KI News

Karolinska Institutet’s Pedagogical Prize for 2017 goes to Ewa Ehrenborg, professor of molecular cardiovascular medicine at the Department of Medicine in Solna in recognition of her contributions to interprofessional learning and student-activating research-based education. “Thanks to her pedagogical leadership skills, Ewa Ehrenborg has made a unique contribution to the quality of the clinical placement elements of our programmes,” says prize committee chair and dean of higher education Annika Östman Wernerson. “She is a source of inspiration and an example to both teachers and students.” With her innovative approach to teaching and learning, Professor Ehrenborg has helped to develop a form of student-activating teaching that integrates the latest research and peer learning in novel and imaginative ways. She is also something of a pioneer in developing interprofessional learning between different student groups at all academic levels. “I’m delighted and a little taken aback, as I didn’t even know I’d been nominated this year,” she says. Professor Ehrenborg has been involved in KI’s biomedicine programme for many years as a teacher, course director and member of the programme committee. She is also the director of the Centre for Clinical Education (CKU-KI) and is the coordinator for teaching capacity issues for the Board of Higher Education. “This prize is for all the people around me, both the ones I work with at KI and our partners on the outside, such as from Stockholm County Council and other universities,” she says. “Without them, everything we’ve achieved would not have been possible.” The 2017 Pedagogical Prize will be officially awarded at KI’s installation ceremony, which is to be held in the Erling Persson room, Aula Medica, on 12 October 2017.   Click here for more information about KI’s Pedagogical Prize

Acupuncture has no effect on involuntary childlessness caused by polycystic ovary syndrome (PCOS), the most effective treatment for PCOS being the drug chlomiphene, a joint international study conducted at Heilongjiang University of Chinese Medicine, China, reports. The study, which involved the participation of researchers at Karolinska Institutet, is published in JAMA. Women with polycystic ovary syndrome (PCOS) have high levels of male sex hormone in their blood, causing irregular ovulation and difficulties conceiving. Earlier studies have shown that acupuncture reduces high levels of male sex hormone and produces more regular ovulation. A new study conducted by an international team of researchers has examined whether acupuncture also increases the number of pregnancies and the number of babies born to women with PCOS who are trying to become pregnant. Their aim was to study if acupuncture can be used as an alternative to chlomiphene stimulation, a treatment that while effective also produces adverse reactions. 1,000 women in a clinical trial The study was carried out at Heilongjiang University of Chinese Medicine by researchers from China, the USA, Hong Kong and Sweden in 2012–2015 and involved 27 hospitals. 1,000 women were divided into four groups, two of which received active acupuncture treatment in combination with either chlomiphene stimulation or placebo, the other two receiving a control treatment involving fewer needles inserted superficially without active stimulation, again with either chlomiphene stimulation or placebo. Few negative side-effects The results show that acupuncture is not an effective infertility treatment for women with PCOS who are trying to become pregnant, nor did it have any impact on chlomiphene stimulation. “This is important information, as many women want to use acupuncture to become pregnant,” says Elisabet Stener-Victorin, docent and researcher at Karolinska Institutet’s Department of Physiology and Pharmacology and former visiting professor at Heilongjiang University of Chinese Medicine. “If you have PCOS and want to become pregnant, then drug treatment is the most effective way forward. But for women who don’t wish to become pregnant yet but who have irregular ovulation and other symptoms related to high levels of male sex hormone, acupuncture can be used to relieve the symptoms as the method has no negative side-effects.” Publication ”Effect of Acupuncture and Clomiphene in Chinese Women With Polycystic Ovary Syndrome – A Randomized Clinical Trial” Xiao-Ke Wu, Elisabet Stener-Victorin, Hong-Ying Kuang, Hong-Li Ma, Jing-Shu Gao, Liang-Zhen Xie, Li-Hui Hou, Zhen-Xing Hu, Xiao-Guang Shao, Jun Ge, Jin-Feng Zhang, Hui-Ying Xue, Xiao-Feng Xu, Rui-Ning Liang, Hong-Xia Ma, Hong-Wei Yang, Wei-Li Li, Dong-Mei Huang, Yun Sun, Cui-Fang Hao, Shao-Min Du, Zheng-Wang Yang, Xin Wang, Ying Yan, Xiu-Hua Chen, Ping Fu, Cai-Fei Ding, Ya-Qin Gao, Zhong-Ming Zhou, Chi Chiu Wang, Tai-Xiang Wu, Jian-Ping Liu, Ernest HY Ng, Richard S. Legro, Heping Zhang for PCOSAct Study Group JAMA, online 27 June 2017

