Integrative Molecular Phenotyping

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Updated: 1 hour 16 min ago

Erik Norberg is awarded the Malin and Lennart Philipson Foundation Prize 2015

Thu, 20/08/2015 - 11:11
Erik Norberg at the Institute of Environmental Medicine, Karolinska Institutet, is awarded the Malin and Lennart Philipson Foundation prize 2015 for his “interesting and creative studies of alternations in the metabolism in cancer cells”. The prize is awarded in alternate years at Uppsala University and Karolinska Institutet respectively. Erik Norberg receives a grant sum of SEK 1 million per year for two years, including a personal prize during the first year of SEK 50,000. Apart from the researcher’s scientific merits, the award also recognises the ability as a leader to establish a strong research group. After receiving his Ph.D. in Medical Sciences from Karolinska Institutet in 2011, Erik Norberg joined the Dana-Farber Cancer Institute, Harvard Medical School in the USA, for his Postdoctoral studies. In 2014, he returned to Sweden and Karolinska Institutet to establish his own independent research group. His research focuses on identifying and targeting tumor specific alterations in metabolism. Read more on the Malin and Lennart Philipson Foundation website and on  

Karolinska Institutet in place 48 in new world ranking

Mon, 17/08/2015 - 09:09
The 2015 Academic Ranking of World Universities, the Shanghai ranking, shows that Karolinska Institutet remains well placed, this year as number 48, ranking the highest among the Swedish universities. The five most highly ranked universities are Harvard University, Stanford University and Massachusetts Institute of Technology. In the field of Clinical Medicine and Pharmacy KI is number 12 in the world and number 3 in Europe. More about rankings at      

Choice of method in attempted suicides reflects risk of subsequent suicide

Wed, 05/08/2015 - 09:09
The risk of completed suicide is high among people with previous attempts, particularly during the first few years after the attempt. In a study, researchers at Karolinska Institutet have shown how the method used for the attempt plays a role in the risk of a subsequent suicide death. Some psychiatric diagnoses also entail an increased risk. The study is published in the Journal of Clinical Psychiatry. Using the Swedish Board of Health and Welfare's Inpatient Register, researchers have identified 34,219 people who received care as hospital in-patients for at least one day for deliberate self-harm between 2000 and 2005. The patients were monitored until 2009 via the Board of Health and Welfare's causes of death register, i.e. between three and nine years after the suicide attempt. In 2009, 1,182 of the people in the study had died from suicide. The researchers studied the psychiatric diagnoses that patients had at the time of making their suicide attempt. They also took a closer look at the methods they used and, using this information, identified which patients with a previous suicide attempt ran the highest risk of a completed suicide. The study has yielded several clear results: attempters who used another method than poisoning, such as hanging, strangulation, asphyxiation, drowning, using a firearm, knife or other sharp instrument or jumping from a great height, ran a much higher risk of taking their own lives in the near future. Certain differences between genders were observed, particularly when it came to the use of firearms. The risk of subsequent suicide was higher among men with a previous attempt than women. The risk of subsquent suicide was also much higher in people who had been diagnosed with bipolar disorder, depression or psychosis at the time of the attempt. This applied to both men and women. Bipolar disorder was formerly called manic depression, a condition where the person shifts between depressiveness and feelings of elation. Examples of psychoses include schizophrenia, paranoid psychosis and other conditions that alter your perception of reality. When the researchers weighed these parameters together, it turned out that one in five, or 20.4 percent, of bipolar disorder patients who chose a different method to attempt suicide than poisoning had died from suicide by the end of 2009. For patients who had some form of psychosis, the corresponding figure was 15.6 percent, while for those with depression the figure was 13.9 percent. The results confirm the findings of previous long-term studies. Those studies, however, did not include patients who were treated with today's psychiatric methods. Those in the previous studies had received care for attempted suicide further back in time. The study currently being published therefore provides an up-to-date picture of patient groups. “There is a high risk of suicide after an attempt has been made, but the risk is particularly high for certain people. These patients should be treated adequately according to their underlying illness and they should be offered psychosocial support, especially in the period immediately following a suicide attempt. Mobile emergency teams are one example of this type of support. There is also reason to believe that the psychosis and bipolar treatment centres that exist or are being built in most county councils can play a significant role in reducing the suicide rate in these groups,” says Bo Runeson, Chief Physician in Psychiatry and Professor at the Department of Clinical Neuroscience at Karolinska Institutet. The research is funded by Stockholm County Council, Karolinska Institutet, Söderström-Königska Foundation and the Foundation for Professor Bror Gadelius' Memorial Fund. Publication Suicide after previous non-fatal self-harm: National cohort study 2000 – 2008 Bo Runeson, Axel Haglund, Paul Lichtenstein and Dag Tidemalm, Journal of Clinical Psychiatry, 4 August, DOI:10.4088/JSC.14m09453

