Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

KI News

Updated: 31 min 48 sec ago

Mapping biological functions of NUDIX enzymes

Thu, 16/11/2017 - 14:42
In a large multidisciplinary project, researchers at Karolinska Institutet have explored different properties of an enzyme family called NUDIX hydrolases. The study, published in Nature Communications, reveals novel insights into their biological functions in human cells. The NUDIX enzymes are involved in several important cellular processes such as cellular metabolism, homeostasis and mRNA processing. Although highly conserved throughout all organisms, their individual structural, biochemical and biological properties remain largely unclear. To address this, Professor Thomas Helleday and Assistant professor Jordi Carreras-Puigvert at Karolinska Institutet’s Department of Medical Biochemistry and Biophysics and Science for Life Laboratory (SciLifeLab) initiated a collaborative study with researchers at Uppsala University, Stockholm University, the University of Ljubljana in Slovenia, and members of the Human Protein Atlas. Comprehensive enzyme profile map The collaboration has resulted in comprehensive data on individual properties and interrelationships of 18 human NUDIX enzymes, revealing four major structural classes. Using a novel algorithm, the researchers integrated all data creating a comprehensive NUDIX enzyme profile map. “This map reveals novel insights into substrate selectivity and biological functions of NUDIX hydrolases and poses a platform for expanding their use as biomarkers and potential novel cancer drug targets”, says Jordi Carreras-Puigvert. The multidisciplinary project included analyses in biochemistry, structural biology, functional genomics, gene expression, protein expression and bioinformatics. It was supported by the European Union–Marie Curie-FP7-People programme, the Torsten and Ragnar Söderberg Foundations and the Knut and Alice Wallenberg Foundation, among others. Publication “A comprehensive structural, biochemical and biological profiling of the human NUDIX hydrolase family” Jordi Carreras-Puigvert, Marinka Zitnik, Ann-Sofie Jemth, Megan Carter, Judith E. Unterlass, Björn Hallström, Olga Loseva, Zhir Karem, José Manuel Calderón-Montaño, Cecilia Lindskog, Per-Henrik Edqvist, Damian J. Matuszewski, Hammou Ait Blal, Ronnie P.A. Berntsson, Maria Häggblad, Ulf Martens, Matthew Studham, Bo Lundgren, Carolina Wählby, Erik L.L. Sonnhammer, Emma Lundberg, Pål Stenmark, Blaz Zupan & Thomas Helleday Nature Communications, online 16 November 2017

"Green Light" introduced to ensure quality in doctoral education

Thu, 16/11/2017 - 10:53
The doctoral supervision training programme introduced at Karolinska Institutet (KI) in 2008 has proved successful. A comparison of exit polls conducted since 2008 shows that doctoral candidates are increasingly satisfied with their education. Now, directors of doctoral studies are to provided with their next quality-assurance tool: At the turn of the year, Green Light will be introduced. “Our work is ongoing and we leave no stone unturned. Exit polls have been of great help,” says Marianne Schultzberg, Dean of Doctoral Education at KI. In June, a longitudinal study was presented comparing exit polls conducted on doctoral students between 2013-2016 with those from 2008-2012. The study clearly shows increased satisfaction among doctoral students. Of those responding between 2013-2016, 93 per cent agreed entirely or in part that overall they had received a good education. This compares with 89 per cent between 2008-2012. Dissatisfaction decreased from 12.8 per cent in the earlier period to 8.6 per cent. The response frequency to exit polls has increased to 83 per cent (from 75 per cent). “It is most gratifying to find that our work is paying off. Both with regard to how doctoral candidates assess their supervisors and the support they receive from study directors, supervisors and others, as well as the quality of doctoral education courses,” says Marianne Schultzberg. At the turn of the year, a new structural initiative will be introduced to ensure the quality of doctoral education throughout KI; Green Light. This means that, prior to recruiting new doctoral candidates, every department must assess whether the preconditions exist for a high quality doctoral education – including sufficient time and expertise for supervision, as well as adequate financing. “Even if in the vast majority of cases these preconditions exist, we believe that the simple fact of raising the issue will have an effect. Departments have had the autumn to prepare their Green Light procedure,” says Marianne Schultzberg. Obligatory supervisor course It is currently obligatory for those researchers wishing to recruit and supervise doctoral students to take either KI’s Introductory Doctoral Supervision Course, introduced in 2008, or an equivalent course. “This has proved to be an excellent initiative. KI’s supervisor course is in great demand and always fully subscribed,” Marianne Schultzberg says. According to Marianne Schultzberg, KI’s researchers demonstrate enormous enthusiasm and commitment when it comes to doctoral supervision. “This represents four years of collaboration. It is a rewarding process to see someone develop,” she says. Doctoral students also confirm that expertise and dedication among supervisors have increased since the introduction of the course. According to the exit-poll study, 80 per cent would recommend their own supervisor to prospective doctoral candidates – an increase from 74 per cent between 2008-2012. The supervision problems demonstrated by the exit polls – the lack of discussion at theoretical level and about the candidate’s postdoctoral future – have also seen improvement since the last measurement. Equal treatment remains a problem Another area that has improved marginally is inequality, discrimination and harassment, although management still feels that there remains much work to do. Last year, 2016, 14.3 per cent of respondents to the survey stated that they had been subjected to such treatment at sometime during their doctoral studies (compared to 16.5 per cent during the period 2008-2012). However, considerably fewer experienced any such behaviour on the part of their own supervisor. “Green Light is a further initiative to come to grips with this,” explains Marianne Schultzberg. Equal treatment is one of the factors that Matti Nikkola, study director at the Department of Cell and Molecular Biology, would also like to see improved going forward. “KI is a university that works to improve health. We must be good at this,” Matti Nikkola says. Just like Marianne Schultzberg, Matti Nikkola considers exit polls to be a great help in this work: “KI has developed an entire toolbox to provide us with excellent support and metrics,” he says. The adoption of a four-year period allows the anonymized breakdown of the information to departmental level, so that study directors can use it to develop their own doctoral courses. Michael Fored, study director at the Department of Medicine, Solna, and a member of the Board of Research Education, sees this as an important activity.  “Educating researchers is an important task for KI. A great deal of KI’s research is carried out by doctoral candidates and sometimes a supervisor may be driven by something other than simply educating their future colleagues. For example, one can’t become a professor without first having doctoral students,” Michael Fored says. He feels that it is important to safeguard the educational component of any doctoral course, rather than viewing it as primarily a staffing issue. “We need to create a common culture and research morality for KI. Doctoral education is a good place to do so.” Text: Ulrika Fjällborg

