible for gender mainstreaming issues and work environment at Karolinska Institutet, and continues: “KI must be prepared to investigate suspected cases and to provide the victim with adequate support and assistance. A part of this, is that leaders at all levels are alert, responsive and act forcefully when suspicions of sexual harassment arise.” KI actively works to combat discrimination, including via regular educational efforts and workshops for both employees and students. Equal treatment and equal opportunities is also an element of various leadership courses and courses related to academic supervision, as well as the courses and educational programs for students. Plus, in addition to support for students and staff, KI funds a student ombudsman and a graduate student ombudsman where undergraduate and graduate students can turn to. Surveys do not provide the whole picture In order to measure the extent of the problem of sexual harassment and other discrimination at KI, questionnaire surveys have been conducted regularly among staff and students. However Caroline Olsson, who has been the coordinator for equal opportunity and broadening recruitment at KI for many years, is of the view that these are blunt instruments, and that staff surveys and actual complaints filed do not provide an accurate picture of how substantial and complex the problem really is. “#akademiuppropet shows that violations of personal integrity in the academic world have been normalised. Some women haven’t even verbalised either to themselves or someone else that they have been subjected to such an incident. Only now do they begin to think about what happened and recall the events, which is now described as violations of personal integrity. On the other hand, in some cases it is very clear to both those who have been the victim and to those who have been the perpetrator – and many in the immediate environment know very well what is going on,” says Caroline Olsson. Sexual harassment has many nuances Elisa Floriddia, Chair of the KI Postdoctoral Association at KI thinks #akademiuppropet strikingly illustrates both the extent and the many nuances of sexual harassment that exists. “I would really hope that the most extreme cases of sexual harassment get reported; but I’m really not so sure. Many are too afraid to put their job at risk, especially as many postdocs only have temporary contracts. In addition, it is sometimes difficult to promptly recognize signs of harassment, as we all grew up in in a gender biased/discriminatory society,” she says. The Junior Faculty’s Chair Emma Andersson thinks that #akademiuppropet reveals the inequalities, how unequal the power relationships between men and women are in the professional world, something that is a particularly hard burden for young female academics. “I truly hope that now more attention will be devoted to microaggression, inappropriate behaviour and unconscious prejudices at all levels of academia. At the same time, I hope that the campaign does not eat away at the trust and the great progress we are making in terms of good cooperation and mentoring between men and women or non-binary* individuals,” she says. Many simply do not know where to turn to In a survey that Junior Faculty made of its members in 2017, nine percent (approximately 400 of those responding) stated that they had been a victim of discrimination in one way or another. Of these, 72 percent had not sought assistance or support at all; and 80 percent of those who sought help had not received adequate support. 52 percent did not know to whom, or where, they could turn to if they were subjected to such an incident. Therefore, despite KI’s systematic efforts to combat discrimination, the problem is difficult to solve as it is rooted in power imbalances, situations of dependency and structural problems in the competitiveness of the academic world. “The problem persists in the entire academic research community, not only at KI. This often involves a power relationship, and many choose not to take the matter further, perhaps for fear that they will suffer negative consequences,” Caroline Olsson says. So how can we address the problem? Caroline Olsson describes a kind of “culture of silence” that exists within academic institutions throughout the world, a normalisation of discrimination. It may be that many in a group keep quiet, even though they know that someone is being subjected to abuse. “#akademiuppropet is a way to break this silence. This is a unique opportunity for the academic community in general and KI in particular to change the culture that has for so long maintained power imbalances between the genders. The evidence testifies to that this is a structural problem, not simply individual individuals who ‘were treated poorly’ or ‘got into trouble’,” she comments. Elisa Floriddia thinks it’s primarily about education, that everyone at KI should know how to best deal with sexual harassment and whom to contact for assistance and information, anonymously. Secondly, it is about continuing the efforts to implement a culture of mutual respect and gender equality. “Sexual harassment stems from discrimination and, in turn, from prejudice. The KI Postdoc Association thinks that in addition to explicit prejudices, we should become be even more aware of our unconscious prejudices, and find tools to neutralise them,” she says. Emma Andersson has hopes that KI will implement a course on unconscious prejudices for everyone who reviews and makes decisions regarding the approving of applications for funding or the hiring for employment. “The Junior Faculty also thinks that increased transparency and policies concerning prejudices should be incorporated into in all decision-making and evaluation processes, as subjectivity has proven to be a common cause for discrimination. Increased gender equality and diversity