The Swedish Foundation for Strategic Research, SSF, has decided to give KI four grants of a total of SEK 138 million in a call within systems biology research. This is a multidisciplinary grant which requires collaboration between biologists, clinicians, mathematicians, computer scientists, engineers, physicists, chemists and others.  Projects are funded with SEK 29-35 million during a five-year period (2017-2021). Researchers/projects at Karolinska Institutet receiving grants Jonas Frisén – Nervcells Development and Networking in the Adult Brain (KI together with KTH and SciLifeLab) Olli Kallioniemi – Precision medicine for optimization of therapies in AML Sten Linnarsson – Cellular reprogramming for stem cell therapy Staffan Strömblad – Microbased system biologic analysis of cell migration (KI together with Uppsala and Lund University) In addition, KI is part of a project concerning new treatment strategies for brain cancer led by Uppsala University.

A high percentage of KIF1Bβ means a greater chance of the tumour spontaneously regressing and disappearing. These are the results of a study by Karolinska Institutet (KI) and the Ludwig Institute for Cancer Research Ltd. The study is to be published in the scientific journal Genes and Development. Neuroblastoma is the third most common form of childhood cancer and causes almost 15 per cent of all cancer-related deaths in children. This high mortality fully reflects both the aggressive nature of the disease and that it often gives rise to secondary tumours (metastases). Paradoxically enough, neuroblastoma also has the highest spontaneous regression frequency of all tumoural diseases. In the present study, the researchers showed that absence of KIF1Bβ contributes to normal neuroblasts not maturing into nerve cells and to a more immature neuroblastoma with a poorer prognosis. “Our study shows that unimpaired maturing of neuroblasts is a basic prerequisite for spontaneous regression of neuroblastoma. What is behind this regression is unknown, but our study is an important piece in the jigsaw for understanding the mechanisms that cause this phenomenon. Understanding this process in greater detail can provide clues for the development of new therapies. For example, it would be interesting to increase levels of KIF1Bβ activity to see if this facilitates, or even induces, tumour regression,” comments Susanne Schlisio, researcher at KI’s Department of Microbiology, Tumor and Cell Biology and at Ludwig Institute for Cancer Research Ltd. High gene expression of the NGF receptor Trka correlates well with good prognoses and with spontaneous regression of the tumour. Conversely, low levels of Trka, partnered with loss of the 1p36 chromosome locus and amplification of the MYCN oncogene, are associated with poor prognoses. “We have previously shown that the kinesin protein KIF1Bβ, which is present on chromosome 1p36, is a candidate tumour suppressor and that a low expression is correlated with lower survival of neuroblastoma patients,” says Schlisio. The research is being financed with funding from the Swedish Childhood Cancer Foundation, the Swedish Cancer Society, the Swedish Research Council, the Paradifference Foundation and the Gösta Fraenckel Foundation for Medical Research. Publications “Neuroblast differentiation during development and in neuroblastoma requires KIF1Bβ mediated transport of TRKA”, Stuart M. Fell, Shuijie M. Li, Karin Wallis, Anna Kock, Olga Surova, Vilma Rraklli, Carolin S. Höfig, Wenyu Li, Jens Mittag, Marie Arsenian Henriksson, Rajappa S. Kenchappa, Johan Holmberg, Per Kogner and Susanne Schlisio, Genes and Development, online 21 June, 2017/297077