The Swedish Cancer Society grants KI researchers SEK 180 million

Thu, 16/11/2017 - 10:48
Three researchers at Karolinska Institutet receive the maximum grant as the Swedish Cancer Society distributes 454 million kronor in research funding. In total, 83 researchers at KI receive more than SEK 180 million, of which almost SEK 73 million in new grants. Yihai Cao, professor at the Department of Microbiology, Tumor and Cell Biology, researches in tumours’ blood vessels with the aim of improving the effect of drugs that inhibit the formation of new vessels that tumours need to be able to grow. He is granted 2.25 million kronor a year for three years. Joakim Dillner, professor at the Department of Laboratory Medicine, researches in human papilloma virus, HPV, with the aim of preventing those forms of cancer that are caused by HPV by among other things optimising screening for cervical cancer. He is granted 2.25 million a year for three years.   Jussi Taipale, professor at the Department of Medical Biochemistry and Biophysics, researches in processes that control the growth of cancer cells, knowledge that in the long term might be able to be used to develop new drugs. He is granted 2.25 million a year for three years.

KI placed 15th among the world’s best universities for medicine

Tue, 14/11/2017 - 16:10
Times Higher Education (THE) places Karolinska Institutet at number 15 among the world’s best universities for medicine (pre-clinical, clinical studies and health sciences) in this years ranking. Among European universities, KI finished in 5th place. THE also ranks universities in the field of life science, where KI is in 25th place worldwide and 7th in Europe.   This year, THE presented a new field of psychology and here KI was ranked 19th worldwide and 3rd in Europe. “THE’s new field of psychology shows an exciting result on KI’s part, although this is a relatively small field and a longer series of results is required to better interpret the significance,” says Björn Forslöw, Controller of Operations at Karolinska Institutet.

Apartments for students and researchers are being built

Tue, 14/11/2017 - 08:06
On 7 November, construction began on the new student and researcher accommodation at Campus Solna. The project has been ten years in the planning and is now finally about to be realised. The sun shone as the start of construction on the new accommodation at Campus Solna was celebrated. “This is a vitamin injection; a living and thriving campus needs students and researchers. The housing market in Stockholm is extremely tough and, if we are to attract the best talent, we must be able to offer accommodation.” So says Ole Petter Ottersen, Vice-Chancellor at Karolinska Institutet (KI) who, together with representatives from KI Housing, the Stockholm Federation of Student Unions (SSCO) and Akademiska Hus, presided over the commencement ceremony. The new residential area, which will go under the name KI Residence Solna, is located in the north of Campus Solna on the street Fogdevreten. Occupancy of the 322 apartments, housing 400 students and researchers, is planned to take place between August 2019 and January 2020. Accommodation to be offered to both students and researchers The project comprises three buildings in the form of a letter A, designed to withstand the noise generated by the nearby motorway. The majority of the housing will be studio apartments, although two and four-room apartments will also be built. The homes will be offered to both students and researchers initially in accordance with KI’s prioritisation model and then in queue-order. The hope is that the new accommodation will strengthen Stockholm’s role as a student city. “The lack of available housing in Stockholm is a betrayal of those students who are unable to find accommodation. Today however, we are taking a step towards making this a little easier for them. An investment in student accommodation is the soundest investment Stockholm can make,” says Johan Blixt, chair of SSCO. The close proximity of the new accommodation to the university is an important element of the project. “Studies demonstrate that on-campus accommodation has an large impact on students’ results,” says Kerstin Lindberg Göransson, President of Akademiska Hus. KI is one big construction site The Campus Solna construction project is only one of many ongoing building investments at KI. “Although it may be somewhat frustrating that KI appears to be one big construction site, these new buildings represent our future. This project is only one of many that will make KI preeminent,” says Ole Petter Ottersen. The KI Residence Solna project has a long history. In 2000, temporary apartments were constructed on the site where the new buildings are now being built, with planning of the permanent apartments getting underway in 2007. The problem of noise pollution has been a recurring challenge and building plans have been appealed on several occasions, but now the project is finally being realised. “This is a great day for everyone who has worked so tirelessly on the project. It’s good to see the initiative taken by former director for innovation and infrastructure Rune Fransson ten years ago come to fruition,” says Ole Petter Ottersen. Text: Karin Montgomery KI Residence Solna In total, 322 apartments will be built with room for 400 students and researchers. Occupancy is planned between August 2019 and January 2020. The majority of apartments, 263, will be 23 m2 studio apartments, while the remainder will be two or four-room apartments. The project is a collaboration between Akademiska Hus, KI Housing and KI. KI currently has approximately 400 housing units throughout the Stockholm region. These are managed by KI Housing, a fully-owned subsidiary of Karolinska Holding AB, which is charged with providing accommodation for visiting international researchers and exchange students on behalf of KI.  