among members of the boards, departments, workgroups and dissertation defence committees is also needed. This will ultimately lead to a meritocracy* where the best academic researchers, irrespective of gender, get promoted,” she remarks. KI must raise the level of ambition Both Elisa Floriddia and Emma Andersson emphasize that KI must have an organisation which takes a very strong stand against discrimination and sexual harassment. Department heads and the senior management need to show that this is wrong. It must also be clear, where one can and should turn to. “It is important that complaints of sexual harassment are handled properly and taken seriously. Perpetrators must suffer the consequences of their actions,” stresses Elisa Floriddia. Since the 1 January 2017 when the provisions of the Swedish Anti-Discrimination Act were made more stringent, KI has imposed upon itself the requirement to analyse the risks that are present for discrimination and sexual harassment to arise in the institution. “After that, we must then analyse what the risks are due to and then work on both prevention and promotion. KI must raise its level of ambition in this work and with this, the leadership in the academic community has a vital role. Ultimately, it is us at the management level who have the responsibility for combating the kind of abuses and violations of personal integrity that women testify to in #akademiuppropet,” stresses Karin Dahlman-Wright. * Meritocracy is a social order in which individuals are ranked in a hierarchy and the distribution of social rewards is according to ability and merits, usually measured by educational attainment and qualifications. Source: NE * “Non-binary” is what the person who identifies as between or beyond the female-male division of gender might call themselves. Source: RFSL Text: Helena Mayer Facts The legislation is clear: sexual harassment is illegal and suspected cases must be investigated. Anyone who has been found guilty risks, as an employee, being dismissed from their job, or suffering a reduction in salary; or as a student, being expelled from the educational programme.

Emma Frans, researcher at the Department of Medical Epidemiology and Biostatistics, was awarded the Swedish Grand Prize for Journalism in the Voice of the Year category on 23 November “for addressing the resistance to facts in such an entertaining manner and with scientific precision revealing the Internet's incessant myths”. 1. What does it feel like to have won the Swedish Grand Prize for Journalism in the Voice of the Year category? – I feel extremely happy and proud. And also a little bit surprised at winning the Swedish Grand Prize for Journalism because I don’t consider myself to be a journalist but a researcher. 2. Why do you think the prize went to just you? – I think I contribute to a unique perspective in the public dialogue that feels important and relevant in today’s society and times where it is becoming increasingly important to think scientifically. 3. What do you think the prize will lead to? – I hope this will send signals to academia that the third task needs to be prioritised and that researchers need to be more visible to the public. 4. How would you like to continue to work on/against resistance to facts? – I will continue to advocate a scientific attitude and emphasise the importance of science and facts in the public debate. But I also fight to win the public’s trust. We listen to those we have faith in and that is why we can counteract resistance to facts by ensuring that those who advocate facts have the people’s trust. 5. What is your best advice on how to separate fact from fiction in the torrent of information we live in today? – It’s important that statements have sources that can be traced and that are credible. Senders who are independent are more credible than people who are driven by financial or political interests. Then it’s important to check underpinning information as a whole and not just select the information that backs up what we already think or what we want to believe. 6. What can motivate researchers to prioritise popular scientific communications to the public? – The fact that I was awarded the Swedish Grand Prize for Journalism is extremely motivating for me personally, but I think it also sends signals to other researchers about how very much appreciated it is to have people who fight to reach out with knowledge. Emma Frans Emma Frans is a post-doc researcher at KI, researching in psychiatry and pharmaceutical epidemiology. She recently published the book Larmrapporten – att skilja vetenskap från trams [Scare Stories – Separating Science from Nonsense] (Volante).  

iGEM Stockholm 2017 has maintained the legacy of iGEM Stockholm by winning a gold medal for the third consecutive year. The 2017 team was additionally nominated as one of the best entrepreneurial projects. After ten months of intense work, iGEM Stockholm showcased their project at the Giant Jamboree which is the grand and final event of the The International Genetically Engineered Machines (iGem) competition in Boston, hosting over 300 teams of students from over 42 countries across the world. The teams compete with their innovative project ideas which all aim to solve real-world problems by using synthetic biology. This year, the team of iGEM Stockholm 2017 attracted many iGEMers, judges and company representatives, not only with their innovative and futuristic project, but also with their compelling presentation and well-designed poster. Additionally, iGEM Headquarters praised Stockholm’s high diversity and gender balance as that of an “exemplary iGEM team”. With leaps and bounds in a yearlong journey, the team succeeded not only with great research results, but also with a strong public outreach called “Democratic Biology” and a well executed fundraising strategy.