New treatment principle for tuberculosis activates the body's own defence system

Wed, 29/07/2015 - 11:11
According to a new study from Karolinska Institutet which is being published in the journal Autophagy, the body's own defence system can be strengthened with existing medicines used for treating tuberculosis. The results suggest a new treatment principle for infectious diseases that can strengthen the effect of traditional antibiotic treatments and reduce the risk of developing a resistance. Widespread resistance to antibiotics requires new, expensive medicines with various side-effects to be used against tubercle bacteria. However, many affected countries lack access to such medicines. Researchers are therefore trying to develop new strategies for  effective treatment of tuberculosis, which continues to be a major worldwide problem. The researchers behind the new study are investigating how to activate the body's own antibiotics, antimicrobial peptides, which form a part of the innate immune defence system. The peptides are produced in all mucus membranes and also in granulocytes and macrophages, two types of white blood cells that are recruited to the site of infection. “We have focused particularly on increasing the body's production of the body's own peptides with the help of existing drugs. LL-37, a human antimicrobial peptide that we discovered in 1995, is highly effective against TB bacteria,” says Birgitta Agerberth at the Department of Laboratory Medicine at Karolinska Institutet, one of the researchers who has led the study. Researchers have already shown that the drugs vitamin D and phenylbutyrate increase the production of LL-37. They have now demonstrated that LL-37 plays a key role in the manner in which these drugs kill the TB bacteria. It is already known that vitamin D can trigger a process known as autophagy which is important for killing pathogenic bacteria  inside macrophages and other cells. In this study, researchers have shown that phenylbutyrate also activates autophagy   and that  vitamin D and phenylbutyrate  work even more effectively when used in combination. In addition,  the underlying mechanism of the activation has been clarified. In an another study from the same research group it is  shown that supplementary treatment with phenylbutyrate and vitamin D had positive results when combined with standard antibiotics in the treatment of newly diagnosed tuberculosis patients in Dhaka, Bangladesh. “The results show that we can thus strengthen the body's defence against serious infections such as tuberculosis by increasing the production of antimicrobial peptides. Both these studies provide combined support for a new treatment principle for infectious diseases with the activation of the body's own defence system combined with traditional antibiotic treatments. This new treatment strategy as we name “Host-Directed Therapy” has many advantages: it minimise the risk of developing resistance, it strengthens the effect of regular antibiotics and controls the often damaging inflammation that occurs commonly in different infections,” says Birgitta Agerberth. The research is funded by the Swedish Foundation for Strategic Research, Swedish Heart-Lung Foundation, the Swedish Research Council and SIDA, among others. Publication Phenylbutyrate induces LL-37-dependent autophagy and intracellular killing of Mycobacterium tuberculosis in human macrophages Rokeya Sultana Rekha, SSV Jagadeeswararao Muvva, Min Wan, Rubhana Raqib, Peter Bergman, Susanna Brighenti, Gudmundur H. Gudmundsson, Birgitta Agerberth Autophagy, online 29 July 2015, doi:10.1080/15548627.2015.1075110

Fats from fish and vegetables may increase longevity

Tue, 28/07/2015 - 08:08
A study that included more than 4,000 Swedish 60-year-olds, showed that high levels of polyunsaturated fats in the blood are linked to increased longevity and decreased risk of cardiovascular disease. The study was a collaboration between Karolinska Institutet and Uppsala University and was published in the medical journal Circulation.  In most studies that investigate the correlation between food and longevity, the subjects report what they have eaten, and this may be inaccurate. In the current study, the level of polyunsaturated fats in the blood of the subjects was measured. This has previously been shown to be a good indicator of intake of these fats that are abundant in oily fishes such as salmon and herring, as well as in walnuts, avocado and olives. “This is the world's largest study in the area as far as we know, and one of its strengths is that both men and women were evaluated at the same time”, says Professor Mai-Lis Hellénius at the Department of Medicine, Solna, Karolinska Institutet, one of the researchers in this study. The results show that high levels of polyunsaturated fats in the blood are associated with decreased overall mortality in both men and women. In women, polyunsaturated fat intake was also linked to a decreased risk of cardiovascular disease. When the results were calculated, other important lifestyle factors, such as exercise alcohol and smoking, were also taken into account. ­“The findings are clinically relevant and support current dietary guidelines that advise us to shift from saturated to unsaturated fats”, says Mai-Lis Hellénius. Publication Polyunsaturated Fat Intake Estimated by Circulating Biomarkers and Risk of Cardiovascular Disease and All-Cause Mortality in a Population-Based Cohort of 60-Year-Old Men and Women Marklund M, Leander K, Vikström M, Laguzzi F, Gigante B, Sjögren P, Cederholm T, de Faire U, Hellénius ML, Risérus U Circulation 17 June 2015, doi: 10.1161/CIRCULATIONAHA.115.015607 Text: Jenny Tollet

Brain structure reveals ability to regulate emotions

Fri, 24/07/2015 - 14:14
People diagnosed with a personality disorder may find it difficult to function in society due to difficulties in regulating emotions – but also healthy individuals differ in how often they become irritated, angry or sad. Scientists from Karolinska Institutet have published a study in the medical journal Social Cognitive and Affective Neuroscience, where they show that the affected brain areas in people with a clinical diagnosis are also affected in healthy individuals. We all vary in how often we become happy, sad or angry, and also in how strongly these emotions are expressed. This variability is a part of our personality and can be seen as a positive aspect that increases diversity in society. However, there are people that find it so difficult to regulate their emotions that it has a serious impact on their work, family and social life. These individuals may be given an emotional instability diagnosis such as borderline personality disorder or antisocial personality disorder.  Previous studies have shown that people diagnosed with emotional instability disorders exhibit a decrease in the volume of certain brain areas. The scientists wanted to know if these areas are also associated with the variability in the ability to regulate emotions that can be seen in healthy individuals. In the current study, 87 healthy subjects were given a clinical questionnaire and asked to rate to what degree they have problems with regulating emotions in their everyday lives. The brains of the subjects were then scanned with MRI. The scientists found that an area in the lower frontal lobe, the so-called orbitofrontal cortex, exhibited smaller volumes in the healthy individuals that reported that they have problems with regulating emotions. The greater the problems, the smaller the volume detected. The same area is known to have a smaller volume in patients with borderline personality disorder and antisocial personality disorder. Similar findings were also seen in other areas of the brain that are known for being important in emotional regulation. ­“The results support the idea that there is a continuum in our ability to regulate emotions, and if you are at the extreme end of the spectrum, you are likely to have problems with functioning in society and this leads to a psychiatric diagnosis”, says Associate Professor Predrag Petrovic, first author of the study and researcher at the Department of Clinical Neuroscience, Karolinska Institutet. “According to this idea, such disorders should not be seen as categorical, that you either have the condition or not. It should rather be seen as an extreme variant in the normal variability of the population”. Publication Significant grey matter changes in a region of the orbitofrontal cortex in healthy participants predicts emotional dysregulation Predrag Petrovic, Carl Johan Ekman, Johanna Klahr, Lars Tigerström, Göran Rydén, Anette G. M. Johansson, Carl Sellgren, Armita Golkar, Andreas Olsson, Arne Öhman, Martin Ingvar and Mikael Landén Social Cognitive and Affective Neuroscience, online: 15 juni 2015, doi: 10.1093/scan/nsv072. Text: Jenny Tollet