Harder for T cells to fight cancer in absence of VEGF-A

Tue, 14/11/2017 - 08:00
Contrary to what was previously believed, the immune system’s cancer-killing T cells are more effective in a tumour’s anoxic environment when they have access to growth factor VEGF-A. In a study from Karolinska Institutet published in Cancer Cell, the researchers show how the T cells not only survive in this oxygen-depleted micro-environment with the help of transcription factor HIF-1a but also become more effective at killing cancer cells inside it. Cytotoxic T cells are important for the immune system in their ability to kill tumour cells. When the T cells enter a tumour, they are thought to exploit transcription factor HIF, which like all transcription factors is a protein that regulates gene expression and thus the function of the cell. Transcription factor HIF is also especially able to help the T cells to adapt to the tumour’s anoxic micro-environment. The researchers now show that it is the variant HIF-1a that enabled the T cells to adapt to this oxygen-depleted environment and thus succeed in killing the tumour. After having analysed the variant HIF-2a they found that it was less important than HIF-1a for the T cells’ ability to adapt to the lack of oxygen and fight the tumour. “We observed that the T cells detect oxygen, and by adapting to a limited amount of oxygen they can enter anoxic tumours, survive within them and then effectively kill them,” says Professor Randall Johnson at Karolinska Institutet’s Department of Cell and Molecular Biology, who led the study. Loss of growth factor resulted in larger tumours The researchers also used mouse models to try to knock out VEGF-A (a growth factor that makes blood vessels grow and one of HIF’s target genes) from their T cells. “Doing this, we found that the tumours grew and that the formation of new blood vessels changed,” explains Professor Johnson. “This is interesting because it was previously thought that tumours starve when you reduce VEGF-A. Our research shows that things are more complex than this. I hope that our discovery will lead to better tumour therapy that maximises the effect of the T cells.” The study was financed by the Wellcome Trust Research Fellowship, the Swedish Cancer Society, the Swedish Childhood Cancer Foundation, the Swedish Research Council, the US National Institutes of Health and the Marie Curie IEF fellowship. Text: Maja Lundbäck Publication “An HIF-1α/VEGF-A Axis in Cytotoxic T Cells Regulates Tumor Progression” Asis Palazon, Petros A. Tyrakis, David Macias, Pedro Velica, Helene Rundqvist, Susan Fitzpatrick, Nikola Vojnovic, Anthony T. Phan, Niklas Loman, Ingrid Hedenfalk, Thomas Hatschek, John Lövrot, Theodoros Foukakis, Amanda W. Goldrath, Jonas Bergh, Randall S. Johnson Cancer Cell, 13 November 2017, doi: 10.1016/j.ccell.2017.10.003

New doctors and jubilee doctors honoured in the Blue Hall

Mon, 13/11/2017 - 14:23
During a festive and solemn ceremony in the City Hall, Karolinska Institutet's new doctors and jubilee doctors were celebrated on 10 November. In his speech, the new vice-chancellor Ole Petter Ottersen, emphasized the importance of knowledge and critical thinking for the university and society as a whole.  

Older people with bowel disease receive older medicines

Mon, 13/11/2017 - 13:09
Inflammatory bowel disease is common amongst older people and there are big differences in the choice of treatment for different age groups. Patients over the age of 60 often receive cortisone drugs instead of more modern medicines that target the immune system. This according to a large registry study from Karolinska Institutet published in Gastroenterology. Inflammatory bowel disease includes Crohn’s disease, which can affect the whole intestine, and ulcerative colitis, which affects the colon and rectum. Symptoms include blood in the stool, diarrhoea and stomach pain. Treatment consists of anti-inflammatory drugs and surgery to remove the damaged part of the intestines. The most common age of onset is 20–30, and previous studies have claimed that it is uncommon for the disease to debut over the age of 60 and when it does, it is less severe. “We therefore sought to ascertain the incidence of inflammatory bowel disease in older age groups and if there is any difference in how they are treated and how they use the healthcare services,” says Åsa Hallqvist Everhov, researcher at Karolinska Institutet’s Department of Clinical Science and Education, Stockholm South General (Söder) Hospital (KI SÖS) and colorectal surgeon at the same hospital. More than one in five were over 60 The study included all new cases of inflammatory bowel disease in Sweden between 2006 and 2014. The resulting group of just under 28,000 patients was split into three sub-groups depending on year of onset: childhood (<18), adult (18-59) and old adult (≥60). Data were sourced from the National Board of Health and Welfare’s patients and prescribed drugs registers, subject to a maximum monitoring period of nine years. The researchers compared the patients’ healthcare consumption with that of a matched group selected from the general population. Just over one fifth of the participants were over 60. The study also shows that this group consumed more healthcare than the two younger groups and more than their matched peers without inflammatory bowel disease. They were also operated on more often and sooner after disease onset, often already within the first year. “It’s common, in other words, for the disease to onset after the age of 60 and we found no evidence that when it does, the disease progress is milder,” says Dr Hallqvist Everhov. Big difference in medication between age groups One important finding was the big difference in medication between the age groups. More younger patients received modern immunomodulating drugs and TNF inhibitors, whereas older cortisone drugs were more commonly given to the older patients. “We don’t know the reason for this, but it could be due either to under-prescription to older sufferers or to prudent choice, since the newer drugs carry certain risks and side-effects,” continues Dr. Hallqvist Everhov. “Older patients often already have other potent drugs.” The researchers plan to examine the causes of the treatment discrepancies in a new study. The study was conducted in association with Söder Hospital. Linköping University, Örebro University, the University of Nottingham, Columbia University College of Physicians and Surgeons and Sachs’ Children and Youth Hospital. The research was supported by the Swedish society of medicine, Mag­–tarmfonden, the Jane and Dan Olsson foundation, the Mjölkdroppen foundation, The Swedish Foundation for Strategic Research, The Swedish Research Council, The Swedish Cancer Society, The Bengt Ihre research fellowship in gastroenterology, The Bengt Ihre foundation, Karolinska Institutet foundations, the regional agreement on medical training and clinical research between Stockholm County Council and Karolinska Institutet (ALF). The study also received an unrestricted grant by Janssen Pharmaceutica NV. The authors declare no conflicts of interest. Publication “Incidence and treatment of patients diagnosed with inflammatory bowel diseases at 60 years or older in Sweden” Åsa Hallqvist Everhov, Jonas Halfvarson, Pär Myrelid, Michael C Sachs, Caroline Nordenvall, Jonas Söderling, Anders Ekbom, Martin Neovius, Jonas F Ludvigsson, Johan Askling, Ola Olén Gastroenterology, online 1 November 2017