For 2017, KI researchers Anca Catrina and Olov Andersson have been awarded the Consolidator Grants from the European Research Council (ERC), and will receive funding of 2 million euros in total for a project duration of five years. After evaluating 2,538 research proposals, the ERC announced on 28 November the awarding of Consolidator Grants that go to 329 top researchers across Europe. The funding, a part of the EU's Horizon 2020 research and innovation programme, is worth in total 630 million euro. Anca Catrina Project: Towards prevention of autoimmune diseases: the case of rheumatoid arthritis (PREVENT RA) The project aims to elucidate the early mechanisms by which systemic autoimmunity, which is triggered by environmental challenges at mucosal sites of genetic susceptible individuals, target the joints to induce chronic inflammation. This will allow efficient identification of RA-susceptible individuals and development of new tools for risk estimation in each of these individuals, as well as novel ways of intervention in order to delay, or in the best case prevent disease development. By shifting the time (to phases before joint inflammation occurs) and the ways of interventions (to drugs targeting early and previously unknown pathogenic mechanisms), expected results from the current project are beyond the current state of the art in RA. Anca Catrina profile page Anca Catrina research group Olov Andersson Project: In vivo drug discovery for cellular reprogramming to β-cells – towards a future regenerative therapy for diabetes Both type 1 and later stages of type 2 diabetes feature a reduction of functional β-cells, a key pathologic event that causes or exacerbates the dysregulation of glucose levels. The project will focus on identifying extracellular factors that can induce cellular reprogramming to β-cells and thereby increase the β-cell mass. First the researchers will screen for factors that can induce cellular reprogramming to β-cells in zebrafish, since it is important to investigate the signaling system in a living organism. Next is a follow up on the hits to assess their translational potential and gain further mechanistic insight into the reprogramming process and hopefully develop better drugs treating diabetes. Olov Andersson profile page Olov Andersson research group ERC Consolidator Grants  The ERC Consolidator Grants are awarded to outstanding researchers of any nationality and age, with at least seven and up to twelve years of experience after PhD, and a scientific track record showing great promise. Research must be conducted in a public or private research organisation located in one of the EU Member States or Assoiated Countries. The funding (maximum of €2 million per grant), is provided for up to five years and mostly covers the employment of researchers and other staff to consolidate the grantees' teams.

Postmenopausal hormone therapy is not associated with increased risk of stroke, provided that it is started early, according to a report from Karolinska Institutet published in the journal PLOS Medicine. Roughly three in ten women in the menopause transition are afflicted by symptoms that seriously affect their wellbeing, such as hot flushes, dry mucosa and insomnia. However, although the symptoms can be treated effectively with female sex hormones, prescriptions have been low over the past 15 years as researchers have demonstrated a link between such therapy and an increased risk of certain diseases, including stroke. There is still, however, a need for more research on the issue, as the risk can be influenced by the time of the treatment and other factors, reasons Karin Leander, researcher at Karolinska Institutet’s Institute of Environmental Medicine. “New research shows us that hormone therapy actually has a positive effect on blood vessels if initiated early on in the menopause, but not if initiated late,” says Dr Leander. “So there was reason to re-examine whether hormone therapy is linked to the risk of stroke, taking, of course, the time of administering into consideration.” Data from several cohort studies Dr Leander and her colleagues have now analysed data on postmenopausal hormone therapy from five Swedish cohort studies covering a total of 88,914 women, combined with data from national registries on diagnoses and causes of death during a follow-up period. Hormone therapy was not linked to increased risk of stroke (ischemic and haemorrhagic stroke combined) if the therapy was initiated within five years of menopausal onset, regardless of means of administration (oral, via the skin or vaginal), type of therapy (combination or oestrogen only), active substance and treatment duration. In sub-analyses, however, there was an observable increase in risk for haemorrhagic stroke (the less common form) if the therapy contained the active substance conjugated equine oestrogens. Drugs containing oestradiol, on the other hand, were not associated with a higher risk. A higher risk was also seen for both ischemic and haemorrhagic stroke if the treatment was initiated later than five years