The presence of the protein KIF1Bβ can play a central role for the outcome of a neuroblastoma diagnosis. A high percentage of KIF1Bβ means a greater chance of the tumour spontaneously regressing and disappearing. These are the results of a study by Karolinska Institutet (KI) and the Ludwig Institute for Cancer Research Ltd. The study is to be published in the scientific journal Genes and Development. Neuroblastoma is the third most common form of childhood cancer and causes almost 15 per cent of all cancer-related deaths in children. This high mortality fully reflects both the aggressive nature of the disease and that it often gives rise to secondary tumours (metastases). Paradoxically enough, neuroblastoma also has the highest spontaneous regression frequency of all tumoural diseases. In the present study, the researchers showed that absence of KIF1Bβ contributes to normal neuroblasts not maturing into nerve cells and to a more immature neuroblastoma with a poorer prognosis. “Our study shows that unimpaired maturing of neuroblasts is a basic prerequisite for spontaneous regression of neuroblastoma. What is behind this regression is unknown, but our study is an important piece in the jigsaw for understanding the mechanisms that cause this phenomenon. Understanding this process in greater detail can provide clues for the development of new therapies. For example, it would be interesting to increase levels of KIF1Bβ activity to see if this facilitates, or even induces, tumour regression,” comments Susanne Schlisio, researcher at KI’s Department of Microbiology, Tumor and Cell Biology and at Ludwig Institute for Cancer Research Ltd. High gene expression of the NGF receptor Trka correlates well with good prognoses and with spontaneous regression of the tumour. Conversely, low levels of Trka, partnered with loss of the 1p36 chromosome locus and amplification of the MYCN oncogene, are associated with poor prognoses. “We have previously shown that the kinesin protein KIF1Bβ, which is present on chromosome 1p36, is a candidate tumour suppressor and that a low expression is correlated with lower survival of neuroblastoma patients,” says Schlisio. The research is being financed with funding from the Swedish Childhood Cancer Foundation, the Swedish Cancer Society, the Swedish Research Council, the Paradifference Foundation and the Gösta Fraenckel Foundation for Medical Research. Publication “Neuroblast differentiation during development and in neuroblastoma requires KIF1Bβ mediated transport of TRKA”, Stuart M. Fell, Shuijie M. Li, Karin Wallis, Anna Kock, Olga Surova, Vilma Rraklli, Carolin S. Höfig, Wenyu Li, Jens Mittag, Marie Arsenian Henriksson, Rajappa S. Kenchappa, Johan Holmberg, Per Kogner and Susanne Schlisio, Genes and Development, online 21 June, 2017/29707

The Expert Group on Scientific Misconduct at the Central Ethical Review Board of the Swedish Research Council has handed in its review to KI on the case of suspected scientific misconduct regarding the scientifc article "Autologous Peripheral Blood Mononuclear Cells as Treatment in Refractory Acute Respiratory Distress Syndrome", published in Respiration in 2015. The article was referred to the Central Ethical Review Board last autumn by acting Vice-Chancellor Karin Dahlman-Wright as she made the decision to initiate an investigationi on the case. Following the review the case will be further processed before reaching its final decision by KI's Vice-Chancellor, the date for this is not yet set.  

