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Pneumococci are the most common cause of respiratory tract infections, such as otitis and sinusitis, as well as of severe infections like pneumonia and meningitis. A new study from Karolinska Institutet published in Nature Microbiology shows how the bacteria can inhibit immune cell reaction and survive inside cells to give rise to pneumonia. “This is a paradigm shift that increases our understanding of how pneumococci cause disease, and might explain the long term consequences of pneumococcal infections such as for example heart disease,” says Professor Birgitta Henriques-Normark at the Department of Microbiology, Tumour and Cell Biology, Karolinska Institutet. “This is an important discovery that will lead to new strategies for tackling pneumococcal infections.” Pneumococci are found in the normal flora of healthy individuals, and up to 60 percent of pre-school children have the bacteria in their noses. Usually, these bacteria are harmless but they are also a common cause of otitis, pneumonia, septicaemia and meningitis. Globally, some two million people die from pneumococcal infections every year. To find out why the bacteria only sometimes cause disease, the researchers looked more closely at the toxin pneumolysin, which is produced by the pneumococcus. This cytolethal toxin enables pathogenic effects of the bacteria. “We made the very surprising discovery of a new property of pneumolysin,” says Professor Henriques-Normark. “We found that pneumolysin is able to interact with a special receptor, MRC-1, that is found in certain immune cells, and in so doing trigger an anti-inflammatory response.” Once inside the immune cells, the bacteria can hide from further attack and possibly even grow, to eventually give rise to pneumonia. “It has been thought that pneumolysin only induces a pro-inflammatory response, but we now show that it can also have an anti-inflammatory role” she continues. “This is because the bacteria can use pneumolysin as a means to survive the attacks of the immune system.” The study was conducted on both mouse and human cells, and when the researchers studied mice lacking the MRC-1 receptor, they observed that lower numbers of pneumococci were found in the upper respiratory tract. The researchers believe that the findings may be of importance for development of treatment and vaccines against pneumococcal infections. The research was done in collaboration with a research team at the Institute of Infection and Global Health, University of Liverpool, and with the assistance of the Science for Life Laboratory Mass Spectrometry Based Proteomics Facility in Uppsala. The Swedish arm of the research funding came from the Swedish Research Council, Stockholm County Council, the Swedish Foundation for Strategic Research (SSF) and the Knut and Alice Wallenberg Foundation. Publication ”Pneumolysin binds to the Mannose-Receptor C type 1 (MRC-1) leading to anti-inflammatory responses and enhanced pneumococcal survival”. Karthik Subramanian, Daniel R Neill, Hesham Malak, Laura Spelmink, Shadia Khandaker, Giorgia Dalla Libera Marchiori, Emma Dearing, Alun Kirby, Marie Yang, Adnane Achour, Johan Nilvebrant, Per-Åke Nygren, Laura Plant, Aras Kadioglu and Birgitta Henriques-Normark. Nature Microbiology, online 12 november 2018, doi: 10.1038/s41564-018-0280-x

Researchers at Karolinska Institutet, having compared the development of allergies in children with and without the recommended vaccinations, find no support for the claim that childhood vaccination can increase the risk of allergy. The study is published in EClinicalMedicine, a new open access journal published by The Lancet. “Even though Sweden has a high rate of childhood vaccination, there are still some parents who are uncertain about the vaccination programme out of fear that the vaccines make children ill,” says study leader Johan Alm, consultant at Sachsska Children’s Hospital and docent at Karolinska Institutet’s Department of Clinical Science and Education at Stockholm South General Hospital. “Our study is important since it gives no support to the claim that the observed increase in childhood allergies is related to vaccination.” Since most children are vaccinated according to the national vaccination program, it has been difficult to study whether there is a link between vaccination and childhood allergies. The current research has been carried out in collaboration with the Vidar Clinic in Järna, Stockholm, which enabled access to a relatively large group of children not vaccinated according to the recommendation. Earlier research has shown that, for reasons as yet unknown, children with an anthroposophic lifestyle develop fewer allergies than others. Characteristic aspects of the anthroposophic lifestyle include more home births, longer breastfeeding periods, a biodynamic/organic, largely vegetarian diet and the restrictive use of certain drugs. Many children of such families also have a more individualised vaccination programme, while some are not vaccinated at all. Children of anthroposophic families In this present study, the researchers monitored children of anthroposophic families and compared them with children from more conventional families, who normally follow the national vaccination programme. Also included was a third group of children from families with a partially anthroposophic lifestyle. All in all, the study monitored 466 children from birth to the age of five, with detailed information on the vaccines they had been given and risk factors for allergies. Blood samples were taken at the ages of six months, one, two and five years for the purpose of analysing the presence of allergy antibodies towards common foods and airborne allergens. A correlation between a low level of vaccination and a low risk of allergy was observed by the researchers, especially during the first year of life, also after having statistically controlled for socio-economic status and known risk factors for allergy. But when they also controlled for the differences related to an anthroposophic lifestyle, this correlation disappeared. The risk of allergy in 54 children who at the age of five were still completely unvaccinated was no longer any different from that in children who had had the recommended vaccinations. “Our conclusion is that there has to be something else about the anthroposophic lifestyle that causes the relatively low level of allergies,” says Dr Alm. “What this might be we don’t yet know, but it’s something we’ll be examining more closely.” Carefully monitored  The study’s strengths are that the children were carefully monitored during their early years and that a significant proportion had not been vaccinated in accordance with the regulations. One weakness is that the researchers did not study the link to actual allergies, only to a blood sample-based allergy assay. “This is an objective and generally used metric, but it is not as reliable a metric as clinically diagnosed allergies,” says Dr Alm. The study was financed from several sources, including the ALF programme, the Swedish Asthma and Allergy Association, the Cancer and Allergy Foundation, the Ekhaga Foundation, FAS/Forte, the Milk Drop Association, the Hesselman Foundation, Karolinska Institutet, the Samaritan Foundation, the TH-Berg Foundation, Thermo Fisher AB, the Swedish Research Council, the Vidar Foundation and the Vårdal Foundation. The study was based on the ALADDIN study, which was launched at Karolinska Institutet in 2004 to study possible environmental and lifestyle factors during pregnancy and childhood that impact on the development of allergies and other childhood conditions. Publication Vaccination and allergic sensitization in early childhood – the ALADDIN birth cohort Jackie Swartz, Bernice Aronsson, Frank Lindblad, Hans Järnbert-Pettersson, Annika Scheynius, Göran Pershagen, Johan Alm EClinicalMedicine, online 7 November 2018