Contest a hub for future scientists

Fri, 24/07/2015 - 13:13
Set up a lab, deal with finances, plan, execute and analyze science and in an interesting way communicate the results. This is what students from Karolinska Institutet are dealing with this summer. The International Genetically Engineered Machines (iGEM) is a contest that will prepare the participants early on for a future career in science. A Stockholm team is now battling for the title in The International Genetically Engineered Machines competition (iGEM), a contest where students within the field of synthetic biology will construct their own biological system and in different ways incorporate them into living cells. iGEM, which started in 2004, this year includes a record of 281 teams worldwide. Different components such as science, innovation and scientific communication are all part of the competition. The initiative was founded at Massachusetts Institute of Technology and has now become a part of the education for engaged students at Karolinska Institutet. Felix Richter is hopeful because his 18-person team with students from KI and KTH Royal Institute of Technology in Stockholm have developed a system that will allow cells to show when they are exposed to an antigen, i.e., something that will trigger an immunological reaction. “In our project, Affibody-Based Bacterial Biomarker Assay, we use bacteria that sense the antigen and then mass produce a light signal. Now all team members have learned the techniques and next week we will see if our system really works.” The competition lasts all summer and the winners are presented at a science conference in Boston later this fall, but until then there is a lot of activity. This weekend KI students, together with students from Uppsala, are hosting a conference with the Nordic teams present. “The possibility to “take over a lab” and work on our own is invaluable in itself, but then there is also a lot of practice in communication, primarily within the teams but also between the teams, which increases the individual social competence and helps in getting new perspectives. As of today we have fruitful collaborations with teams from, e.g., Germany, France, Finland, Israel and Taiwan.” Felix Richter points out that his team is developed and run by the students themselves. Supervisors are in place but it is this young generation of scientists-to-be that get all the responsibility, from the primary idea all the way to the presentation in Boston. “We take responsibility both in success as well as failure. This is a step in the right direction for modern education and I hope it will be a permanent feature for interested students at KI.” The students have gotten financial support from The Board of Research and The Board of Doctoral Education at KI.  “This way, the individual student gets to practice for a future career in science. It is also a good way to increase internationalization, initiate entrepreneurship and stimulate a way of thinking scientifically during the students’ undergraduate studies. We are very proud of these industrious students,” says Maria G. Masucci, Deputy Vice-Chancellor for International Affairs at Karolinska Institutet.  Text: Frida Wennerholm

3D ‘printouts’ at the nanoscale using self-assembling DNA structures

Thu, 23/07/2015 - 08:08
A novel way of making 3D nanostructures from DNA is described in a study published in the renowned journal Nature. The study was led by researchers at Karolinska Institutet who collaborated with a group at Finland's Aalto University. The new technique makes it possible to synthesize 3D DNA origami structures that are also able to tolerate the low salt concentrations inside the body, which opens the way for completely new biological applications of DNA nanotechnology. The design process is also highly automated, which enables the creation of synthetic DNA nanostructures of remarkable complexity. The team behind the study likens the new approach to a 3D printer for nanoscale structures. The user draws the desired structure, in the form of a polygon object, in 3D software normally used for computer-aided design or animation. Graph-theoretic algorithms and optimization techniques are then used to calculate the DNA sequences needed to produce the structure. When the synthesized DNA sequences are combined in a salt solution, they assemble themselves into the correct structure. One of the big advantages of building nanostructures out of DNA is that the bases bind to each other through base-paring in a predictable fashion. “This new method makes it very easy to design DNA nanostructures and gives more design freedom,” says study leader Björn Högberg from the Department of Medical Biochemistry and Biophysics at Karolinska Institutet. “We can now make structures that were impossible to design previously and we can do it in the same way as one might draw a 3D structure for printing out in macroscopic scale, but instead of making it out of plastic, we print it in DNA at the nanoscale.” Using this technique, the team has built a ball, spiral, rod and bottle-shaped structure, and a DNA printout of the so-called Stanford Bunny, which is a common test model for 3D modelling. Apart from being simpler compared to former ways of making DNA origami, the method – importantly – does not require high concentrations of magnesium salt. “For biological applications, the most crucial difference is that we can now create structures that can be folded in, and remain viable in, physiological salt concentrations that are more suitable for biological applications of DNA nanostructures,” explains Dr Högberg. “An advantage of the automated design process is that one can now deal systematically with even quite complex structures. Advanced computing methods are likely to be a key enabler in the scaling of DNA nanotechnology from fundamental studies towards groundbreaking applications,” says Professor Pekka Orponen, who directed the team at the Aalto University Computer Science Department. The possible applications are many. The team at Karolinska Institutet has previously made a DNA nano-caliper used for studying cell signalling. The new technique makes it possible to conduct similar biological experiments in a way that resembles conditions within cells even more closely. DNA nanostructures have also been used to make targeted capsules able to deliver cancer drugs direct to tumour cells, which can reduce the amount of drugs needed. The study was financed by grants from several bodies, including the Swedish Research Council, the Swedish Foundation for Strategic Research and the Knut and Alice Wallenberg Foundation. View our press release More about the study on BBC News Publication ‘DNA rendering of polyhedral meshes at the nanoscale’ Erik Benson, Abdulmelik Mohammed, Johan Gardell, Sergej Masich, Eugen Czeizler, Pekka Orponen & Björn Högberg Nature, online 23 July 2015, doi: 10.1038/nature14586. 