In memory of Professor Lennart Philipson, the board of the Malin and Lennart Philipson Foundation awards a prize and grant for molecular biomedical research with the aim to help young, promising scientists to establish an independent research group after their postdoc training. This year’s awardee is KI researcher Dr Volker M. Lauschke. The grant sum is 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. The prize is awarded in alternate years at Karolinska Institutet and Uppsala University respectively. Volker M. Lauschke, Assistant Professor at the Department of Physiology and Pharmacology, is awarded the the prize 2017 for his work on the development and characterization of physiological hepatic model systems with the goal to study the molecular basis underlying inter-individual differences in drug response. "Volker M. Lauschke has made groundbreaking scientific discoveries and demonstrated independent and outstanding qualities in his line of research," says Professor Li Felländer-Tsai, scientific advisor to the Malin and Lennart Philipson Board. "He indeed deserves this award." “I am deeply grateful to have been granted this award”, comments Dr Lauschke. “During my pre-doctoral studies, I had the pleasure to experience the inclusive, approachable and open-minded spirit that Lennart Philipson managed to evoke at the EMBL in Heidelberg, and which coined so many scientists throughout Europe and worldwide, including myself. I feel honored to receive a prize in Lennart Philipson’s name and will strive to contribute to the dissemination of his scientific leadership philosophy.” This year's prize is to be awarded at Karolinska Institutet's installation ceremony on the 12th of October 2017. Volker M. Lauschke received his Ph.D. from the EMBL and the Combined Faculty of Natural Sciences and Mathematics of the University of Heidelberg in 2013 for his work on tissue patterning using molecular oscillators. In 2014, he moved to Karolinska Institutet as a Marie-Curie fellow to work on the development and characterization of physiological hepatic model systems with the goal to study the molecular basis underlying inter-individual differences in dr ug response. After two years of postdoctoral studies at KI, Dr Lauschke became Assistant Professor at the Department of Physiology and Pharmacology in 2017 in the field of Liver Function and Regeneration.

KI researcher Sten Linnarsson has been elected member of the EMBO. He is one of 65 researchers chosen this year to join this science organisation. In total, EMBO brings together more than 1,700 leading researchers within the life sciences. The main purpose of the organisation is to support talented researchers in their career, increase knowledge exchange and improve the scientific climate in Europe. Sten Linnarsson is a professor and principal investigator at the Department of Medical Biochemistry and Biophysics. He is also affiliated to the national research facility SciLifeLab.  

Researchers at Karolinska Institutet in Sweden have obtained the first 3D snapshots of a sperm protein attached to a complementary egg coat protein at the beginning of fertilisation. The study, which reveals a common egg protein architecture that is involved in the interaction with sperm in both mollusc and mammal, is published in the respected scientific journal Cell. By transmitting the genetic information to the next generation and marking the beginning of a new life, the encounter between female and male gametes at fertilisation is one of the most fundamental processes in biology. Although egg and sperm were first observed centuries ago, how sperm recognises the coat of the egg and penetrates it has remained unknown. Using X-ray crystallographic data collected at the European Synchrotron Radiation Facility (ESRF), Luca Jovine's research team at Karolinska Institutet first visualised the sperm-interacting regions of two egg coat proteins, ZP2 in mammals (including humans) and VERL in the marine mollusc abalone (a classic model system of invertebrate fertilisation). Both of these molecules contain repeated sequences that play a key role in gamete recognition. “Mammals and molluscs are thought to be separated by 600 million years of evolution, and their sperm receptor proteins are almost completely different in sequence. However, comparison of the structures conclusively demonstrates that ZP2 and VERL repeats share a common 3D architecture”, says Luca Jovine, Professor of Structural Biology at the Department of Biosciences and Nutrition and the Center for Innovative Medicine at Karolinska Institutet. Counterpart protein of VERL Subsequently, the research group determined crystal structures of different VERL repeats bound to lysin, the counterpart protein of VERL on abalone sperm. This gave an unprecedented view of how gametes recognise each other in a species-specific way at the beginning of fertilisation. “Abalone was our system of choice for this investigation, as it is one of the few organisms where cognate egg coat and sperm proteins are known. Moreover, different species of abalone spawn in the open sea but, despite overlapping habitats and breeding seasons, hybrids rarely occur”, says Professor Jovine. The VERL-lysin complex structures also suggest how lysin opens a hole into the egg coat, allowing sperm to penetrate into the egg. Lock and key mechanism  “Gamete recognition was first compared to a lock and key mechanism more than one hundred years ago. Our study provides the first example of how this is achieved at the very beginning of fertilisation”, concludes Luca Jovine. Isha Raj and Hamed Sadat Al Hosseini at Karolinska Institutet's Department of Biosciences and Nutrition are co-first authors of the study, which was performed in collaboration with Alessandra Villa at the same department, and Daniele de Sanctis at the European Synchrotron Radiation Facility. It was supported by the European Research Council, the Center for Biosciences, the Center for Innovative Medicine, the Swedish Research Council, the Göran Gustafsson Foundation for Research in Natural Sciences and Medicine, the Sven and Ebba-Christina Hagberg foundation, and an EMBO Young Investigator award to Luca Jovine. Top image: Crystal structure of the complex between a domain repeat of egg coat protein VERL (dark pink) and cognate sperm protein lysin (blue). Artwork by Isha Raj and Luca Jovine. Publication Structural Basis of Egg Coat-Sperm Recognition at Fertilization Isha Raj, Hamed Sadat Al Hosseini, Elisa Dioguardi, Kaoru Nishimura, Ling Han, Alessandra Villa, Daniele de Sanctis and Luca Jovine Cell, online 15 June 2017. DOI: 10.1016/j.cell.2017.05.033