Swedish Research Council awards SEK 37 million to KI researchers

Fri, 10/11/2017 - 14:10
The Swedish Research Council has finalised funding for the Natural Sciences and Technology as well as the Humanities and Social Sciences. A total of 13 researchers at Karolinska Institutet will share more than SEK 37 million. The Natural Sciences and Technology grants Kristian Dreij, Department of Environmental Medicine, will receive a total of SEK 3.2 million over four years for the research project Biologiska effekter av felaktig transkription [Biological effects of incorrect transcription]. Victoria Menendez-Benito, Department of Biosciences and Nutrition, will receive a total of SEK 3.2 million over four years for the research project Kartläggning av jästproteomets nedärvning i syfte att utforska mekanismerna bakom åldrande och föryngring [Mapping inheritance of the yeast proteome to study mechanisms underlying aging and rejuvenation]. Rolf Ohlsson, Department of Microbiology, Tumour and Cell Biology, will receive SEK 800,000 in 2018 for the development of methods for analyses of dynamic chromatin structures in single cells. Ute Römling, Department of Microbiology, Tumour and Cell Biology, will receive a total of SEK 3.25 million over four years for the research project Cykliskt di-GMP signalering i Salmonella typhimurium [Cyclic di-GMP signalling in Salmonella typhimurium]. Jesper Tegnér, Department of Medicine, will receive a total of SEK 4.15 million over four years for the research project On the Geometry of Cells – Manifold Learning, Dynamical Systems, and Single Cell Genomics. Roman Zubarev, Department of Medical Biochemistry and Biophysics, will receive a total of SEK 3.454 million over four years for the research project Jonisering, protonisering, radikalisering och icke-ergodisk fragmentering av proteinjoner i gasfas [Ionisation, protonisation, radicalisation and non-ergodic fragmentation of protein ions in gaseous phase]. The humanities and social sciences grants Lisa Berlin Thorell, Department of Clinical Neuroscience, will receive a total of SEK 2.205 million over three years for the research project Relationen mellan emotionsreglering och ADHD i ett longitudinellt perspektiv [Relationship between emotional regulation and ADHD from a longitudinal perspective]. Lars Bäckman, Department of Neurobiology, Care Sciences and Society, will receive a total of SEK 4.6 million over four years for the research project Kognition, hjärna och åldrande: Longitudinella analyser [Cognition, brain and aging: Longitudinal analyses]. Henrik Ehrsson, Department of Neuroscience, will receive SEK 1.05 million in 2018 for the research project Sambandet mellan kroppsupplevelse, visuell varseblivning och minne: experimentella studier och biopsykologiska processer [Relationship between body awareness, visual perception and memory: experimental studies and biopsychological processes]. Armita Golkar, Department of Clinical Neuroscience, will receive a total of SEK 2.046 million over three years for the research project Social reglering av stress och rädsla [Social regulation of stress and fear]. Erika Laukka, Department of Neurobiology, Care Sciences and Society, will receive a total of SEK 2.4 million over three years for the research project Longitudinella luktförändringar i åldrandet. Vad predicerar ett försämrat luktminne? [Longitudinal olfactory changes in aging. What predicts an impaired olfactory memory?] Johan Lundström, Department of Clinical Neuroscience, will receive a total of SEK 4 million over four years for the research project Har luktsinnet en kritisk period? [Does the sense of smell have a critical period?]

Emma Frans nominated for Swedish Grand Prize for Journalism

Fri, 10/11/2017 - 13:41
Emma Frans, researcher at the Department of Medical Epidemiology and Biostatistics, at Karolinska Institutet, has been nominated for the Swedish Grand Prize for Journalism in the Voice of the Year category. The jury explained the nomination as follows: “For addressing the resistance to facts in such an entertaining manner and with scientific precision revealing the Internet's incessant myths.” Emma Frans is a postdoctoral researcher at KI studying psychiatry and pharmaceutical epidemiology. She recently published the book Larmrapporten – att skilja vetenskap från trams [Scare Stories – Separating Science from Nonsense] (Volante). The winners of each category will be revealed at the prize ceremony at Bonniers Konsthall in Stockholm on 23 November.  

Genes influence what we choose to look at

Fri, 10/11/2017 - 08:44
How we explore our world with our eyes can influence everything from social interaction to learning. In a study published in Current Biology researchers at Karolinska Institutet show that our eye movements are partly governed by our genes. What we look at in a situation determines the visual information we access as well as the information we miss. Differences in viewing behaviour can therefore have a significant impact on how we interact socially, how we act in traffic or what we learn from the situations in which we find ourselves.  To discover more about how such differences can arise, researchers at Karolinska Institutet, Indiana University and Uppsala University studied 223 twins between the ages of 10 and 14, half of whom were identical. The researchers showed the participants 80 images of varying content while studying their eye movements in the three seconds for which each image was shown.   “The images had either social or non-social content, as we wanted a representative selection of environments that people encounter in life,” says Terje Falck-Ytter, researcher at Karolinska Institutet’s Center of Neurodevelopmental Disorders (KIND). Identical twins had similar eye movements When the researchers analysed how the participants’ eyes moved over the images, they found that the viewing behaviour of the genetically identical twins was more similar than that of the fraternal twins, in terms of both what part of the picture was viewed and at what point in time.  “For instance, when one twin looked at a certain face for a certain length of time, if the other twin was identical there was a greater probability that he or she would do the same,” says Dr Falck-Ytter. The researchers conclude that genetic factors influence how people use their gaze to receive information. According to Dr Falck-Ytter, people move their eyes several times a second when awake, far too often for it to be due exclusively to conscious decision. “Our results suggest that our genes influence which part of the visual environment is instantaneously selected in every new situation,” adds Dr Falck-Ytter. “These processes are constantly at work and have major consequences for our actions.” Can provide new clues about autism The results can improve understanding of neuropsychiatric disorders like autism, one of the characteristics of which is aberrant viewing behaviour in everyday situations. However, as Dr Falck-Ytter says, they also add to basic knowledge of how our genes affect the way we take in the world around us and how we therefore shape our own living environment. “Children use their viewing behaviour to create their own visual environment, which in turn has a profound impact on their development and the reactions of the people around them,” explains Dr Falck-Ytter. The study was financed by Indiana University, the National Institutes of Health, Stiftelsen Riksbankens Jubileumsfond, the Swedish Research Council, EU, the Strategic Research Area Neuroscience at Karolinska Institutet (StratNeuro), Sällskapet Barnavård, and the Swedish Research Council for Health, Working Life and Welfare. Publication “Genetic Influence on Eye Movements to Complex Scenes at Short Timescales”. Daniel P. Kennedy, Brian M. D’Onofrio, Patrick D. Quinn, Sven Bölte, Paul Lichtenstein, and Terje Falck-Ytter Current Biology, online 9 November 2017 Illustrative examples: Similar gaze of identical twins         The videos show how two identical twins in the study looked at one of the pictures. Each moving dot represents the gaze of one of the twins. The examples show that there was a clear resemblance between the two children in the twin couple, both in terms of where they look and when they move their eyes. The looking patterns of fraternal twins were generally less similar than those of identical twins, but more similar than the gaze of unrelated individuals. This suggests that genetic factors play a role in how children use their eyes when they scan new visual environments. The videos are illustrative examples of cases where the similarity between identical twins was particularly clear, but still reflect the main outcome of the study. (MZ = Monozygotic twins)