Brain activity can explain the causes of prejudice

Wed, 22/07/2015 - 13:13
An international team of scientists, led from Karolinska Institutet, has investigated the neural basis of racial biases. The results, published in the scientific journal NeuroImage, show that after an aversive experience, differences in brain activity are seen, depending on whether the experience is associated with a member of the person’s own ethnic group or another. People are good at putting people and items into categories. From an evolutionary perspective, it has always been advantageous to be able to quickly determine if something is a danger or an asset. This can however be a problem today since it can lead to unfounded biases. Psychologists use the terms ingroup and outgroup to differentiate between the group you belong to versus all other groups. Scientists have previously shown that we acquire and express fear differently based on the racial identity of a person we learn something about. However, the brain mechanism of these biases has not been studied previously. “Based on what we already know about fear learning, we expected differential brain responses to racial ingroups and outgroups” says Tanaz Molapour, doctoral student at the Department of Clinical Neuroscience, and lead author of the study. “As expected, our results show that there are differences in brain activity after aversive experiences, depending on whether the experience was associated with the ingroup or outgroup.” In the study, 20 white participants were presented with images of two black and two white faces each. One face of each racial group was paired with a mildly unpleasant electrical stimulation, representing an aversive experience. Next, participants watched all the faces again without any shocks being administered, so that the participants learned that the faces were safe. Two days later, the participants took part in a social interactive ball-tossing task, with images of faces of new black and white individuals. Learning responses were measured through physiological arousal, brain responses and behaviour. The researchers found two brain areas in particular, the amygdala and the anterior insula, that played key roles in differentiating between ingroup and outgroup faces. The results show that some of the participants had exaggerated memories of aversive experiences associated with outgroup faces. The brain responses predicted later expressions of discriminatory behaviour towards new outgroup members. According to Associate Professor Andreas Olsson, the principle investigator behind the study, these findings may help us to better understand the brain mechanisms by which small biases based on an aversive experience with a member of another social or ethnic group may turn into a xenophobic response. This study was funded by the Swedish Research Council and the European Research Council. Publication  Neural correlates of biased social fear learning and interaction in an intergroup context Tanaz Molapour, Armita Golkar, Carlos David Navarrete, Jan Haaker, Andreas Olsson NeuroImage, online 10 July 2015  

Active teaching in preparation for a career

Wed, 22/07/2015 - 10:10
Team-based learning (TBL) is a teaching method based on active learning and group work. The primary tool is discussion, which prepares the students for solving problems in their future careers. Teachers Eva Hagel and Mesfin Tessma developed an interest in TBL when they went to extend the course in medical statistics for doctoral students. They wanted to take in more students without compromising on quality. “We’d started to look for alternative teaching methods when it struck me that could shift the focus from passive lecture-based models to more active problem solving,” says Eva Hagel. “The main thing we want the students to get out of this is the ability to solve problems, not to listen to lecturers.” The method was introduced into the Centre for Learning and Knowledge at KI, where the course is held, in the autumn of 2014. On a TBL course, students work in teams of five or six, and the classes are based on problem-assignments that the students prepare at home and then discuss with the aim of reasoning their way to a solution. The group dynamic is quite an important aspect of TBL. The members of a group represent different qualities and backgrounds, and this, hopefully, stimulates cooperation and discussion. The teachers are visible in the classroom but are really meant to let the groups arrive at the answers unaided. “It’s been a challenge for us teachers, since we’re more used to guiding the conversation, asking the questions and often answering them too,” says Ms Hagel. “Now when  get asked something by a group, I try to throw it over to the next group and then we try to reach some kind of consensus together where everyone feels that they’ve been involved in the discussion and produced an answer.” “Many students seem to be more motivated by this active teaching,” says course coordinator Mesfin Tessma. “They get immediate feedback which is very confidence-boosting – and educational. TBL is meant to be fun, and we constantly get something back from the students, which makes us feel energised and motivated too.” I can always get support from the group if there’s something I don’t quite get In the Strix room on the Solna campus, the students sit deep in discussion. They are on the foundation course in medical statistics for doctoral students that is being held along the lines of the team-based learning concept. The course is the first at KI held exclusively as TBL. Similar methods are used at other Swedish universities, but for the students on this course it is a totally new experience. “In Spain, we don’t have TBL as far as I’m aware, but I definitely think that this kind of teaching has its advantages,” says one of the exchange students Sandra Petrus-Reurer. “After all, it’s a very intensive method.” “This is my first TBL course, but I’ve done problem-based learning (PBL) before, which is like TBL,” says David Forsberg, another student on the course. Much thought has clearly gone into how the groups have been divided up, as there is a mix of age, origin and background. Everyone agrees that it is important to have a good group in which everyone is on the same level and no one has to be the one with all the answers or, indeed, all the questions. “We’ve got a group that’s really equal and that often tackles the problem in the same way, and I can always get support from the group if there’s something I don’t quite get,” says Angelina Schwarz, exchange student from Germany. The medical statistics course is only two weeks long and is very intensive. Opinions differ, however, as to whether doctoral students would choose TBL for their other courses. “I prefer to study alone, because I can go at my own pace and don’t have to bother about anyone else, and no one else has to bother about me,” says Angelina Schwarz. “I like the set-up and would definitely choose TBL or PBL over regular teaching,” says David Forsberg. However, everyone agrees that TBL doesn’t suit every aspect of their education. Sandra Petrus-Reurer says that it also depends on how much time you have. “If you go to all the lectures maybe the only time you put into the course is lecture time,” she says. “When you’re studying on a TBL course, quite a lot of your spare time goes into studying, time that you might want to spend doing something else.” Text: Frida Wennerholm Photo: Gunnar Ask    