after the onset of menopause and contained conjugated equine oestrogens. Stroke risk may be eradicable “The risk of stroke seems virtually eradicable if treatment commences early, but it’s naturally important to take account of the increase in risk that exists under certain circumstances,” says Dr Leander. “These results provide doctors with a better scientific base on which to take decisions on treatment for menopausal symptoms.” The study was financed by Karolinska Institutet, the Swedish Stroke Association, the Swedish Research Council, the Swedish Heart-Lung Foundation and Norrbotten and Västerbotten county councils. Publication: ”Postmenopausal hormone therapy and risk of stroke: A pooled analysis of data from population-based cohort studies” Germán D. Carrasquilla, Paolo Frumento, Anita Berglund,Christer Borgfeldt,Matteo Bottai, Chiara Chiavenna, Mats Eliasson,Gunnar Engström,Göran Hallmans,Jan-Håkan Jansson,Patrik K. Magnusson,Peter M. Nilsson,Nancy L. Pedersen, Alicja Wolk, Karin Leander. Plos Medicine, online 17 November 2017

Serious liver and heart problems can affect children with Alagille Syndrome early in life. While there is as yet no cure, researchers at Karolinska Institutet have discovered that the liver disease part of the syndrome is caused by specific malformations of the bile ducts. The results, which are published in the journal Gastroenterology, were discovered with the aid of a new mouse model that can now be used to develop and test new therapies. Every year, a handful of children are born in Sweden with the rare genetic disease known as Alagille Syndrome. Some of them become very ill with chronic liver and heart problems, sometimes so serious that they require a transplant. The liver problems can also give rise to severe itching. Other possible symptoms of the disease, which is usually caused by different mutations of the JAGGED1 gene, are deformities of the eyes or bones, and sometimes growth disorders. The children can also develop problems with other organs, such as the kidneys. Little is currently understood about how the disease can develop and each symptom is treated separately. Point mutation interferes with signaling system Using mice with a mutation in JAGGED1 and similar liver and heart problems, the researchers have discovered that the mutation not only affects the development of certain cell types, but also controls the actual formation of the liver’s bile ducts. By substituting a specific amino acid in a so-called “Notch ligand” encoded by JAGGED1, they found that this single point mutation can interfere with the important Notch signaling system and disrupt communication between the Notch ligand and the Notch receptors. The interaction with the Notch 1 receptor failed, while communication with the Notch 2 receptor was possible. “The discovery is important and opens up possibilities for new, more specific treatments,” says Emma Andersson, assistant professor at Karolinska Institutet’s Department of Biosciences and Nutrition. “We hope to be able to use our mouse model to understand the disease better, predict which children will need a transplant and ultimately find a cure.” Liver samples from patients The researchers also obtained liver biopsies from patients, which they studied using RNA sequencing. “The liver samples were the most important piece of the puzzle for our study,” says Dr Andersson. “Thanks to them, we were able to verify that the results from our mouse model and cell experiments were actually relevant to humans and patients. I’m extremely grateful for these donations. By comparing RNA sequencing with the Human Protein Atlas, we’ve also been able to identify new markers for the bile ducts that confirm the malformations that develop in patients with Alagille Syndrome.” The study was financed from several sources, including the Daniel Alagille Award (EASL), the Swedish Research Council, the European Research Council, the Swedish Cancer Society, the Swedish Brain Fund, the Knut and Alice Wallenberg Foundation and the ICMC. Publication “Mouse Model of Alagille Syndrome and Mechanisms of Jagged1 Missense Mutations” Emma Rachel Andersson. Indira V Chivukula, Simona Hankeova, Marika Sjöqvist, Yat Long Tsoi, Daniel Ramsköld, Jan Masek, Aiman Elmansuri, Anita Hoogendoorn, Elenae Vazquez, Helena Storvall, Julie Netušilová, Meritxell Huch, Björn Fischler, Ewa Ellis, Adriana Contreras, Antal Nemeth, Kenneth C. Chien, Hans Clevers, Rickard Sandberg, Vitezslav Bryja, Urban Lendahl Gastroenterology, online 20 November 2017, doi: 10.1053/j.gastro.2017.11.002