Karolinska Institutet has retained its position in the 51-60 bracket of the Times Higher Education World Reputation Rankings. The list, ranking the world’s most prestigious universities, is based on an invitation-only survey of academics worldwide. “We are of course delighted that Karolinska Institutet has retained its position on the list. This shows that trust in KI’s educational programmes and research remains high. At the same time, the ranking shows only a small part of the university’s continued progress. Naturally, KI has its own processes by which we are able to further develop our quality,” says Karin Dahlman-Wright, acting Vice-Chancellor of Karolinska Institutet. Topping the rankings are Harvard University, MIT and Stanford University. The list was published on 14 June this year. The data used in the Times Higher Education World Reputation Rankings is included as one of several components in a larger survey, the Times Higher Education World University Rankings, which is generally published during the autumn.

The medical programme and eight other programmes at Karolinska Institutet will be affected when fewer patients and patient groups are cared for at the new Karolinska University Hospital Solna. This is what has been revealed in Karolinska Institutet's internal impact assessment analyses. Translational research will also be affected.  The new Karolinska University Hospital Solna, will become a highly-specialized hospital, and large patients groups will be transferred instead to other care- and specialist units. This is just one of the changes in provision of healthcare services being implemented by the Stockholm County Council, SLL.  An internal analysis shows how these changes affect Karolinska Institutet’s education and research. The Board of Higher Education, on behalf of the vice-chancellor, has analysed the consequences for education at KI. One of the most significant consequences is that students who undertake so-called “vocational education” (VFU), or courses at Karolinska University Hospital Solna, no longer will achieve certain learning- and examination goals, if no action is taken. The medical programme is the proframme most affected, when, among other things, the new intensive emergency unit will receive fewer patients and with a limited range of diagnoses. ”Medical students need to encounter patients with common and acute conditions, in order to be able to diagnose independently and treat these patient populations, and there must be arenas for interdisciplinary learning in order for students to be able to develop the ability to work in the multidisciplinary environment. In some cases, all students on a specific course will be affected,” says Annika Östman Wernerson, Dean of Higher Education at Karolinska Institutet. The Board of Higher Education suggests several measures. Among other things, the number of diagnoses performed in the hospital should be increased, and the departments of clinical education, KUA, and clinical education clinics, KUM, should remain at Karolinska University Hospital Solna. The number of places within so-called specialist outpatient care, should also increase through the establishment of new academic specialist centres. In the agreement, where new care providers receive a care assignment, a training and research task must also be clearly included. “We must, naturally, adapt to changes in society, but one must also have real respect for the fact that when we make such extensive changes, it takes time – it’s not like moving chess pieces. In the long run, if you have to move large student groups and educational assignments, you also have to move teaching resources and resources for teachers,” says Annika Östman Wernerson. Clinical research is also affected Annika Östman Wernerson also states that since the teachers also undertake research, this also affects clinical research, and the risk is that the mandatory research link in education will be threatened when students are moved to new care units. “Ultimately, if our students do not receive good or sufficient VFU, then there is a risk that our students will not receive the optimum preconditions for training in different skills and approaches, and that the transition from student to active practitioner will be complicated. Consequently, KI And SLL must be helped to achieve this in a satisfactory manner,” says Annika Östman Wernerson. The Department of Molecular Medicine and Surgery, MMK, is one of the clinical departments at KI that has contributed to