Turning the spotlight on education

Wed, 22/07/2015 - 10:10
They created headlines last February when their art collection fetched 130 million kronor. Now KI alumni Gunnar Höglund and Anna-Stina Malmborg explain why they are donating some of the money to their KI foundation, and why it’s so important to research into educational methods. Moderna Museet and Karolinska Institutet are to receive a generous donation from the couple after their valuable collection went under the hammer at Sotheby’s in London. For KI’s part, the recipient is the increasingly capital-strong Gunnar Höglund and Anna‑Stina Malmborg foundation, which funds the Karolinska Institutet prize for medical education research. “We’re doing it because we believe that education’s important,” says Dr Höglund. “Our intention is to direct attention onto research in this field.” Art has always been a big interest of theirs, and they have been building their collection since the 1960s. But now that they have served their purpose, the couple want to use the money for something else. That their KI foundation has received an injection of 12 million kronor guarantees that it will continue to be able to award a prize that is large enough to attract international attention. The prize of almost 50,000 euro – almost half a million kronor – goes to researchers who conduct high-quality research in the field of medical education. “Education is fundamental when it comes to everything from basic subject knowledge to skills and attitudes, including how to interact with patients,” says Dr Höglund. “It shapes us – and is researchable too.” Since training to be doctors at Karolinska Institutet, the couple can see that pedagogical development has made great strides forwards. Drs Malmborg and Höglund was part of the ’68-wave, when academics threw all education into dispute, not least students of education such as them. For their entire professional lives, they taught in their respective fields. Anna-Stina worked as a teacher and researcher in bacteriology, and Gunnar worked as a senior lecturer in physiology; he later became a professor at the National Institute for Working Life while variously engaged in pedagogical development at KI. “Education is one of the primary missions of the university, but is often somewhat neglected; research is a bit sexier,” says Dr Höglund. One possible explanation for this is that the people who are made professors are highly qualified in their field of research – but not necessarily in teaching. The fact that research generates new knowledge while education recycles existing knowledge maybe cannot be ignored either, they reason. Moreover, patients and administration must often come first. “We use very few resources to develop education. There is no other area within medicine that is not evidence based.” And this is where the foundation’s prize comes in. It was established in 2001 to reward research that has the potential to deliver long-lasting improvements to the education and training of all healthcare professionals. Seven researchers have won the prize to date for their work on medical education. Ultimately, it’s a matter of producing more skilled practitioners and improving the care they provide. “Not much financial support goes into this, which is why we want to do this,” says Dr Höglund. Text: Madeleine Svärd Huss Photo: Gustav Mårtensson Read more: Karolinska Institutet Prize for Research in Medical Education

Hereditary swellings caused by defective blood protein

Mon, 20/07/2015 - 22:22
Hereditary angioedema type III is a rare, hereditary, and serious disorder, characterised by painful swellings in the skin and other organs. An international team of scientists have published a study in The Journal of Clinical Investigation, where they show that the disease is caused by a defective blood protein, the so-called coagulation factor XII. The results from this study may contribute to future treatment strategies for patients with the disease. Oedema, or tissues becoming swollen due to fluid retention, is a common symptom in a number of pathologies such as allergies or kidney and heart diseases. The swelling is caused by blood vessels leaking fluid into the surrounding tissue. In hereditary angioedema (HAE), the leakage, and hence the swelling, is primarily caused by the hormone bradykinin. HAE is a serious disease with painful episodes of swelling typically involving the skin and gastrointestinal tract. The attacks can be life-threatening since the airways may become obstructed due to the swelling. The most common variants of the disease are called HAE type I and II, and the cause of these are well known. “HAE type III was discovered just recently. If we want to treat the disease, we must first understand the underlying mechanism”, says Dr Jenny Björkqvist at the Department of Molecular Medicine and Surgery, Karolinska Institutet, one of the researchers behind the study. The researchers already knew that patients with HAE type III have a mutation in the blood protein factor XII – but they didn't know why this would cause swellings. In the current study, the researchers discovered that a single sugar was missing in the mutated factor XII in HAE type III patients. The mutated factor XII was found to be overactive. This caused an excess of bradykinin production, resulting in vessel leakage and swelling. There are natural inhibitors in blood that normally prevent factor XII from becoming activated. These inhibitors can also bind to and inhibit the mutated factor XII, but this is not enough to completely stop the overactivation. “We realised that we had to find substances that could block factor XII more effectively. We have previously made an antibody that can inhibit factor XII, and shown that this antibody blocks factor XII driven blood clot formation. In the current study, we demonstrate that the same agent prevents oedema in mice”, says Dr Thomas Renné at the Department of Molecular Medicine and Surgery, Karolinska Institutet, principal investigator of the study. The researchers hope that the study results can be used to establish the first treatment for patients with HAE type III – with the potential for use in a broad array of other types of swelling diseases. Participating in the study were researchers from Karolinska Institutet, Karolinska University Hospital, University Medical Center Hamburg-Eppendorf, University Medical Center Utrecht, Leibniz-Institut für Analytische Wissenschaften, Heidelberg University, University of Bonn, Univerisity Joseph Fourier, CSL Limited and CSL Behring. The research was financed with grants from the Netherlands Organization for Scientific Research (NWO), Ministerium für Innovation, Wissenschaft und Forschung des Landes Nordrhein-Westfalen, Bundesministerium für Bildung und Forschung, the Swedish Heart-Lung Foundation, Stockholm County Council, the Swedish Research Council, the German Research Society and the European Research Council. View our press release Publication  Defective glycosylation of coagulation factor XII underlies hereditary angioedema type III  Jenny Björkqvist, Steven de Maat, Urs Lewandrowski, Antonio Di Gennaro, Chris Oschatz, Kai Schönig, Markus M. Nöthen, Christian Drouet, Hal Braley, Marc W. Nolte, Albert Sickmann, Con Panousis, Coen Maas and Thomas Renné. Journal of Clinical Investigation, online 20 July 2015, doi: 10.1172/JCI77139.