A new method that evaluates how effective different combinations of antibiotics are against resistant bacteria is to be tested at several universities in Europe, including Karolinska Institutet. Christian Giske, a researcher at the Department of Laboratory Medicine, is Academic Lead for the EU-funded study, which will last for at least two years. Antibiotic resistance is a major global problem. In Europe, more and more patients develop sepsis caused by intestinal bacteria and which is very difficult to treat. “In Sweden, too, we come across bacteria that are very difficult to treat. We try to overcome this by using combination treatment; in other words, we give more than one antibiotic at the same time. The problem is that two preparations can sometimes affect each other negatively and cause side effects,” says Christian Giske. Now he is to collaborate with researchers at universities in a number of EU countries to test a new and rapid analysis method for demonstrating which antibiotic combinations are effective. Kill a given bacteria “It is important to know whether two preparations actually work or not. At the moment, when faced with an infection we have to guess how the preparations could work together. There are methods that evaluate whether several preparations together can kill a given bacteria, but these methods are time-consuming and you have to have access to research animals. The new method involves measuring the energy production in the bacteria to determine whether they are alive or dead. We expect that this new method will enable us to more quickly and more accurately predict whether the preparations will work,” he comments. The analysis method and associated test equipment to be tested have been produced by company Symcel which, together with the researchers, has received a total of EUR 3.6 million from Horizon 2020, an EU-financed research and innovation program. As well as Karolinska Institutet, universities in Denmark, Italy and Spain will also be taking part. “Together we have access to a variety of bacteria collections. We need a broad collection if we are to determine how robust the analysis method is. The laboratory in Denmark will focus on animal studies in mice which will act as a reference,” Dr Giske says. Patients with severe infections  The researchers will test not only how different types of antibiotics act two and two, but also in combinations of three antibiotics. They will also test antibiotics singly. Just four to eight hours’ analysis will answer whether the tested antibiotic combination is effective or not. “We will choose preparations that we normally use to treat patients. We will simulate what happens in patients with severe infections such as sepsis, even though the model is not specific for sepsis,” he comments. If the method turns out to be effective, it will benefit the thousands of patients in Europe who are affected by resistant bacteria every year. The hope is that the analysis method, if it is effective and robust, can be applied in practice at the major hospitals in Europe and other parts of the world. Text: Maja Lundbäck (in translation from Swedish)

In a study published in Diabetologia, researchers at Karolinska Institutet and the University of Tampere, Finland, report that an enterovirus vaccine can protect against virus-induced diabetes in a mouse model for type 1 diabetes. A vaccine for human use is now under development by the Finnish company Vactech Ltd. and its American collaborator Provention Bio. Type 1 diabetes is the most common, chronic, life-threatening disease in children, and continues to increase worldwide. Finland and Sweden have the highest incidence of type 1 diabetes in the world with more than 1 in 200 sufferers in Sweden. To date, the exact causes of the disease are not known. One of the environmental factors that has been touted as a potential cause is infection with common cold viruses known as enteroviruses. However, no firm evidence exists proving their role. No severe side effects In this study, the researchers have used an experimental mouse model to determine the involvement of these viruses through testing of the efficacy of a novel prototype vaccine in preventing type 1 diabetes after enterovirus infection. The vaccine prevented virus-induced type 1 diabetes and protected against other signs of virus infection without any severe adverse effects. “These results indicate the potential that such a vaccine has for elucidating the role of enteroviruses in human type 1 diabetes. If they prove to be involved, vaccination with an enterovirus vaccine would provide a viable preventative treatment for virus-induced type 1 diabetes”, says Professor Malin Flodström-Tullberg at Karolinska Institutet’s Department of Medicine, Huddinge, whose research group was responsible for the preclinical studies. Important step before studies in humans The study was done in collaboration with researchers at the University of Tampere who produced the prototype vaccine. Work is currently ongoing at the University of Tampere to develop a vaccine that targets a greater number of viruses, all of which have been implicated in causing type 1 diabetes. The model that was established together with researchers at Karolinska Institutet will be used as a platform to test further enterovirus vaccines in so-called proof-of-concept studies. These studies are necessary before progress to a clinical set-up in humans. Novel enterovirus vaccines for clinical use in humans is currently under development by Vactech Ltd., Finland, and its collaborator Provention Bio, USA. The research was supported by Tekes (Finnish Funding Agency for Innovation) and by Barndiabetesfonden (the Swedish Child Diabetes Foundation). The Tekes-funded consortium Therdiab includes, besides University of Tampere and Karolinska Institutet, several Finnish Biotech companies including Vactech Ltd. This news article is based on a press release from the University of Tampere. Publication “A Coxsackievirus B vaccine protects against virus-induced diabetes in an experimental mouse model of type 1 diabetes” Virginia M. Stone, Minna M. Hankaniemi, Emma Svedin, Amirbabak Sioofy-Khojine, Sami Oikarinen, Heikki Hyöty, Olli H. Laitinen, Vesa P. Hytönen, Malin Flodström-Tullberg Diabetologia (the journal of the European Association for the Study of Diabetes [EASD]), online 18 November 2017