Researchers at Karolinska Institutet have identified a protein that determines the identity and invasive properties of breast cancer cells. The finding could lead to the development of new therapeutic and diagnostic strategies to target breast cancer invasion and metastasis. The study is published in the scientific journal Cancer Research. Cancer cell invasion of the surrounding tissue is the first step in metastasis, the major cause of death in cancer. Our knowledge of how cancer cells acquire invasive and metastatic properties is incomplete and, consequently, there is a lack of treatment for cancer patients with metastatic disease. The current study sheds new light on this area. “In recent years, it has become evident that a change in a cancer cell’s identity may contribute to its invasive and metastatic behaviour,” says Jonas Fuxe, Associate Professor at the Department of Microbiology, Tumor and Cell Biology at Karolinska Institutet, who led the study. Not a solid identity For a long time, it was believed that a cell’s identity, which is created during embryonic development, is a permanent feature. Thus, once a cell has been instructed to become, for example, a muscle cell, a nerve cell or a skin cell, it will remain this type of cell, no matter what. Today, however, we know that a cell’s identity is not as solid and can change under pathological conditions such as cancer. Cancer cells mostly originate from a cell type called epithelial cells that form the skin, the inner surfaces of our tubular organs, and glands, for example in the breast. Recent studies show that breast cancer cells may lose their epithelial identity and acquire invasive and metastatic properties through a process termed epithelial-mesenchymal transition (EMT). “Induction of EMT may be described as a process resembling how boats in a harbour being unhitched from their anchoring points become ready to move out,” says Dr. Fuxe. “This is where a protein called CXADR, or CAR, comes in.” Protein with important function CAR was originally identified as a virus receptor, but its normal function has not been understood. CAR is often lost during cancer progression towards invasive and metastatic disease, but the implications of this have not been clear. “What we show in this study is that CAR is an important anchoring point for breast cancer cells, preventing them from losing their epithelial cell identity and becoming invasive,” says Dr. Fuxe. What was also interesting was that, when CAR was reintroduced into breast cancer cells with low CAR levels, it was possible to change cells back to a more epithelial (normal) identity and thereby repress their invasive properties. The results may open up the way to target CAR as a new strategy for inhibiting breast cancer invasion and metastasis. The study was conducted in Jonas Fuxe’s laboratory in collaboration with colleagues at Karolinska Institutet, and researchers at Uppsala and Umeå Universities in Sweden, and Weill Cornell Medicine in New York. The research was funded by the Swedish Cancer Society, the Swedish Research Council and Karolinska Institutet. Publication “CXADR-Mediated Formation of an AKT Inhibitory Signalosome at Tight Junctions Controls Epithelial-Mesenchymal Plasticity in Breast Cancer” Azadeh Nilchian, Joel Johansson, Aram Ghalali, Sandra Travica, Ana Santiago, Oskar Rosencrantz, Kerstin Sollerbrant, C. Theresa Vincent, Malin Sund, Ulla Stenius and Jonas Fuxe Cancer Research, online 1 November 2018, doi: 10.1158/0008-5472.CAN-18-1742

Eight professors were inaugurated, and two adjunct professors and two visiting professors were welcomed at Karolinska Institutet’s inauguration ceremony on 11 October. The Grand Silver Medal and academic distinctions were also awarded during the evening. In his speech at the inauguration ceremony, President Ole Petter Ottersen presented the university’s new vision: We are advancing knowledge about life and strive towards better health for all.. He also encouraged the new professors to spend time teaching students and to act with a clear ethical compass and critical reflection. Maria Ankarcrona, Professor of Experimental Neurogeriatrics, held a speech on behalf of the new professors and especially emphasised the education and the students: “The students ask the questions we’ve forgotten to ask – and they force us to provide answers. The students teach us a great deal,” she said. Maria Ankarcrona both studied as a doctoral student and earned her PhD with her thesis at Karolinska Institutet in 1996. The evening also highlighted the recent PhD recipient Bianca Tesi, who wrote her thesis at the Department of Women’s and Children’s Health in 2017. This year she received the Dimitris N. Chorafas Prize for the best thesis, which is awarded to promising young researchers. The eight new professors were each portrayed in their own film that was shown on a large screen in the Erling Persson Hall at Aula Medica, where the inauguration ceremony was held. In the films, the new professors spoke about their areas of research and what drives them. One was Christian Giske, Professor of Clinical Bacteriology, who played football and spoke about his area of research in the film, resistant bacteria in the intestines and how the hard-to-treat bacteria can be handled. He explained that the best in this area of research has yet to be seen. “I hope to be able to give something back to my university. This is something I’m looking forward to,” said Christian Giske as he kicked the ball into the goal. New adjunct professors and visiting professors, Georgios Rassidakis, Anna Nordenström, Mathias Uhlén and Marie Klingberg Allvin, were also welcomed to Karolinska Institutet.   Academic prizes and distinctions awarded during the inauguration ceremony Karolinska Institutet’s Grand Silver Medal 2018 to Håkan Eriksson, Laura Fratiglioni and Bertil Fredholm. Dimitris N. Chorafas Prize 2018 to Bianca Tesi. Eric K. Fernström Prize 2018 to Pernilla Lagergren. Dr. Axel Hirsch Prize 2018 to Gunnar C. Hansson. Håkan Mogren Stipend 2018 to Anders Castor. Karolinska Institutet Pedagogical Prize 2018 to Lena Nilsson-Wikmar. Lennart Nilsson Award 2018 to Thomas Deerinck. Karolinska Institutet Prize for Research in Medical Education 2018 to Lorelei Lingard.

A pilot study in which healthcare workers in the Central African Republic used a smartphone app to transmit public health disease reports to health authorities demonstrates that this technique contributes to early detection and prevention of infectious diseases and outbreaks. The study, which is an international cooperation project with researchers at Karolinska Institutet and others, is published in the scientific journal Conflict and Health. Ensuring the availability of complete, timely disease surveillance information in low-resource settings presents many challenges. In the current study healthcare workers, from 21 sentinel clinics in the province of Mambere Kadei in the Central African Republic (CAR), were trained to use a simple smartphone app solution to submit their weekly reports on 20 diseases by SMS during a 15-week period in 2016. The reports were first received by a server which consisted of a laptop with a local SIM card. They were then compiled into a database on the laptop and all data were displayed on a dashboard, including geographical information on the location of the reported diseases. If a case raised suspicions of one of the diseases, the relevant biological samples were sent to Institut Pasteur in Bangui, the capital city of CAR. The app reporting system had significant impact The results were compared to a conventional paper-based surveillance system that was used in the province the year before, and to another conventional system in an adjacent health district at the same time as the study. The app-based data transmission system more than doubled the comprehensiveness and timeliness of disease surveillance reports. “Our study shows that by using relatively low-cost and simple technology, we are able to accelerate the transmission of data from clinics to the Ministry of Health so that the Ministry can respond quickly. This is of great importance to the general public for its potential of preventing infectious diseases and outbreaks,” says Ziad El-Khatib, associate professor at the Department of Public Health Sciences at Karolinska Institutet and lead author of the study. The researchers also added costing analysis to the study, which is vital information for the possible upscaling of the project. “We managed to show that this method can be used in a tense, post-conflict, low-resource setting and infrastructure, as is the case in the Central African Republic. The province is the same size as Belgium, which makes these results interesting in the context of possible projects at national level in other countries,” says Ziad El-Khatib. The study was financed by Doctors Without Borders (MSF) and conducted by researchers at Karolinska Institutet in collaboration with MSF, the World Health Organization (WHO), the Ministry of Health of CAR and the Department of Community Health and Epidemiology, University of Saskatchewan, Canada. Publication “SMS-based smartphone application for disease surveillance has doubled completeness and timeliness in a limited-resource setting – Evaluation of a 15-week pilot program in Central African Republic (CAR)” Ziad El-Khatib, Maya Shah, Samuel N Zallappa, Pierre Nabeth, José Guerra, Daniel Dinito, Casimir T. Manengu, Michel Yao, Aline Philibert, Lazare Massina, Claes-Philip Staiger, Raphael Mbailao, Jean-Pierre Kouli, Hippolyte Mboma, Misato Assani, Geraldine Duc, Dago Inagbe, Alpha Boubaca Barry, Thierry Dumont, Philippe Cavailler, Michel Quere, Brian Willett, Souheil Reaiche, Hervé de Ribaucourt and Bruce Reeder. Conflict and Health, online 24 October, 2018, doi: 10.1186/s13031-018-0177-6