Karolinska Institutet comments on the UKÄ decision on the Macchiarini case

Thu, 09/11/2017 - 17:12
Comment: The Swedish Higher Education Authority (UKÄ) has today levelled serious criticism at Karolinska Institutet in a supervisory decision delivered to the Board of Karolinska Institutet, regarding issues relating to Paolo Macchiarini’s activities at KI during the period 2013-2016. UKÄ has reviewed a number of issues that fall within the Authority’s remit. In its decision, UKÄ confirms that KI has failed to fully investigate Macchiarini’s secondary activities, failed to investigate a number of suspicions regarding misconduct in his research, been deficient in those investigations into research misconduct that have actually been instigated into Macchiarini, and extended one of his appointments in contravention of Karolinska Institutet’s appointments procedure. As a result of these failures, during 2018 UKÄ will monitor KI’s work on the action plan, review governance documents and cases in selected areas and conduct specific sampling. Overall, UKÄ presents criticisms raised in the external investigation commissioned by the Board of Karolinska Institutet in February 2016, following the massive criticism directed at KI in connection with SVT’s television documentary Experimenten (the Experiment). This external investigation, led by Sten Heckscher, presented its findings in September 2016. The recommendations contained in Heckscher’s report, as well as the internal audit conducted at CLINTEC, form the basis for the action plan presented by the then vice-chancellor in October 2016. Mikael Odenberg, chair of the Board of Karolinska Institutet, today commented on UKÄ’s decision: “Karolinska Institutet and the Swedish Higher Education Authority are in full accord with regard to KI’s management of a number of issues related to Paolo Macchiarini’s activities. It is apparent that control was lost in the pursuit of scientific excellence and that serious mistakes and errors were made at KI. Under the leadership of KI’s vice-chancellor, comprehensive efforts are now underway to implement the action plan based on the recommendations made by Sten Heckscher at the behest of the Board. This work is intended to quickly rectify the obvious flaws in, among other things, internal regulations and their application and working practices,” says Mikael Odenberg, who continues: “I welcome the fact that during 2018, UKÄ intends to monitor this work and the implementation of the action plan. We see this as welcome support for our continued efforts. However, the action plan is only a small part of the necessary measures. In the long term, it is a matter of changing our culture and attitudes, of raising ethical issues to a higher level in both education and research, and of ensuring good regulatory compliance and a greater ethical awareness throughout the organisation. The fact that the judiciary did not consider it possible to bring Macchiarini to account further underlines the responsibility that rests with academia to keep its own house in order.” Ole Petter Ottersen, vice-chancellor of Karolinska Institutet, also welcomes UKÄ’s decision: “This decision will be followed up and will complement all of the other work we are doing to ensure regulatory compliance and ethical awareness within the organisation. UKÄ’s scrutiny will also be linked to our new Strategy 2030, work on which is already underway. Now is the time to look to the future. KI must emerge stronger from this crisis,” says Ole Petter Ottersen.

Breast cancer recurrence risk lingers longer than expected

Thu, 09/11/2017 - 06:00
Even 20 years after a diagnosis, women with oestrogen receptor-positive breast cancer still face a substantial risk of cancer returning or spreading, according to a new analysis from an international team of investigators published in The New England Journal of Medicine. The results could influence decisions about long-term endocrine therapy. Standard treatment for oestrogen receptor-positive, or ER-positive, breast cancer includes five years of the endocrine-based treatments tamoxifen or aromatase inhibitors. Researchers from the Early Breast Cancer Trialists’ Collaborative Group, EBCTCG, including researchers from Karolinska Institutet, analysed data from 88 clinical trials involving almost 63,000 women with ER-positive breast cancer. The patients all received endocrine therapy for five years and were free of cancer when they stopped therapy. Over the next 15 years, a steady number of these women saw their cancer spread throughout the body, as late as 20 years after the initial diagnosis. The risk of recurrence was directly tied to the original tumour’s size and characteristics, and to the number of lymph nodes that were cancerous. Women with large tumours and four or more involved axillary nodes had a 40 per cent risk of a distant cancer recurrence by year 20. Women with small, low grade cancers and no spread to the nodes had a 10 per cent risk of distant spread during the same period. Long-term endocrine therapy could be more effective Recent studies have suggested that 10 years of endocrine therapy is even more effective than five years, sparking the question of whether every woman should continue on this therapy for 10 years. Life-threatening side effects are rare with these therapies, but they might impact patients’ quality of life by mimicking menopausal symptoms. Aromatase inhibitors can cause osteoporosis, joint pain or carpal tunnel syndrome. “Our results show that ER-positive breast cancer should result in a discussion between the physician and the patient where they together weigh the benefit against the risks of continuing the anti-oestrogen therapy beyond five years”, says Jonas Bergh, Professor at Karolinska Institutet’s Department of Oncology-Pathology, senior physician at Radiumhemmet and co-chairman of EBCTCG. To assess 20-year risks, the researchers had to study women who received their breast cancer diagnosis many years ago. Treatments have improved since then, so recurrence rates are expected to be somewhat lower for women who were diagnosed more recently. The research was financed by Cancer Research UK, the British Heart Foundation, the University of Oxford and the Medical Research Council, UK, among others. This news article is based on a press release from the University of Michigan. Publication “20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years” Hongchao Pan, Richard Gray, Jeremy Braybrooke, Christina Davies, Carolyn Taylor, Paul McGale, Richard Peto, Kathleen I. Pritchard, Jonas Bergh, Mitch Dowsett & Daniel F. Hayes. The New England Journal of Medicine, online 9 November 2017