In a large multidisciplinary project, researchers at Karolinska Institutet have explored different properties of an enzyme family called NUDIX hydrolases. The study, published in Nature Communications, reveals novel insights into their biological functions in human cells. The NUDIX enzymes are involved in several important cellular processes such as cellular metabolism, homeostasis and mRNA processing. Although highly conserved throughout all organisms, their individual structural, biochemical and biological properties remain largely unclear. To address this, Professor Thomas Helleday and Assistant professor Jordi Carreras-Puigvert at Karolinska Institutet’s Department of Medical Biochemistry and Biophysics and Science for Life Laboratory (SciLifeLab) initiated a collaborative study with researchers at Uppsala University, Stockholm University, the University of Ljubljana in Slovenia, and members of the Human Protein Atlas. Comprehensive enzyme profile map The collaboration has resulted in comprehensive data on individual properties and interrelationships of 18 human NUDIX enzymes, revealing four major structural classes. Using a novel algorithm, the researchers integrated all data creating a comprehensive NUDIX enzyme profile map. “This map reveals novel insights into substrate selectivity and biological functions of NUDIX hydrolases and poses a platform for expanding their use as biomarkers and potential novel cancer drug targets”, says Jordi Carreras-Puigvert. The multidisciplinary project included analyses in biochemistry, structural biology, functional genomics, gene expression, protein expression and bioinformatics. It was supported by the European Union–Marie Curie-FP7-People programme, the Torsten and Ragnar Söderberg Foundations and the Knut and Alice Wallenberg Foundation, among others. Publication “A comprehensive structural, biochemical and biological profiling of the human NUDIX hydrolase family” Jordi Carreras-Puigvert, Marinka Zitnik, Ann-Sofie Jemth, Megan Carter, Judith E. Unterlass, Björn Hallström, Olga Loseva, Zhir Karem, José Manuel Calderón-Montaño, Cecilia Lindskog, Per-Henrik Edqvist, Damian J. Matuszewski, Hammou Ait Blal, Ronnie P.A. Berntsson, Maria Häggblad, Ulf Martens, Matthew Studham, Bo Lundgren, Carolina Wählby, Erik L.L. Sonnhammer, Emma Lundberg, Pål Stenmark, Blaz Zupan & Thomas Helleday Nature Communications, online 16 November 2017

The doctoral supervision training programme introduced at Karolinska Institutet (KI) in 2008 has proved successful. A comparison of exit polls conducted since 2008 shows that doctoral candidates are increasingly satisfied with their education. Now, directors of doctoral studies are to provided with their next quality-assurance tool: At the turn of the year, Green Light will be introduced. “Our work is ongoing and we leave no stone unturned. Exit polls have been of great help,” says Marianne Schultzberg, Dean of Doctoral Education at KI. In June, a longitudinal study was presented comparing exit polls conducted on doctoral students between 2013-2016 with those from 2008-2012. The study clearly shows increased satisfaction among doctoral students. Of those responding between 2013-2016, 93 per cent agreed entirely or in part that overall they had received a good education. This compares with 89 per cent between 2008-2012. Dissatisfaction decreased from 12.8 per cent in the earlier period to 8.6 per cent. The response frequency to exit polls has increased to 83 per cent (from 75 per cent). “It is most gratifying to find that our work is paying off. Both with regard to how doctoral candidates assess their supervisors and the support they receive from study directors, supervisors and others, as well as the quality of doctoral education courses,” says Marianne Schultzberg. At the turn of the year, a new structural initiative will be introduced to ensure the quality of doctoral education throughout KI; Green Light. This means that, prior to recruiting new doctoral candidates, every department must assess whether the preconditions exist for a high quality doctoral education – including sufficient time and expertise for supervision, as well as adequate financing. “Even if in the vast majority of cases these preconditions exist, we believe that the simple fact of raising the issue will have an effect. Departments