A new structure in human cells has been discovered by researchers at Karolinska Institutet in collaboration with colleagues in the UK. The structure is a new type of protein complex that the cell uses to attach to its surroundings and proves to play a key part in cell division. The study is published in the journal Nature Cell Biology. The cells in a tissue are surrounded by a net-like structure called the extracellular matrix. To attach itself to the matrix the cells have receptor molecules on their surfaces, which control the assembly of large protein complexes inside them. These so-called adhesion complexes connect the outside to the cell interior and also signal to the cell about its immediate environment, which affects its properties and behaviour.  Researchers at Karolinska Institutet have now discovered a new type of adhesion complex with a unique molecular composition that sets it apart from those already known about. The discovery has been made in collaboration with researchers in the UK. Surprising discovery “It’s incredibly surprising that there’s a new cell structure left to discover in 2018,” says principal investigator Staffan Strömblad, professor at the Department of Biosciences and Nutrition, Karolinska Institutet. “The existence of this type of adhesion complex has completely passed us by.” The newly discovered adhesion complex can provide answers to an as-yet unanswered question – how the cell can remain attached to the matrix during cell division. The previously known adhesion complexes dissolve during the process to allow the cell to divide. But not this new type. “We’ve shown that this new adhesion complex remains and attaches the cell during cell division,” says Professor Strömblad. Memory function The researchers also show that the newly discovered structures control the ability of daughter cells to occupy the right place after cell division. This memory function was interrupted when the researchers blocked the adhesion complex. The study was done on human cell lines mainly using confocal microscopy and mass spectrometry. Further research is now needed to examine the new adhesion complex in living organisms. “Our findings raise many new and important questions about the presence and function of these structures,” says Professor Strömblad. “We believe that they’re also involved in other processes than cell division, but this remains to be discovered.” The researchers call the newly discovered cell structure ‘reticular adhesions’ to reflect their net-like form. The study was financed with grants from the EU’s Seventh Framework Programme and Horizon 2020, the Swedish Foundation for Strategic Research, the Swedish Research Council, the Swedish Cancer Society and Cancer Research UK. Publication “Reticular adhesions are a distinct class of cell-matrix adhesions that mediate attachment during mitosis” John G. Lock, Matthew C. Jones, Janet A. Askari, Xiaowei Gong, Anna Oddone, Helene Olofsson, Sara Göransson, Melike Lakadamyali, Martin J. Humphries, Staffan Strömblad Nature Cell Biology, online 22 October 2018, doi: 10.1038/s41556-018-0220-2

Levels of antiphospholipid antibodies, which are associated with rheumatic diseases, are also elevated in myocardial infarction without any autoimmune co-morbidity, a study from Karolinska Institutet in Sweden published in Annals of Internal Medicine reports. Antiphospholipid antibodies (aPL) are a group of antibodies that target endogenous tissue, including the fat molecule cardiolipin and the plasma protein β2glycoprotein-I. Cardiolipin is found in the membranes of blood vessel and blood platelet cells, whereas β2glycoprotein-I is found in the blood and is thought to help the body rid itself of dead cells. The antibodies are common in rheumatic diseases such as SLE and increase the risk of blood clots. Antiphospholipid syndrome (APS) is an autoimmune condition characterised by recurrent blood clots and/or pregnancy morbidities together with chronically elevated levels of antiphospholipid antibodies. It is unknown how common the antibodies are in patients with myocardial infarction but without any autoimmune co-morbidity. Previous studies have been small and the antibody measurement flawed. “I’ve long been convinced that the antibodies are more common than we think and have now been able to analyse their presence in a large patient material,” says Elisabet Svenungsson, professor of rheumatology at Karolinska Institutet's Department of Medicine in Solna. Ten times more common in heart attacks The study involved 800 patients from 17 Swedish hospitals who had suffered their first myocardial infarction and as many matched healthy controls. Their blood was then analysed 6 to 10 weeks after the infarction for three different antiphospholipid antibody types: immunoglobulin G (IgG), M (IgM) and A (IgA). It was found that eleven per cent of the patients had antiphospholipid antibodies against both cardiolipin and β2glycoprotein-I, which was ten times more than the controls. “It was a surprisingly high proportion of the patients and the levels were also clearly high,” says Professor Svenungsson. However, the increase was only found in the IgG antibodies, the type that is considered most associated with blood clots. Can change the treatment of myocardial infarction The measurement was done on one single occasion, so it is not impossible that it reflects a temporary reaction to the infarction. However, if the levels of antiphospholipid antibodies remained elevated for a further three months, by definition these patients have APS. “In which case they should, according to current recommendations, be prescribed lifelong treatment with the anticoagulant warfarin, which reduces the risk of new blood clots,” says Elisabet Svenungsson. “This would change the prevailing guidelines for the investigation and treatment of heart attacks.” The study was conducted as a subanalysis of the PAROKRANK study in association with Uppsala University, the Royal Institute of Technology and Capio St Göran’s Hospital. It was financed by AFA Försäkring, the Swedish Heart and Lung Foundation, the Swedish Research Council, the Swedish Society of Medicine, Stockholm County Council through the ALF programme, the King Gustaf V 80-year Foundation and the Swedish Rheumatism Association. Bio-Rad contributed antibody reagents, but had no influence over the planning or execution of the study. None of the researchers have declared any commercial interests. Publication “Antiphospholipid Antibodies in Patients with Myocardial Infarction” Giorgia Grosso, Natalie Sippl, Barbro Kjellström, Khaled Amara, Ulf de Faire, Kerstin Elvin, Bertil Lindahl, Per Näsman, Lars Rydén, Anna Norhammar, Elisabet Svenungsson. Annals of Internal Medicine, online 23 October 2018, doi: 10.7326/M18-2130