Vague leadership and organisation in focus in this year’s employee survey

Wed, 08/11/2017 - 14:05
Vague leadership and poor knowledge of goals and strategies and a deteriorated work environment are some of the results from this year’s employee survey. In spite of this, many employees would recommend Karolinska Institutet (KI) as an employer and the majority are happy with their workplace. Many of KI’s employees feel that the organisation is indistinct; only 55 per cent of the almost 4,300 who answered the questionnaire in 2017 say that it is clear who is responsible for what. And only 63 per cent say that they are familiar with and understand KI’s overarching goals and strategies. “These are a few of the most alarming areas that were identified through this year’s survey. The organisation is indistinct and employees do not know what KI’s goals and strategies are,” says HR manager Mats Engelbrektson. The labour organisation Saco-S, with about 2,500 members at KI, has just received the results and will now study them in more detail. Saco-S chair Torkel Falkenberg emphasises the importance of a clear organisation. “Lack of clarity at management level creates a lack of clarity that permeates the entire organisation,” he says. Torkel Falkenberg can nonetheless see positive trends for the future. “Today we have a vice-chancellor who talks about sustainability goals and says that what we work with from day to day at KI also should benefit the whole world. That goal is not just about excellence, and it creates the feeling of being part of a global movement for a better world. And he also recalls that the sustainability goals include a sustainable working life. An organisation that is durable and takes advantage of employee skills - also over time,” Torkel Falkenberg says. Vice-Chancellor Ole Petter Ottersen says that the employee survey constitutes a good foundation for strategic work. “The results illustrate the importance of beginning work on a new strategy and overhauling our organisation. A clear strategy and fit-for-purpose organisation are necessary to create the best possible conditions for research and education at Karolinska Institutet,” he says. Less chance to recuperate Another area showing worse results this year is the work climate. Workload, balance and recuperation show a negative trend. Research assistants, researchers, senior lecturers and lecturers feel they have the worst balance. 38 per cent of all those who responded say that their sleep has been disturbed once or more a month due to thinking about their work. “We see a trend towards a deterioration of the balance between work and leisure and the chance to recuperate. It is important that we support our managers in their responsibility to prioritise tasks together with their staff and take action early when we see signs of too high workloads and too little opportunity to recuperate," says Mats Engelbrektson. Now the HR-department is going to study the results in more detail before deciding what more needs to be done. The employee satisfaction index stabile The employee satisfaction index is relatively unchanged (71 on a scale from 1 to 100) compared to the previous survey, which was conducted in 2014 (72). The index is a measure of commitment distributed over work climate, organisation, leadership and goals and strategies. There are also positive outcomes in this year’s survey. One is the high eNPS figures, that is to say how many employees would recommend their workplace to a friend or acquaintance, which are higher this year. “I am happy to see that what KI has gone through over the past three years has not affected us as negatively as one might think. We do not know why, but I choose to interpret it as a sign of optimism and faith in the future at KI. How strongly people recommend us, however, varies widely between departments,” Mats Engelbrektson goes on. Zero-tolerance policy on discrimination 200 people (5 per cent) said that they have been subjected to discrimination, which is below the result (7) of other universities according to Quicksearch, the company that conducted the survey. This is an increase from 2014, but the comparison is not entirely accurate because the questions in the latest surveys are not identical. “The mere fact that it occurs at all is an indication that something is amiss. Saco-S thinks KI should work proactively with the issue,” says Torkel Falkenberg. “Any value above zero is unacceptable because KI has a zero-tolerance policy on discrimination. We will always continue to work to prevent and handle discrimination, victimisation, bullying and harassment. It is, however, very gratifying to see equal treatment in third place on the list of positive outcomes,” says Mats Engelbrektson. The survey covers KI employees with a position that represents minimum 40 per cent of a full-time position and who have employed for at least six months, a restriction that has come in for some criticism. “We chose to draw the line there to secure the response frequency but for the next survey we’re considering a sub-group for people with a lower full-time equivalency,” Mats Engelbrektson says. Text: Karin Montgomery About the employee survey The survey, which is anonymous, was conducted during September and October this year. The survey covered people with a position that represents minimum 40 per cent of a full-time position and who have employed for at least six months. A total of 5,392 questionnaires were sent out and 4,297 people completed the survey, a response rate of 80 per cent (75 per cent in 2014). The results will be posted at the departments from 31 October until 24 November. Action plans are to have been drawn up by January 31 next year.

Low school grades linked to attempted suicide into middle age

Wed, 08/11/2017 - 08:00
Young people with lower school grades than their peers run a higher risk of mental ill-health and attempted suicide. In a new study published in the journal Acta Psychiatrica Scandinavica, researchers from Karolinska Institutet show that this risk persists into middle age. The study examined the records of over 26,000 women and men from their final year of compulsory education at the age of 16 to a maximum age of 46, cross-referencing their school grades with data on post-attempted suicide hospital treatment. “We found that the lower the school-leaving grade, the higher the risk of attempted suicide,” says Dr Alma Sörberg Wallin, postdoc researcher at Karolinska Institutet’s Department of Public Health Science. “The risk was five times higher for pupils with the lowest grades than for those with the highest.” The correlation was equally strong for women as for men, and the results were unaffected by childhood socioeconomic position, parental mental illness and suicidal behaviour, or immigrant background. Unclear what lies behind the correlation It is still unclear what lies behind the relationship between low school grades and mental ill-health and attempted suicide. One hypothesis is that lower cognitive ability could be an underlying cause since previous research has shown this to be linked with school performance and suicidal behaviour. The researchers therefore added a year-six IQ test (age 12) to the statistical control, but found no support for this hypothesis. On the contrary, they found that a higher IQ correlated with a slightly higher risk of attempted suicide in women, taking into account the relationship between cognitive ability and grade. “Our research has shown that school grades are an important risk marker for future attempted suicide events,” says Dr Sörberg Wallin. “This is useful information for school personnel and others who work with preventing mental ill-health in school pupils and the general population.” A public health problem School is a place well suited for preventive intervention, and grades could form the basis of such efforts, say the researchers. “Suicidal behaviour is a public health problem that we need to know more about if we’re to take effective action on it,” adds Dr Sörberg Wallin. The leader of the research project, Dr Daniel Falkstedt at the same department, also stresses that they do not yet know why lower grades are linked to increased risk of attempted suicide. Is it because lower grades lead to lower academic achievements and restricted opportunities in life, or are low grades primarily an indication of other underlying personal issues, such as impulsiveness, conduct disorder or psychological distress? This is a question for future studies to answer. The study was financed by Forte (the Swedish Research Council for Health, Working Life and Welfare). The authors declare no potential conflicts of interest. Text: Maria Ekström Publication “Suicide attempt predicted by academic performance and childhood IQ: a cohort study of 26 000 children” Sörberg Wallin A, Zeebari Z, Lager A, Gunnell D, Allebeck P, Falkstedt D. Acta Psychiatrica Scandinavica, online 8 November 2017, doi: 10.1111/acps.12817