New finding on the formation of fat tissue in man

Thu, 16/07/2015 - 18:18
Bone marrow contains stem cells that normally give rise to new red and white blood cells. A team of researchers from Sweden and France has now shown that bone marrow cells can also form fat. The results are published in the scientific journal Cell Metabolism. While all red and white blood cells derive from stem cells in the bone marrow, the scientific community has been divided over whether bone marrow cells are also able to produce other cell types. In the present study, the researches wanted to ascertain whether cells from the bone marrow could develop into fat cells; the problem is, however, that no experimental method is available for determining the origins of these cells in humans. Using the fact that it is possible to differentiate between grafted and native cells, the researchers conducted their study on 65 adult patients of Karolinska University Hospital who had had transplants up to 31 years ago. “This is an unprecedented follow-up period and one that can therefore give us a great deal more information than the relatively short studies previously done on mice,” says Mikael Rydén, researcher at the Karolinska Institutet’s Department of Medicine in Huddinge. The results of the study, which have just been published in the journal Cell Metabolism, show that during a lifetime some 10 per cent of the graft recipients’ subcutaneous fat consisted of donor-derived cells. And while this was independent of sex and age, the patients’ BMI was an important factor in that overweight patients had up to 2.5 times more bone-marrow-derived fat cells than slim patients. According to the researchers, the results suggest that it is possible for bone marrow cells to develop into different cell types and that certain characteristics of the recipient, such as obesity, can influence this process. “The next step for us is to find out exactly which bone marrow stem cells can become fat cells,” says Professor Rydén. “These studies were done on people who had received a bone marrow transplant to treat leukaemia, and it remains to be seen if the results also apply to people who haven’t had a transplant. If they do, it could lead to new therapies for patients with metabolic diseases, in which adipose cells play a key part.” The study was financed by the Swedish Diabetes Association, the Swedish Cancer Fund, the Swedish Research Council, the Novo Nordisk Foundation, EFSD Lilly European Diabetes Research Programme, CIMED, the European Research Council and the Karolinska Institutet Strategic Research Programme in Diabetes. View our press release Publication: ‘Transplanted Bone Marrow-Derived Cells Contribute to Human Adipogenesis’, Mikael Rydén, Mehmet Uzunel, Joanna L. Hård, Erik Borgström, Jeff E. Mold, Erik Arner, Niklas Mejhert, Daniel P. Andersson, Yvonne Widlund, Moustapha Hassan, Christina V. Jones, Kirsty L. Spalding, Britt-Marie Svahn, Afshin Ahmadian, Jonas Frisén, Samuel Bernard, Jonas Mattsson, Peter Arner, Cell Metabolism, online 16 July 2015. 

Hope for patients with chronic wounds

Tue, 30/06/2015 - 08:08
Most wounds clear up by themselves, but some fail to heal and become chronic. An international team of researchers led from Karolinska Institutet, now unveil the important role of so-called microRNAs in regulating skin wound healing, pointing to new therapeutic possibilities for the treatment of hard-to-heal wounds. Chronic wounds affect 0.2-1% of the population in developed countries and represent an increasing health problem and an economic burden to society. Current treatments focus on optimising controllable factors such as clearing infections. There is a major medical need for treatments that have a direct impact on the wound healing process, and this is why the researchers set out to find therapeutic targets for chronic skin wounds. Wound healing is a complex process that can be divided into several phases – two of these are the inflammatory and the proliferative phase. During the inflammatory phase, damaged and dead cells, bacteria, and debris are cleared out by immune cells. Next is the proliferative phase, where skin cells multiply and there is growth of new tissue. The transition between these two phases is a critical regulatory point that can determine the outcome of the healing process. Hence, the researchers decided to look for factors that mediate this transition. MicroRNAs, or miRNAs, are short pieces of genetic code that, instead of coding for proteins, regulate the expression of genes. Since the discovery of miRNAs in 1993, many studies have shown that miRNAs are involved in a range of diseases. “There is very little known about the expression and function of miRNAs in human skin wounds, but we have previously shown that miRNAs play important roles in the regulation of the cells in the outermost layer of the skin, also called keratinocytes”, says Dr Ning Xu Landén, principal investigator at the Department of Medicine, Solna, Karolinska Institutet. The edge of wounds In a new study, published in the Journal of Clinical Investigation, the researchers collected skin biopsies from the edge of wounds, and looked for changes in miRNA expression during the healing process. They found one miRNA of particular interest, miR-132. Its expression increased during the inflammatory phase and then peaked again in the proliferative phase – just what the researchers were looking for. They found that in the inflammatory phase, miR-132 caused less immune cells to move to the wound, whereas a lack of miR-132 meant more immune cells and hence increased inflammation. During the proliferative phase, miR-132 promoted keratinocyte growth, while a lack of miR-132 decreased cell growth and wounds took longer to heal.  “Our results show that miR-132 is important during the transition from the inflammatory to the proliferative phase and therefore acts as a critical regulator of skin wound healing”, says Dr Xu Landén. “Due to its pro-healing capacity, miR-132 may be an attractive therapeutic target for chronic skin wounds. Our goal is to develop a microRNA-based treatment to promote healing.” First study-author is Dongqing Li, a postdoc at the Department of Medicine, Solna. Except researchers from Karolinska Institutet, researchers from Karolinska University Hospital, and Center for Molecular Medicine in Sweden, The Second Affiliated Hospital of Dalian Medical University, China, and Max Planck Institute for Biophysical Chemistry,Germany, contributed to the study. The research was funded by the Swedish Research Council, LA ROCHE-POSAY Foundation, Hedlunds Foundation, Welander and Finsens Foundation, the Von Kantzow Foundation, the Strategic Research Programme in Diabetes and Karolinska Institutet. View our press release about this study Publication MicroRNA-132 enhances transition from inflammation to proliferation during wound healing Healing Dongqing Li, Aoxue Wang, Xi Liu, Florian Meisgen, Jacob Grünler, Ileana R. Botusan, Sampath Narayanan, Erdem Erikci, Xi Li, Lennart Blomqvist, Lei Du, Andor Pivarcsi, Enikö Sonkoly, Kamal Chowdhury, Sergiu-Bogdan Catrina, Mona Ståhle, Ning Xu Landén J Clin Invest, online first 29 June 2015, doi:10.1172/JCI79052