The way we breathe may affect how well our memories are consolidated (i.e. reinforced and stabilised). If we breathe through the nose rather than the mouth after trying to learn a set of smells, we remember them better, researchers at Karolinska Institutet in Sweden report in The Journal of Neuroscience. Research into how breathing affects the brain has become an ever-more popular field in recent years and new methodologies have enabled more studies, many of which have concentrated on the memory. Researchers from Karolinska Institutet now show that participants who breathe through the nose consolidate their memories better. “Our study shows that we remember smells better if we breathe through the nose when the memory is being consolidated – the process that takes place between learning and memory retrieval,” says Artin Arshamian, researcher at the Department of Clinical Neuroscience, Karolinska Institutet. “This is the first time someone has demonstrated this.” One reason why this phenomenon has not previously been available for study is that the most common laboratory animals – rats and mice – cannot breathe naturally through their mouths. For the study, the researchers had participants learn twelve different smells on two separate occasions. They were then asked to either breathe through their noses or mouths for one hour. When the time was up, the participants were presented with the old as well as a new set of twelve smells, and asked to say if each one was from the learning session or new. The results showed that when the participants breathed through their noses between the time of learning and recognition, they remembered the smells better. New method facilitates measuring activity in the brain “The next step is to measure what actually happens in the brain during breathing and how this is linked to memory,” says Dr Arshamian. “This was previously a practical impossibility as electrodes had to be inserted directly into the brain. We’ve managed to get round this problem and now we’re developing, with my colleague Johan Lundström, a new means of measuring activity in the olfactory bulb and brain without having to insert electrodes.” Earlier research has shown that the receptors in the olfactory bulb detect not only smells but also variations in the airflow itself. In the different phases of inhalation and exhalation, different parts of the brain are activated. But how the synchronisation of breathing and brain activity happens and how it affects the brain and therefore our behaviour is unknown. Traditional medicine has often, however, stressed the importance of breathing. “The idea that breathing affects our behaviour is actually not new,” says Dr Arshamian. “In fact, the knowledge has been around for thousands of years in such areas as meditation. But no one has managed to prove scientifically what actually goes on in the brain. We now have tools that can reveal new clinical knowledge.” The study was financed by several bodies, including the Knut and Alice Wallenberg Foundation, the Swedish Research Council and the Netherlands Organization for Scientific Research, Ammodo Science Award. Publication “Respiration modulates olfactory memory consolidation in humans”. Artin Arshamian, Behzad Iravani, Asifa Majid and Johan N. Lundström. The Journal of Neuroscience, online 22 October 2018, doi: 10.1523/JNEUROSCI.3360-17.2018.

Children who develop inflammatory bowel disease (ulcerative colitis or Crohn’s disease) have an increased risk of death, both in childhood and later in life, a study from Karolinska Institutet published in the journal Gastroenterology reports. It is therefore important that patients who are diagnosed as children are carefully monitored, argue the researchers behind the study. The researchers identified patients with inflammatory bowel disease (IBD) such as ulcerative colitis and Crohn’s disease between the years 1964 and 2014 via the Swedish patient register. Using these data, they compared mortality rates in about 9,400 children who developed IBD with those of other children. Their results show that children who developed IBD before the age of 18 have a three to five-fold higher mortality rate than people without IBD, both during childhood and into adulthood. This translates to a 2.2-year reduction in life expectancy in individuals monitored up to the age of 65. Small differences in number of deaths “It should be remembered that we’re talking small differences in number of deaths,” explains lead author Ola Olén, consultant and researcher at Karolinska Institutet’s Department of Medicine in Solna. “Most young people with IBD do not die earlier than their peers, but a few individuals with a severe case of IBD and serious complications such as cancer greatly elevate the relative risk.” The most common cause of death was cancer, while fatalities due to IBD itself accounted for the largest relative increase in mortality. “Individuals who are diagnosed in childhood need to be monitored carefully,” says Dr Olén. “Those who might especially benefit from being closely monitored to avoid fatal intestinal cancer are children with ulcerative colitis, who also have the chronic liver disease primary sclerosing cholangitis.” Associated with cancer IBD in adults has previously been linked to shortened life expectancy. IBD is often thought to have a more aggressive disease course in children than in adults and has been associated with several types of cancer. However, it has been unclear how life expectancy is affected by childhood-onset IBD and if the mortality rate has changed since the introduction of modern drugs. “IBD therapy has improved greatly since the 1960s,” says Dr Olén. “For one thing, we often now use new types of immunomodulating drugs. However, we couldn’t see that mortality rates have gone down since their introduction.” The study was financed by the Swedish Society of Medicine, the Swedish Stomach and Bowel Association's Fund, the Jane and Dan Olsson Foundation, the Milk Drop Association, the Bengt Ihre scholarship for gastroenterological research, Karolinska Institutet’s Foundations and Funds, ALF funding, the Swedish Cancer Society, the Swedish Research Council and the Swedish Foundation for Strategic Research. Publication “Increased Mortality of Patients with Childhood-onset Inflammatory Bowel Diseases, Compared With the General Population” Ola Olén, Johan Askling, Michael Sachs, Paolo Frumento, Martin Neovius, Karin Ekström Smedby, Anders Ekbom, Petter Malmborg and Jonas F Ludvigsson Gastroenterology, online 17 October 2018, doi: 10.1053/j.gastro.2018.10.028

The launch of KI Alumni China – Karolinska Institutet’s alumni network in China – continues. During the week, members of the KI management will be attending receptions in China for some 100 alumni. Last spring, the university launched KI Alumni China, its first organised international alumni network, with an event on the Solna campus. A week of events, this time on Chinese soil, commenced on Saturday 13 October. Among other things the program includes an official ceremony to celebrate the launch of the network and to gather together KI alumni in their home nation. “This is our way of showing appreciation for KI alumni in China, who are important ambassadors for KI,” says Karin Dahlman-Wright, KI vice-president and member of the delegation. “We want to give them an opportunity to meet each other, and ourselves an opportunity to discuss topical issues with our alumni on their home ground, and find out how we can best develop the alumni role and the alumni network for the future.” She hopes that the alumni network in China will enhance KI’s profile as an internationally leading medical university that competes on the global arena for talent and resources. Reception dinners, symposia and fairs The week’s programme includes three reception dinners and symposia in Peking, Shanghai and Jinan (at Shandong University), where most alumni live. KI will also have a presence at student recruitment fairs. Amongst the non-academic participants will be representatives of Sweden’s Consulate-General in Shanghai and the Chinese Ministry of Health. “For me and other KI alumni in China, this launch week means that we now have an official KI alumni network that gives us close ties to the university, not only virtually but also face-to-face,” says Wenli “Claire” Ye, KI’s alumni ambassador in China, who studied for a master’s in Bioentrepreneurship at KI between 2008 and 2010. Today, Claire Ye is marketing and product manager at a recently opened private hospital in Shanghai. She hopes that the network will one day serve as a strong bridge linking KI, the alumni and different healthcare-related sectors of society (industry, academia, public sector). Strengthening the bond between KI and the alumni Marianne Schultzberg, dean of doctoral research at KI, is also in the delegation. She sees the event in China as an important step for strengthening the bond between KI and the alumni as future partners and doctoral supervisors. “As well as thanking them for having done their doctoral education/postdoc period at KI, we hope to find out how we can support them in their continuing careers. The alumni network is vital to KI’s doctoral education through the new China-KI doctoral students who are already being – and will continue to be – engaged in collaborations between the alumni and their former supervisors at KI, or other researchers at KI with whom they were in contact during their time with us,” she says. Networks are essential According to alumni coordinator Megan Osler, the launch event in China is a symbolically important step for KI towards meeting its internationalisation goals. “Networks are essential in our professional lives. With this official recognition, we properly celebrate the establishment of the KI alumni China network with our alumni,” she says. Also participating in the week-long event, along with several researchers, will be international coordinator Katarina Drakenberg, docent and China-coordinator Nailin Li, and KI student Chenfei “Frank” Ning.   Facts KI Alumni China There are over 200 KI alumni in China, comprising former master’s students, doctoral students, exchange students, visiting researchers, visiting professors and so forth. A digital forum on the Chinese social media platform “WeChat” called KI Alumni China currently has over 130 members.