Medical nutrition-drink may affect development of early Alzheimer's

Tue, 07/11/2017 - 13:53
In a new study, an international research team shows that a medical nutrition-drink, consisting of, among other things, essential fatty acids and vitamins, may have an impact on disease development in patients with so-called prodromal Alzheimer's disease. This nutritional treatment did not improve the patients’ memory, but seems to slow down neurodegeneration and help patients cope somewhat better with everyday tasks. The study is a part of the EU FP7 funded research-project LipiDiDiet and was recently published in the journal Lancet Neurology. "Although the primary objective of the study, to see an effect on the neuropsychological test battery, was not met, the results on secondary effects are extremely valuable. This means that we are learning more about how nutritional treatment can affect prodromal Alzheimer’s, which is a pre-dementia stage of the disease," comments Professor Miia Kivipelto at Karolinska Institutet’s Department of Neurobiology, Care Sciences and Society, who led the Swedish part of the current study. Read more about this research Publikation 24-month intervention with a specific multinutrient in people with prodromal Alzheimer's disease (LipiDiDiet): a randomised, double-blind, controlled trial Soininen H, Solomon A, Jelle Visser P, Hendrix SB, Blennow K, Kivipelto M, Hartmann T on behalf of the LipiDiDiet clinical study group. Lancet Neurology, online 30 October 2017

Fertility preservation with hormone stimulation did not increase risk of breast cancer relapse

Mon, 06/11/2017 - 14:24
Women who received hormone stimulation for fertility preservation did not have a higher relapse rate in breast cancer compared with unexposed control women in a study from Karolinska Institutet published in Breast Cancer Research and Treatment. The results could influence the clinical practice for young cancer patients wishing to pursue fertility preservation. Women presenting with breast cancer are often excluded from programmes for fertility preservation due to a fear that the hormonal stimulation treatments required to retrieve eggs/embryos for cryopreservation might increase the risk of relapse. Because breast cancer is the most common malignancy in women, researchers at Karolinska Institutet conducted a study to investigate the safety of fertility preservation in 188 women with breast cancer who had undergone hormonal treatment from 1999–2013 in the Stockholm healthcare region. The control group of 378 women comprised data retrieved from the Regional Breast Cancer Register. Data linkage to the register allowed the researchers to follow-up the progress of both the exposed women, who underwent fertility preservation treatment, and the unexposed matched controls, who did not receive fertility preservation treatment, over the same period. A primary quality of survival issue The study findings reveal that women who received hormone stimulation did not present with a higher relapse rate than unexposed control women. The results remained virtually unchanged after adjustment for age and calendar period of diagnosis, tumour size, oestrogen receptor status, affected lymph nodes and chemotherapy treatment. “Our work could potentially influence medical care and clinical practice to the benefit of young cancer patients wishing to pursue fertility preservation options”, says the responsible researcher, Kenny Rodriguez-Wallberg, at the Department of Oncology-Pathology, Karolinska Institutet. “Having a chance to build a future family after surviving cancer is currently recognized as a primary quality of survival issue for young people with cancer”. The work was supported by grants from The Swedish Research Council, the Swedish Society for Medical Research, the Swedish Society of Medicine, the Swedish Cancer Society, Radiumhemmet’s research grants, Stockholm County Council (ALF) and the Karolinska Institutet. Dr Rodriguez-Wallberg is supported by a Clinical Investigator Grant from Stockholm County Council. Publication “Safety of fertility preservation in breast cancer patients in a register-based matched cohort study” Rodriguez-Wallberg KA, Eloranta S, Krawiec K, Lissmats A, Bergh J, Liljegren A. Breast Cancer Research and Treatment, online 2 November 2017

KI wins the big pot in Swedish Research Council Medicine and Health grants

Mon, 06/11/2017 - 12:24
With success in 116 of 204 grants awarded, Karolinska Institutet will receive a total of almost SEK 490 million. The Swedish Research Council approves approximately SEK 1 billion in grants within Medicine and Health. The four researchers from Karolinska Institutet who have been awarded the highest grants within Medicine and Health 2017 will each receive SEK 9 million divided over five years. Abdel El Manira, Department of Neuroscience, receives a grant for his research on the organisation of the neuronal networks that control motor movements. Johan Ericson, Department of Cell and Molecular Biology, receives a grant for his research on identifying a clock mechanism that controls the production of motor neurons and serotonergic nerves from natural stem cells. Tomas Olsson, Department of Clinical Neuroscience, receives a grant for his research on genetics and pathogens in neuroinflammation, focusing on multiple sclerosis. Thomas Renné, Department of Molecular Medicine and Surgery, receives a grant for his research on the interaction of coagulation, inflammation and congenital immunodeficiency. Proof of Concept in life sciences The Swedish Research Council has also reached a decision on grants for Proof of Concept in life sciences. The purpose of these grants is to bridge the gap between basic research and the commercialisation of research results. Two researchers from Karolinska Institutet will each receive SEK 1.2 million. Ulf Eriksson, Department of Medical Biochemistry and Biophysics, receives a grant for developing new pharmaceutical candidates for stroke, fibrosis and cancer. Agneta Richter Dahlfors, Department of Neuroscience, receives a grant for developing optotracers for studies of bacterial biofilm within an infected host organism.