Information regarding investigation of suspected scientific misconduct

Fri, 26/06/2015 - 11:11
24 June was the deadline for comments on Professor Emeritus Bengt Gerdins report on suspected scientific misconduct. Karolinska Institutet has received 31 replies from the co-authors of the criticized articles. All together the recently submitted material consists of circa 1.000 pages. The final process leading to a decision of the case has now begun, in which  the comments from the co-authors will be taken into consideration. Because of the vast amount of material it is today not possible to set a date for when Karolinska Institutet's decision will be made. Previous articles on the case from the KI intranet Comments on the Research Council’s decision to freeze grant payments to fraud suspect

Being a professor at Karolinska Institutet

Fri, 26/06/2015 - 10:10
The SciLifeLab laboratories on the Solna campus stand adjacent to the offices, and only a few paces separate Anita Aperia’s group’s white lab coats from their desks. Pernilla Lagergren and her group, on the other hand, do all their research on computers and so have no laboratory to go to. Superficially there are many differences between the two professors, but dig a little deeper and you find that their attitudes towards their professional roles are in many respects similar. Anita Aperia has been a professor for 35 years. Pernilla Lagergren took up her post only 3.5 years ago. As professors their job is to pursue research and have overall responsibility for the higher education in which they are engaged. They also appear as experts in a variety of contexts, take part in undergraduate education and sit on committees and boards. On top of all this, they have to lead their research groups and secure funding. “During the active part of my career, I sometimes felt split,” says Professor Aperia. “Now I can devote more of my time to research and supervision, but the split that can appear is dangerous.” “You have to choose and think before you say yes to everything,” says Professor Lagergren. “When you have other duties to perform, it’s your research that has to make way.” Because it was mainly their genuine interest in research that led them to where they are now, as well as the possibility of doing their own research to answer relevant questions and improve things for patients. The title of professor as such has not mattered to them. “When I started to research I had no career plan,” says Prof. Lagergren. “I was propelled into a research career by my passion for making life easier for the patients I care about. It’s the battery powering my research. You need the drive and curiosity.” They agree that patience is an indispensible quality for a professor. Setbacks are common and it is important not to lose heart when things fail to pan out as you had hoped. It is also a challenge, they say, to keep up internationally leading research and, above all, to cope with financial uncertainty. “It’s hard work sustaining a research group,” says Prof. Lagergren. “The grants are often for a couple of years and I have to apply for everything available. It’d be nice to have a certain basic security, maybe a package of resources for those employed as professors.” Prof. Aperia, who has been a researcher for her whole professional life, can compare her role now with what it was before. One difference is that there were fewer professors back in her early years. “The interesting thing is that there was more exchange going on between the faculties,” she says. “The best people in a particular field applied for advertised posts, and I think the mobility and competition was healthy.” Prof. Aperia is currently a full-time senior professor and works with a junior professor, so when she eventually retires from research, the project can continue without her. She sees it as an advantage that those who can attract grants for their research are treated as research leaders even after having reached the formal retirement age. “It’s a creative profession and it’s hard to quit. It’s like being an author or an artist. You don’t have to quit simply because you’ve reached a certain age, but you have to show that you’re doing something useful.”   Name: Anita Aperia. Title: Senior professor at the Department of Women’s and Children’s Health, KI. Time as professor: 35 years. Researches into: How to explain the energy efficiency of the body and its individual cells, with a focus on the salt pump (Na,K-ATPas), the body’s most energy-demanding protein. Name: Pernilla Lagergren. Title: Professor at the Department of Molecular Medicine and Surgery (MMK). Time as professor: 3.5 years Researches into: How recovery after oesophageal cancer surgery can be improved, based on information supplied by the patients.  Text: Karin Söderlund Leifler Photo: Gustav Mårtensson  

Scientific symposium pays tribute to pioneers

Wed, 24/06/2015 - 15:15
Colleagues from around the world came to celebrate the 90th birthdays of cancer researchers Georg and Eva Klein at a symposium that featured lectures by the world’s leading cancer researchers and opened with a special birthday concert. Eva and Georg Klein have been awarded countless prizes and awards over the years for their discoveries in the field of cancer. Although they both turn 90 this year, they are still active tumour biologists at Karolinska Institutet’s Department of Microbiology, Tumour and Cell Biology (MCT). A symposium, arranged by their students and staff, was held on 17-18 June on “The Future of Tumour Biology” at the Nobel Forum, Karolinska Institutet. The programme was kept secret from the couple up to the last minute.   “It was a delightful surprise and such a wonderful programme,” said Georg Klein during the first coffee break of the day. “Everyone is here with new discoveries. It’s so very interesting.”   The symposium was open to an exclusive collection of invited scientists but was streamed live over the internet – with the exception of the lecture by Nobel Laureate Harald zur Hausen as it contained unpublished results.   KI’s vice-chancellor, Professor Anders Hamsten, was noticeably moved when he opened the symposium by thanking the couple for what they have done for KI and for generations of researchers.   “We are here to celebrate science and to pay homage to two fantastic researchers and role models who, together, have made exceptional contributions to Karolinska Institutet and to tumour biology,” he said in his welcoming address.   Professor Hamsten described Georg and Eva Klein as two of KI’s most important researchers of all time. They were pioneers in immunotherapy, which ranks today as one of the most promising breakthroughs for the future of cancer therapy. The speakers at the symposium were the cream of modern cancer research. Apart from scientific lectures, there was also time for personal reflections on the couple’s long career. A closing address was given by Hans Wigzell, professor emeritus of immunology, and one of many to have earned their PhD under the Kleins’ supervision. He gave a vivid description of the Department of Tumour Biology that was originally set up by the couple, and that went on to become a world-leading hub of tumour biology in the 1960s and 70s, attracting scientists from all corners of the world. It also boasted a climate of trust, even for a 19-year old Hans Wigzell, who was taken on as an assistant after only his first year of medical studies.   “It’s Eva’s and George’s incredible ability to teach and inspire, not their scientific results, that is their greatest contribution to the world,” he said. “And for that we thank you, Eva, and we thank you, Georg. Text: Jenny Ryltenius Foto: Gunnar Ask  Videos from the lectures at the symposium will be available soon. Read more about Georg and Eva Klein.