Two researchers at Karolinska Institutet have been appointed Ragnar Söderberg Fellows in Medicine 2018. The two researchers will each receive SEK 8 million in funding from the Ragnar Söderberg Foundation. This fundning programme is aimed towards successfull young researchers early in their careers. Important assessment criterias are scientific quality and the ability to independently and successfully manage a research project and become an engaged research leader. In addition to the two Ragnar Söderberg Fellows from KI, a researcher from Lund University was appointed. The two KI researchers are:   Asghar Muhammad, Department of Medicine, Solna The project in brief: This project will investigate the extent to which infectious diseases drive cellular aging and if there is a long-term hidden cost of chronic asymptomatic infections on cellular aging in humans. The researchers will take experimental, epidemiological and cellular approaches to reach the objective. More information from the Ragnar Söderberg Foundation  (scroll down to find English version)   Armin Lak, Department of Neuroscience (not yet arrived at KI) The project in brief: Decision making concerns every aspect of our lives, from daily routines such as what to eat for lunch to more life changing occasions such as whom to marry. Despite substantial progress in understanding the psychological and computational foundations of decision making, the brain hardware, i.e. neuronal circuits, that govern choice behaviour have remained elusive. This hypothesis-driven project aims at identifying neuronal circuits that underlie our decisions. More about this project (scroll down to find English version)

In two socio-economically disadvantaged Stockholm suburbs, an urban township in South Africa and a rural area in Uganda, new methods are currently being tested to help people with type 2 diabetes take better control of their disease. The studies are part of the international research project Smart2d, which is led from Karolinska Institutet. On 17 October, a seminar day is held to share knowledge from the project. – Almost every day of the year, a person who has type 2 diabetes or is at risk of developing the disease, need to take care of himself and try to follow the advice given by the health care. Patients need a lot of support to do that, says Meena Daivadanam, researcher at the department of Public Health Science at Karolinska Institutet and senior lecturer, department of Food Studies, Nutrition and Dietetics, Uppsala University Meena Daivadanam is leading the international research project Smart2d (self-management approach and reciprocal learning for the prevention and management of type 2 diabetes), which will hold a seminar day at KI on October 17th to share knowledge and discuss subjects related to the project. The aim of Smart2d is to strengthen the individual's capacity for self-management of type 2 diabetes and for prevention of the disease. The project is funded by the EU Horizon 2020 Framework Program and is a collaboration between six academic partners in five countries, with KI as coordinating institute. Support from others is a central part of improved diabetes care In the project, self-management programs and health programs are developed and targeted at populations in three different settings where the need of improved diabetes care is big: a rural area in Uganda, an urban township in South Africa and two socio-economically vulnerable suburbs of Stockholm in Sweden. – We have deliberately chosen countries from three different income levels because it allows us to learn from each other. To find new solutions from our respective strengths and weaknesses in diabetes care in the different countries, says Meena Daivadanam. Smart2d uses strategies that have been proven effective in strengthening the healthcare system in other contexts. This is so called ”task shifting”, where some tasks are moved from, for example, physicians to nurses, and to include community networks outside the formal healthcare systems in the self-management process. This can be civil offices, voluntary organizations, associations, churches and mosques. A central part is support from other people in the form of structured support sessions in patient groups or with a mentor. The four-year project started in 2015. After the initial phase, an overall self-care program has been developed. It has then been adapted for the three different settings and is now being tested in controlled studies to investigate the effect of the programs, for example on the participants’ blood sugar levels. Collaboration towards a common goal On October 17th, Smart2d will host a seminar at KI for the projects’ stakeholders or anyone interested or interested in project’s research and experiences. The day focuses on the work in Sweden and is an opportunity for, for example, employees from participating health centers, organizations and municipalities to meet researchers from the project. The day is relevant to researchers and students interested in global health and public health, especially non-communicable diseases. Smart2d also provides examples of how collaboration between different scientific disciplines contributes to a common goal. – Not least, the day gives an opportunity to talk about challenges in implementation research, says Meena Daivadanam. – We are working in real life, with real challenges. It is exciting but also extremely challenging. This is an opportunity to discuss that, she says. Among the speakers and panelists during the day are representatives from the European Commission, the organization Global Alliance for Chronic Illnesses (GACD), participating health care centers and citizen’s offices and the Public health agency of Sweden.