Troponin linked to increased risk of death

Thu, 02/11/2017 - 15:24
A blood test that measures the presence of heart specific proteins called troponins is used by A&E hospitals to diagnose myocardial infarction in patients with chest pain. But even normal levels of the protein in patients without infarction increase the risk of death, a study from Karolinska Institutet published in the renowned Journal of the American College of Cardiology shows. Patients with measurable troponin levels should therefore be investigated, suggest the researchers. Troponins leak into the blood and become measurable in blood samples taken from patients with acute conditions, such as myocardial infarction or pulmonary embolism. However, even chronic leakage can give rise to measurable levels, such as in the elderly or in the event of chronic kidney disease and severe heart failure. “We know that a large group of patients have chronically higher levels than 14 ng/l, which is the normal upper limit,” says study leader Martin Holzmann, docent at Karolinska Institutet’s Department of Medicine, Solna and physician at Karolinska University Hospital. “This group is larger than the number of heart attack patients, but so far such findings have not led to any action being taken since we don’t know enough about the risks that elevated levels entail.” Chronically elevated troponin levels To ascertain how chronically elevated troponin levels affect the risk of death and heart disease, the researchers reviewed the medical records of all patients over 25 years of age who sought medical attention at the emergency clinic at Karolinska University Hospital in Huddinge or Solna with chest pain for the first time between the years 2011 and 2014. At least two registered troponin measurements were required during the three-year follow-up period for them to qualify for the study. Patients with severe kidney disease, acute myocardial infarction or other acute conditions were excluded, leaving just over 19,000 patients. Complementary data were then sourced from the National Board of Health and Welfare’s patient, prescribed drug and cause of death registers. The researchers found that just under ten per cent of the patients had above normal troponin levels, and that half of them had no previously diagnosed heart condition. A third had a troponin level of 5–14 ng/l, which is seen as normal but which proved to be strongly linked to death. In the 5–9 ng/l range, the risk of death was double that of the control group, which had immeasurable troponin levels. In the10–14 ng/l range, the risk was three times as high. Of those who had a troponin level above 50 ng/l, one third died within the first year of follow-up. Measurable troponin levels were also associated with a high risk of myocardial infarction and an even higher risk of heart failure. Good risk marker for heart disease “As we can see, troponin is a good risk marker for heart disease and death,” says Dr Holzmann. “Patients with measurable troponin levels should therefore be examined. It may be suitable for these patients to be referred by their general practitioner for echocardiography, which can reveal heart disease. And the troponin test can be used to identify which patients need to be treated for hypertension, for example, or high cholesterol. We have to get better at evaluating patient risk, especially in primary care.” The study was conducted in association with Danderyd Hospital and Sahlgrenska University Hospital and was financed by Stockholm County Council. Martin Holzmann has received consultancy fees from drug companies Actelion and Pfizer. Text: Inna Sevelius Publication “Stable high-sensitivity cardiac troponin T levels and outcomes in patients with chest pain” Andreas Roos, Nadia Bandstein, Magnus Lundbäck, Ola Hammarsten, Rickard Ljung, Martin J. Holzmann Journal of the American College of Cardiology (JACC), online 23 October 2017

Science becomes art

Thu, 02/11/2017 - 09:51
On the 31 October the exhibition The Invisible Body opened at Sven-Harry’s Art Museum in Stockholm. A number of researchers at KI are represented by pictures from their own research. The new art exhibition The Invisible Body (Den osynliga kroppen) narrates the story of ongoing medical research from the perspective of medical images. “In my role as a communicator, I have often experienced the difficulty in finding a way to talk about research in a comprehensible manner yet without oversimplification. The idea for this exhibition came when a researcher showed me a beautiful image obtained during her work. We soon realised that, through her picture, we had discovered an excellent way of discussing her research. Here, beautiful images become an entirely new point of entry to science,” explained Mona Norman, project manager at the Ragnar Söderberg Foundation, at the exhibitions opening. The image was taken in Maria Kasper’s research group at KI’s Department of Biosciences and Nutrition and shows an area of the skin that is particularly susceptible to cancer. Her laboratory studies follicular stem cells in order to understand their link to wound healing and cancer. “The opportunity to gain access to an advanced microscope that makes it possible to take these types of pictures and to among other things study the development of individual cancer cells, was the reason why I chose to locate my research at KI,” says Maria Kasper who attended the vernissage together with doctoral candidate Karl Annusver, the photographer behind the image.   The exhibition collects a number of works that depict subjects invisible to the naked eye, giving us new insights into how the healthy and diseased body functions. However, these images are also things of beauty. They are artworks that, after the exhibition closes, will be auctioned to raise funds to support research. And, according to Saida Hadjab at KI’s Department of Neuroscience, there are similarities between art and science. “Creativity is a vital ingredient in the work of both artists and researchers.” Saida herself has two pictures in the exhibition and is one of the project’s two scientific coordinators. Her own great interest in photography has proved an important motivational factor behind her research work at the microscope. “I search for images that are both elucidatory and beautiful. A beautiful picture has a greater ability to convey its message,” she says. The exhibition runs until 7 January 2018 and is an initiative from Ragnar Söderberg Foundation in collaboration with Sven-Harry’s Art Museum. It includes pictures from Hagströmer Medico-Historical Library, Lennart Nilsson Photography and researchers at a number of universities. In conjunction with the exhibition, a number of popular science lectures will be held. Learn more about the exhibition here.  In conjunction with the exhibition, a number of popular science lectures will be held. Learn more about the exhibition. The full list of researchers from Karolinska Institutet that contributed to the exhibition: Eduardo Guimaraes // Christian Göritz lab John Schell // Fredrik Lanner lab Carmelo Bellardita // Ole Kiehn lab Tomas McKenna // Maria Eriksson lab Elisa Floriddia // Fanie Barnabé-Heider lab Javier Calvo Garrido // Anna Wredenberg lab Anders Hånell // Histology course, Neuroscience department Cajsa Classon // Liv Eidsmo lab Saida Hadjab // François Lallemend lab Karl Annusver // Maria Kasper lab Jan Krivanek // Igor Adameyko lab Shigeaki Kanatani & Laura Heikkinen // Per Uhlén lab Katarzyna Malenczyk // Tibor Harkany lab Sten Linnarsson // Sten Linnarsson Lab Matthijs C. Dorst // Gilad Silberberg lab Ada Delaney // Camilla Svensson lab Margherita Zamboni // Jonas Frisén lab Laura Comley // Eva Hedlund lab Nicola Crosetto // Nicola Crosetto lab Sebastian Hildebrand // Fredrik Lanner lab Daniel Fürth // Konstantinos Meletis lab Sofie Ährlund-Richter // Marie Carlén lab Tomas McKenna // Maria Eriksson lab Benjamin Götte // Gerald McInerney lab Anna Rising Lab

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