have had the autumn to prepare their Green Light procedure,” says Marianne Schultzberg. Obligatory supervisor course It is currently obligatory for those researchers wishing to recruit and supervise doctoral students to take either KI’s Introductory Doctoral Supervision Course, introduced in 2008, or an equivalent course. “This has proved to be an excellent initiative. KI’s supervisor course is in great demand and always fully subscribed,” Marianne Schultzberg says. According to Marianne Schultzberg, KI’s researchers demonstrate enormous enthusiasm and commitment when it comes to doctoral supervision. “This represents four years of collaboration. It is a rewarding process to see someone develop,” she says. Doctoral students also confirm that expertise and dedication among supervisors have increased since the introduction of the course. According to the exit-poll study, 80 per cent would recommend their own supervisor to prospective doctoral candidates – an increase from 74 per cent between 2008-2012. The supervision problems demonstrated by the exit polls – the lack of discussion at theoretical level and about the candidate’s postdoctoral future – have also seen improvement since the last measurement. Equal treatment remains a problem Another area that has improved marginally is inequality, discrimination and harassment, although management still feels that there remains much work to do. Last year, 2016, 14.3 per cent of respondents to the survey stated that they had been subjected to such treatment at sometime during their doctoral studies (compared to 16.5 per cent during the period 2008-2012). However, considerably fewer experienced any such behaviour on the part of their own supervisor. “Green Light is a further initiative to come to grips with this,” explains Marianne Schultzberg. Equal treatment is one of the factors that Matti Nikkola, study director at the Department of Cell and Molecular Biology, would also like to see improved going forward. “KI is a university that works to improve health. We must be good at this,” Matti Nikkola says. Just like Marianne Schultzberg, Matti Nikkola considers exit polls to be a great help in this work: “KI has developed an entire toolbox to provide us with excellent support and metrics,” he says. The adoption of a four-year period allows the anonymized breakdown of the information to departmental level, so that study directors can use it to develop their own doctoral courses. Michael Fored, study director at the Department of Medicine, Solna, and a member of the Board of Research Education, sees this as an important activity.  “Educating researchers is an important task for KI. A great deal of KI’s research is carried out by doctoral candidates and sometimes a supervisor may be driven by something other than simply educating their future colleagues. For example, one can’t become a professor without first having doctoral students,” Michael Fored says. He feels that it is important to safeguard the educational component of any doctoral course, rather than viewing it as primarily a staffing issue. “We need to create a common culture and research morality for KI. Doctoral education is a good place to do so.” Text: Ulrika Fjällborg

Three researchers at Karolinska Institutet receive the maximum grant as the Swedish Cancer Society distributes 454 million kronor in research funding. In total, 83 researchers at KI receive more than SEK 180 million, of which almost SEK 73 million in new grants. Yihai Cao, professor at the Department of Microbiology, Tumor and Cell Biology, researches in tumours’ blood vessels with the aim of improving the effect of drugs that inhibit the formation of new vessels that tumours need to be able to grow. He is granted 2.25 million kronor a year for three years. Joakim Dillner, professor at the Department of Laboratory Medicine, researches in human papilloma virus, HPV, with the aim of preventing those forms of cancer that are caused by HPV by among other things optimising screening for cervical cancer. He is granted 2.25 million a year for three years.   Jussi Taipale, professor at the Department of Medical Biochemistry and Biophysics, researches in processes that control the growth of cancer cells, knowledge that in the long term might be able to be used to develop new drugs. He is granted 2.25 million a year for three years.

Times Higher Education (THE) places Karolinska Institutet at number 15 among the world’s best universities for medicine (pre-clinical, clinical studies and health sciences) in this years ranking. Among European universities, KI finished in 5th place. THE also ranks universities in the field of life science, where KI is in 25th place worldwide and 7th in Europe.   This year, THE presented a new field of psychology and here KI was ranked 19th worldwide and 3rd in Europe. “THE’s new field of psychology shows an exciting result on KI’s part, although this is a relatively small field and a longer series of results is required to better interpret the significance,” says Björn Forslöw, Controller of Operations at Karolinska Institutet.