Individuals with an inherited form of skin cancer often have a poor prognosis. The type of immunotherapy that was awarded this year’s Nobel Prize in Physiology or Medicine is, however, particularly effective in this patient group, research from Karolinska Institutet in Sweden shows. The study is published in the Journal of Medical Genetics. Congenital mutations of the CDKN2A gene are the strongest known risk factors for inherited skin cancer. Individuals with melanoma who carry mutations in this gene also have poor prognosis, according to previous research. Melanoma that has metastasised has a limited response to traditional chemotherapy. In recent years, new immunological treatments have appeared that many melanoma patients respond well to. These, so called immune checkpoint inhibitors treat cancer by inhibiting brake mechanisms in the immune system, a discovery by James P. Allison and Tasuku Honjo, for which they are now awarded the 2018 Nobel Prize in Physiology or Medicine. Checkpoint therapy In a new study, researchers at Karolinska Institutet and elsewhere have examined how effective immunological checkpoint therapy is for individuals with inherited CDKN2A mutation and metastatic melanoma. The results were compared with previous large-scale studies in which melanoma patients were treated with immunotherapy. “We saw that the mutation-carriers with metastatic melanoma responded surprisingly well to immunotherapy,” says study leader Hildur Helgadottir at the Department of Oncology-Pathology, Karolinska Institutet. “This is good news, particularly for this otherwise vulnerable patient group.” Almost two-thirds of the 19 patients with CDKN2A mutations included in the study responded to the treatment in a way that the tumours shrank or, as was the case in a third of the patients, disappeared completely. The expected response going by earlier studies was that just over one third would respond to the treatment and that the tumours would disappear in only one in fifteen patients. Many mutations The researchers also discovered that melanoma tumours with CDKN2A mutation had a larger number of mutations compared to tumours with no CDKN2A mutation. A possible explanation for the good therapeutic efficacy, according to the researchers, is that CDKN2A mutated tumour cells with many mutations become so unlike healthy cells that the immune system finds them easier to recognise as foreign. “Our conclusion from the study is that CDKN2A mutation carriers with metastatic melanoma have good chances of responding to immunotherapy, which can be associated with the fact that tumours with a CDKN2A mutation seem to have a tendency to accrue even more mutations, although this relationship requires further investigation,” says Dr Helgadottir. The study was made in cooperation with researchers at Lund University and Gothenburg University in Sweden and researchers in Leiden in Holland, Genua in Italy, Barcelona in Spain and Sidney in Australia. The research was financed by Iris, the Stig and Gerry Castenbäck Foundation for Cancer Research, the Swedish Cancer Society, the Swedish Society for Medical Research (SSMF), the Swedish Research Council, the ALF programme between KI and Stockholm County Council, the Dutch Cancer Society, the Italian Association for Cancer Research, the Italian Ministry of Health, the Spanish Fondo de Investigaciones Sanitarias and Instituto de Salud Carlos III, and the European Development Regional Fund. Publication “Efficacy of novel immunotherapy regimens in metastatic melanoma patients with germline CDKN2A mutations” Hildur Helgadottir, Paola Ghiorzo, Remco van Doorn, Susana Puig, Max Levin, Richard Kefford, Martin Lauss, Paola Queirolo, Lorenza Pastorino, Ellen Kapiteijn, Míriam Potrony Mateu, Cristina Carrera, Håkan Olsson, Veronica Höiom, Göran Jönsson Journal of Medical Genetics, online 5 October 2018, doi:10.1136/jmedgenet-2018-105610

The university stands steady among the top 100 in the annual ranking of the world’s universities, irrespective of orientation, conducted by Times Higher Education (THE). Among the universities in the Nordic countries Karolinska Institutet is in first place. Karolinska Institutet is in 40th place in the annual ranking of the world’s universities, regardless of orientation, conducted by Times Higher Education (THE) in Great Britain.   “This can be seen as a steady development compared to last year’s equal 38th place,” says Peter Brandberg, Operations Controller at KI. Uppsala and Lund also in the top 100 This year's THE ranking covers over 1,250 universities. Great Britain’s University of Oxford and University of Cambridge top the list. In addition to KI two other Swedish universities also make the top 100 list: Uppsala University in 87th place compared to 86th last year and Lund University in 98th place compared to 93rd last year.  Among European universities KI ranks 11th, which is on a par with last year’s equal 10th place. Among universities in Sweden and the Nordic countries KI is in first place. Higher place in the THE ranking Peter Brandberg observes that KI’s place in the THE ranking is slightly higher than in other world rankings. The Academic Ranking of World Universities was also published earlier this year, where KI retained 44th place compared to the previous ranking. “How KI performs in the world rankings is interesting but more important is the comparison within medicine and health, where KI has most of its education and research,” he says. THE’s ranking of universities in specific subject areas is as a rule published a few weeks after the general ranking.

The Royal Swedish Academy of Sciences has elected two new members – both from Karolinska Institutet. Birgitta Henriques Normark, a professor at the Department of Microbiology, Tumor and Cell Biology, has been elected to the Class for Medical Sciences. Emily Holmes, a professor at the Department of Clinical Neuroscience, has been elected to the Class for Social Sciences. Birgitta Henriques Normark conducts research in the field of experimental and clinical infection biology. An overriding theme of her work is the study of pneumococci, bacteria that can cause, e.g., ear infections, pneumonia and meningitis. Pneumococci are found in the normal flora of healthy people. One key issue is the identification of the mechanisms that cause them to result in serious infections in certain cases. Another goal is to determine how new strains form and become resistant to antibiotics. Birgitta Henriques Normark also conducts national surveillance of severe pneumococcal infections and monitors the effects of the introduction of a pneumococcal vaccine into the Swedish vaccination program. Birgitta Henriques Normark is a senior physician and in 2017 she was named as a Wallenberg Clinical Scholar. Emily Holmes’ research focuses on how advances in basic research can be used to develop and improve psychological treatment methods. She is specifically focused on how we think and remember in images, and how understanding the manner in which mental images function can allow us to develop new and more effective treatments. Her research has shown that mental images and visual thinking play an important role in psychological illnesses such as post-traumatic stress disorder (PTSD). Emily Holmes also works with the prevention of mental illness, including by investigating whether early interventions conducted in connection with emergency care can prevent the development of intrusive, unpleasant visual memories in people who have experienced traumatic events. Emily Holmes is also a visiting professor at the Department of Psychiatry at the University of Oxford. The Royal Swedish Academy of Sciences was founded in 1739 and is an independent, private organization whose overall objective is to promote the sciences and to advance their influence in society.

The presence of the human high-risk papillomavirus (HPV) in the diagnosis of invasive cervical cancer is linked to a greatly improved prognosis compared with if high-risk HPV cannot be identified in the tumour, researchers at Karolinska Institutet report in the scientific journal PLOS Medicine. The researchers believe that high-risk HPV can be another important prognostic marker that can inform the choice of therapeutic strategy. High-risk human papillomavirus (hrHPV) is the leading cause of cervical cancer. However, whether the presence of hrHPV in the tumour tissue is of significance to the prognosis has been unclear. In this present study, researchers at Karolinska Institutet have therefore looked into a possible correlation between the presence of hrHPV in the tumour and survival rates for invasive cervical cancer (i.e. cervical cancer that has spread to surrounding tissues). The researchers gathered information on all cases of invasive cervical cancer in Sweden between the years 2002 and 2011 (4,254 confirmed cases in total). They then collected HPV data from the regional biobanks for 2,845 of these women and compared survival data from national registers. Lower risk of dying Their results show that the five-year relative survival rate for women with hrHPV-positive tumours was 74 per cent compared with the female population of the same age and during the same calendar year, while it was only 54 per cent for women with hrHPV-negative tumours. HrHPV could be identified in just over 80 per cent of the tumours. Women with hrHPV-positive tumours were more likely to be discovered through screening, were younger and had a high socioeconomic status. They were also discovered at an earlier clinical stage than women with hrHPV-negative tumours. After having controlled for age, tumour type, tumour stage at diagnosis and educational background, the researchers found, however, that women with hrHPV-positive tumours still had a much lower risk of dying than the women with hrHPV-negative tumours. Could be a useful complement “The presence of hrHPV in invasive tumour tissue is thus a strong and yet routinely accessible prognostic biomarker for the prognosis of invasive cervical cancer and could be a useful complement to the established prognostic tools currently in use,” says co-author Pär Sparén, professor at the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet. The underlying biological mechanisms for why the lack of detectable hrHPV in the tumour gives a much worse prognosis are unknown and need to be interrogated further. The study was financed by the Swedish Foundation for Strategic Research, the Swedish Cancer Society, the Swedish Research Council and the China Scholarship Council. Co-author Joakim Dillner has received grants from Roche and Genomica for research on the HPV test. Bengt Andrae was a member of the National Board of Health and Welfare’s expert panel on HPV-based screening for cervical cancer in 2015. Publication “High-risk human papillomavirus status and prognosis in invasive cervical cancer: A nationwide cohort study” Jiayao Lei, Alexander Ploner, Camilla Lagheden, Carina Eklund, Sara Nordqvist Kleppe, Bengt Andrae, K. Miriam Elfström, Joakim Dillner, Pär Sparén, Karin Sundström PLOS Medicine, online 1 October 2018, doi: 10.1371/journal.pmed.1002666