Nobel Prize laureate to seminar on regenerative medicine

Wed, 24/06/2015 - 12:12
Nobel laureate Shinya Yamanaka visits the Karolinska Institute and gives a lecture at a research seminar on regenerative medicine and stem cell research, which takes place June 22 at the Nobel Forum. Shinya Yamanaka at the Center for iPS Cell Research and Application (CiRA), Kyoto University, was awarded the 2012 Nobel Prize in Physiology or Medicine for his discovery that mature, specialised cells can be reprogrammed into immature stem cells, which in turn can develop into any type of cell. At the seminar, Shinya Yamanaka will talk about such induced pluripotent stem cells in the past, present and future. Stem cell research and regenerative medicine are two areas of research that have developed rapidly in recent years and bring high hopes that progress will result in new possibilities to treat a broad range of diseases.

Artifical neuron mimicks function of human cells

Wed, 24/06/2015 - 08:08
    Scientists at Karolinska Institutet have managed to build a fully functional neuron by using organic bioelectronics. This artificial neuron contain no ‘living’ parts, but is capable of mimicking the function of a human nerve cell and communicate in the same way as our own neurons do. Neurons are isolated from each other and communicate with the help of chemical signals, commonly called neurotransmitters or signal substances. Inside a neuron, these chemical signals are converted to an electrical action potential, which travels along the axon of  the neuron until it reaches the end. Here at the synapse, the electrical signal is converted to the release of chemical signals, which via diffusion can relay the signal to the next nerve cell. To date, the primary technique for neuronal stimulation in human cells is based on electrical stimulation. However, scientists at the Swedish Medical Nanoscience Centre (SMNC) at Karolinska Institutet's Department of Neuroscience in collaboration with collegues at Linköping University, have now created an organic bioelectronic device that is capable of receiving chemical signals, which it can then relay to human cells. “Our artificial neuron is made of conductive polymers and it functions like a human neuron”, says lead investigator Agneta Richter-Dahlfors, professor of cellular microbiology. “The sensing component of the artificial neuron senses a change in chemical signals in one dish, and translates this into an electrical signal. This electrical signal is next translated into the release of the neurotransmitter acetylcholine in a second dish, whose effect on living human cells can be monitored.“Agneta Richter Dahlfors Neurologial disorders  The research team hope that their innovation, presented in the journal Biosensors & Bioelectronics,  will improve treatments for neurologial disorders which currently rely on traditional electrical stimulation. The new technique makes it possible to stimulate neurons based on specific chemical signals received from different parts of the body. In the future, this may help physicians to bypass damaged nerve cells and restore neural function. “Next, we would like to miniaturize this device to enable implantation into the human body”, says Agneta Richer-Dahlfors. “We foresee that in the future, by adding the concept of wireless communication, the biosensor could be placed in one part of the body, and trigger release of neurotransmitters at distant locations. Using such auto-regulated sensing and delivery, or possibly a remote control, new and exciting opportunities for future research and treatment of neurological disorders can be envisaged.” This study was made possible by funding from Carl Bennet AB, VINNOVA, Karolinska Institutet, the Swedish Research Council, Swedish Brain Power, Knut and Alice Wallenberg Foundation, the Royal Swedish Academy of Sciences, and Önnesjö Foundation. View our press release about this research Publication An organic electronic biomimetic neuron enables auto-regulated neuromodulation Daniel T. Simon, Karin C. Larsson, David Nilsson, Gustav Burström, Dagmar Galter, Magnus Berggren, Agneta Richter-Dahlfors Biosensors & Bioelectronics, first online 22 April 2015, Volume 71, 15 September 2015, Pages 359–364

Comments on the Research Council’s decision to freeze grant payments to fraud suspect

Mon, 22/06/2015 - 11:11
The Swedish Research Council issued a press release this morning announcing a freeze on grant payouts to ACTREM (the Centre for Regenerative Medicine) at Karolinska Institutet. Karolinska Institutet now has three weeks to formulate an official response to this decision. The ongoing investigation into suspected scientific misconduct at Karolinska Institutet has not yet reached a conclusion. The Higher Education Ordinance charges the vice-chancellor of Karolinska Institutet with investigating such matters, and the current case is to be decided on the basis of complaints levelled against a visiting professor at KI, the expert statement of opinion submitted by the external investigator Bengt Gerdin and the comments expected from the visiting professor and the other authors of the relevant scientific papers. The deadline for these comments is 24 June. The date of Karolinska Institutet’s decision on the matter will therefore depend on the volume of material submitted and the information they contain. The Karolinska Institutet management has no further comment on the Swedish Research Council’s announcement at this juncture. The Swedish Research Council press release (in Swedish) Previous articles on the case from the KI intranet