This year’s Nobel Prize in Physiology or Medicine recognizes the discovery that it is possible to treat cancer by inhibiting the brakes on the immune system. Behind their discovery lies a bold idea and eager basic research, which has led to an entirely new principle for cancer therapy and new medicines that have already been approved. Many factors contribute to rapid developments in this field—in particular, current research at Karolinska Institutet. Before motion cameras and rows of seats filled with journalists from all over the world, it was announced that the 2018 Nobel Prize in Physiology or Medicine will be shared by the researchers James P. Allison and Tasuku Honjo. “For their discovery of cancer therapy by inhibition of negative immune regulation,” Secretary to the Nobel Assembly and the Nobel Committee at Karolinska Institutet Thomas Perlmann proclaimed. This year’s Prize is a recognition of the discovery that it is possible to unleash the body’s native ability to attack tumor cells by blocking mechanisms that function as a brake on the immune system By inhibiting proteins that impede the immune system’s T-cells, the T-cells can instead be activated and create an immune response to the cancer cells. New concept for cancer treatment “The discoveries made by these two researchers have led to an entirely new principle for cancer therapy,” Chair of the Nobel Committee at Karolinska Institutet Anna Wedell remarks. “Because this new cancer therapy exploits the immune system’s innate ability to attack cancer cells more broadly, this ends up being a general form of cancer therapy; not one used only on specific tumors. It will be effective in treating types of cancer we haven’t been able to treat, and provide healing to patient groups we haven’t been able to help,” Anna Wedell says. During the 1990s, James P. Allison, one of the two laureates, studied the CTLA-4 protein that is found on the surface of T-cells. The protein had earlier been found to have a suppressing function on T-cells, thus inhibiting activation of the immune system. But while other researchers tried to exploit this mechanism to treat auto-immune diseases, James P. Allison explored the alternative. Rather than seeking to inhibit activation of the immune system, Allison tried instead to block the CTLA-4 “brake” using an antibody. This freed the T-cells to attack cancer cells. “It was his idea. He was creative and bold, driving his research forward to achieve this result,” Anna Wedell says. Immune therapy inhibition In December 1994, James Allison and his colleagues completed an experimental critical to his later discovery in which an antibody to CTLA-4 was tested on mice with cancer. The result was spectacular: Nobel Committee member Klas Kärre remarked. “The mice who were treated with the antibody were cured of cancer, while the control group of mice developed large tumors. That was the beginning of a whole new field within immunotherapy, today often called “Immune Therapy Inhibition,” he says. On the basis of these results, James Allison wanted to take next steps toward human trials but was turned down by several pharmaceutical companies. Finally, a small company responded and in 2010 he published a study that showed positive results in patients with advanced skin cancer. In several of the patients, the cancer appeared to have disappeared; this result had never been seen before. In 2011, the medicine was approved by the Federal Drug Administration (FDA). The second Nobel laureate, Tasuko Honjo, had, several years before James P. Allison’s discovery, discovered another protein which also was found on the surface of T-cells. He called this protein, PD-1, and started an ambitious research program to identify its function. “This is a great example of how curiosity drives foundational research which in turn provides a significant clinical benefit. Tasuko was curious about the new molecule he had discovered, this drove his efforts to gain an understanding of its function,” Anna Wedell says. It turned out that PD-1 also functions as a brake on the immune system, but with a different mode of action than CTLA-4. Here too antibodies develop that inhibit the protein. During 2012 clinical studies showed very good results after treatment of several different cancer types. In 2014, the therapy was approved for skin cancer and in 2015 for lung cancer and kidney cancer. PD-1 inhibition is a growing field with other PD-1 inhibitors shown to be effective in treating additional forms of cancer. Significant importance As with other cancer therapies, this type of treatment can have side effects, but these are in general manageable. All patients do not show a positive effect from checkpoint inhibition, but for those who do, the difference can be significant. For example, a third of patients with skin cancer respond to CTLA-4 inhibition therapy and 20% of this number appear to have been cured when seen in a 10-year perspective. “This can seem like a modest result, but is significant when compared to earlier when all patients died after just a few years. With PD-1 inhibition 40 percent of patients with advanced metastatic melanoma are cured,” Klas Kärre says. After James P. Allison’s and Tasuku Honjo’s discoveries, there has been rapid advancement in this field of research. A large number of clinical studies are currently in progress where checkpoint treatment is being tested on a variety of cancer types. New checkpoint molecules are also being tested as targets for treatment. Attempting to combine different checkpoint inhibitors with each other is also an important way forward that may yield an even better effect—something already seen with skin cancer. Another prospect is to combine checkpoint inhibition therapy with conventional courses of treatment. Karolinska Institutet has, together with other research institutions, been a site for this research. Here researchers have participated in clinical studies to test the effect of checkpoint inhibitors on a number of different cancers. “We both participate in extensive studies run by others and design our own. My research group is planning to start its own study soon to test the effect of adding checkpoint inhibitors to existing therapies for breast cancer,” says Jonas Bergh, Professor at the Institute for Oncology and Pathology at Karolinska Instittutet. Text: Sara Nilsson

Around 50 researchers from Karolinska Iinstitutet met about 4,000 high school students when they participated in European Researchers' Night on the 28 September. The students participated in interactive activities, shows, lectures and research dialogues and more. In addition to KI, researchers from KTH and Stockholm University and others participated in the exhibition, which was performed at Alba Nova University Center at KTH. During the day Researchers’ Grand Prix was also held, where scientists compete in presenting their research as entertaining and informative as possible during four minutes. The audience of approximately 260 students voted together with a jury for the winner. In this year's competition, researchers Tobias Alfvén and Charlotte Skoglund from KI participated and finished in an honorary second and third place. The EU-event European Researchers' Night in Stockholm is organized by Vetenskapens hus. Co-organizers are Karolinska Institutet, KTH and Stockholm University. It has been organized since 2006.

Researchers at Karolinska Institutet have discovered a new way in which nerve cells can control movement. In a study on zebrafish published in the journal PNAS they show that the contact between neurons and muscles is more dynamic than previously thought. The results can open up new avenues to treating spinal cord injury and certain neurological diseases. The ability to move deliberately is essential to the survival of all animal life, and is based on an interaction between the muscles and the brain. The site where motor neurons and muscle cells communicate with each other is called the neuromuscular junction. This is where the neurons transfer signal substances that can be taken up by the muscle cells to make them contract. This point of contact – the synapse – has long been described as a relatively simple system in adult vertebrates, with the molecule acetylcholine as the most important neurotransmitter. Despite this, knowledge is lacking on how the communication is actually effected and how adult motor neurons can respond to damage or environmental change. Fine motor adjustment Researchers at Karolinska Institutet have now generated new knowledge about how the neuromuscular junction works. Their results show that it is a more dynamic system than previously believed. “Our study shows that the function of the neuromuscular synapses can change under certain conditions and in certain diseases in order to fine-tune movements, which was a completely unexpected finding,” says assistant professor Konstantinos Ampatzis at the Department of Neuroscience, Karolinska Institutet, who led the study. The study was conducted on zebrafish, which is a common model system in neurobiological research. The researchers show that changes in the form of an increase in physical activity and spinal damage can cause certain adult motor neurons to switch from producing acetylcholine to producing another neurotransmitter – glutamate. The researchers believe that this is to control movements better. New therapeutic potential The results indicate that more detailed studies of the neuromuscular junction are needed, not least in humans. Such knowledge is important because impaired communication between neurons and muscles can cause serious diseases, such as the neuromuscular disease myasthenia gravis. “Our study can open new doors to the treatment of diseases involving reduced neuromuscular transmission,” says Dr Ampatzis. “More detailed knowledge on which neurons express specific neurotransmitters can enable the development of better treatments that restore function to the nervous system.” There is also growing evidence that the neuromuscular junction is involved in the early stages of such diseases as spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS), which have previously been regarded as diseases of the motor neurons. The study was financed by the Swedish Research Council, the Strategic Research Area Neuroscience, the Swedish Brain Foundation, the Längman Cultural Foundation and Erik and Edith Fernström Foundation. Publication “Adult spinal motoneurons change their neurotransmitter phenotype to control locomotion” Maria Bertuzzi, Weipang Chang, Konstantinos Ampatzis PNAS, online 1 October 2018, doi: 10.1073/pnas.1809050115

The Knut and Alice Wallenberg Foundation (KAW) has awarded a total of SEK 104.2 million to four research projects led from Karolinska Institutet. In all, the Foundation is granting SEK 640 million this year to 22 research projects at Swedish universities. The KAW Foundation is financing research projects in the fields of medicine, science and technology that are considered to offer potential for future scientific breakthroughs. KAW is the largest private research funder in Sweden. “These grants have been awarded to promising and exciting projects at the forefront of international research, comments KAW chairperson Peter Wallenberg Jr in a press release. “The Foundation supports long-term basic research that benefits Sweden, and gives researchers complete freedom to formulate and test their hypotheses. Funding applications are evaluated by the foremost international researchers in each field,” Some other examples of project goals are: better cancer therapies, new knowledge about carbon dioxide in the atmosphere, how our seas may be impacted by future environmental changes, increasing fiber-optic capacity, and clues about how the brain can repair itself. Unveil the dynamics of cell turnover in heart and brain Project:  Cell turnover in human health and disease Grant: SEK 40,600,000 over five years Principal investigator: Professor Jonas Frisén, Department of Cell and Molecular Biology, Karolinska Institutet. Partners: Henrik Druid, Karolinska Institutet, Joakim Lundberg, KTH, and Göran Possnert, Uppsala University. Short summary: By combining a retrospective birth-dating by analysis of 14C, derived from nuclear bomb tests, with phylogeny by single-cell DNA sequencing, the researchers aim to unveil the dynamics of cell turnover, the origin of new cells and how turnover and cell lineages are altered in pathology in humans. This fundamental knowledge is needed to understand human tissue homeostasis and pathology, and to devise regenerative strategies. Destructive interaction on the way to type 2 diabetes Project: Tissue-crosstalk and metabolic regulation of type 2 diabetes Grant: SEK 18,000,000 over three years, with the possibility of a two year extension. Principal investigator: Professor Juleen Zierath, Department of Molecular Medicine and Surgery, Karolinska Institutet. Partners: Per-Olof Berggren, Carsten Daub, Anna Krook, Erik Näslund och Mikael Rydén, all at Karolinska Institutet, and Thomas Moritz, Swedish University of Agricultural Sciences.  Short summary:  Metabolism in adipose tissue, liver and skeletal muscle plays a major role in the onset of type 2 diabetes, and low-grade chronic inflammation is common in people who develop the disease.  So, how do these organs interact with each other in an inflammatory environment, and how are the insulin-producing beta cells affected? This is what the researchers in the current project will investigate and try to explain. The researchers aim to show which proteins and metabolites that are secreted from adipose tissue, liver and skeletal muscle in inflammation, how these substances affect the interaction between these organs – and how this in turn affects the insulin-producing beta cells. Walk or run – how do muscles get their commands about speed? Project: Decoding the logic of the neural circuits for motor actions Grant: SEK 16,200,000 over five years Principal investigator: Professor Abdel El Manira, Department of Neuroscience, Karolinska Institutet. Short summary: Whether moving slowly to approach a prey or quickly to escape from a predator, it is vital that our muscles move with the right timing and at the appropriate speed – but how is this achieved within neural circuits in our brain? This will be investigated in this project using both optogenetics and advanced electrophysiological approaches to map the dynamic connectivity scheme of circuits for motor actions in zebrafish. The project is expected to provide novel insights into the rules governing the organization and function of the neural circuits controlling our movements. Capturing the riddle of conception on picture Project: Integrative structural biology of mammalian fertilization: Unveiling the beginning of life from gametes to atoms Grant: SEK 29,400,000 over five years Principal investigator: Professor Luca Jovine, Department of Biosciences and Nutrition, Karolinska Institutet Partners: Alexey Amunts, Stockholm University, and Linda Sandblad, Umeå University, both also at SciLifeLab. Short summary: The goal of the project is to visualize in three dimensions how egg and sperm interact with each other and eventually fuse at the molecular level. The researchers will study different stages of mammalian fertilization and, by combining X-ray crystallography with single-particle cryo-electron microscopy as well as focused ion beam milling coupled to cryo-electron tomography, obtain information at different levels of organization – from single molecules to sections of whole gametes frozen in in near-native conditions.