the impact assessments. Among other things, MMK runs education at bachelor’s and master’s level for students in medicine and physiotherapy, and has 25 research groups within preclinical and clinical research. “Our research groups generally experience a great deal of uncertainty about what the changed care landscape will actually involve, which activities will be conducted within the new Karolinska University Hospital, and which will be conducted nearby? What will be the dimensions of the emergency ICU, and which potential new care providers will it be important to establish contact with?,” says Anders Franco-Cereceda, Head of Department at MMK. Since emergency care services at the new Karolinska University Hospital constitute a significant research and training basis, the principal investigators at MMK see significant problems in continuing the activities. “There are challenges and we will lose speed and time, but it will also require new ideas and new opportunities which ultimately can lead to improvements. We have to approach our care providers in a spirit of humility and resolve this together,” says Anders Franco-Cereceda. He also states that the key problem is that the physical distance to patients will be greater, which will be difficult during a transitionary period. Mid-June management meeting on next steps “KI’s management has just received the impact assessments and is working on them. It is still too early for us to comment on this,” says Anders Ekbom, acting Pro-Vice-Chancellor at KI. In mid-June, an internal meeting will take place, whereby the management at KI, together with representatives from the Board of Higher Education, the Board of Research and affected heads of department, will discuss the analyses and determine in which way KI will move forward.  Text: Helena Mayer (Not all clinical departments have submitted their reports yet, and these will be published when they are collected.) Programs affected by the operational changes at Karolinska University Hospital Programs that are affected to a greater extent and will not reach the learning and examination goals with the changed operational content – unless special measures are taken Medicine Programmes that are affected to a greater extent and will not reach the learning and examination goals with the changed operational content – unless special measures are taken Audiology Midwifey Biomedicine - Degree and MA Biomedical laboratory science - Focusing on clinical physiology Physiotherapy The Master’s programme in molecular techniques in life sciences Radiography Nursing  Programs where learning and graduate goals can be achieved despite the changing operational content - without taking specific measures Occupational therapy Supplementary education for nurses Speech and language pathology The specialist nursing programme focusing on anaesthetics, intensive care or surgery The specialist nursing programme focusing on children and adolescents The specialist nursing programme focusing on outpatient care, community nursing, psychiatric care and elderly care The specialist nursing programme focusing on medical care, surgical care and oncology, is under review and it is currently difficult to determine the extent to which they will be affected.

Electronic research documentation is to be obligatory at KI; the decision is expected to be taken by June 2017. Introduction has been slowed by criticism of KI’s central e-logbook, KI ELN, but after hands-on support, more people can see the advantages of the system. From January 2019, it is expected to be obligatory for researchers at KI to document their research electronically. Anders Gustafsson, Dean of Research says that the decision is expected to be taken by the summer, after questions from earlier in the year have been discussed by the Board of Research and in the Heads of Department Group. “Electronic management generates better quality research documentation, better organisation, and is more secure. Moreover, it makes it possible to retrieve documentation, which was problematic in a fraud case investigated at KI. It has been voluntary for many years, but not too many active users have come on board. Now it will be made obligatory as part of the preventive measures introduced after the Macchiarini case”, comments Anders Gustafsson. Subject of discussion for a long time Electronic research logbooks have long been a subject of discussion at KI as one way of increasing searchability, transparency and information security in research documentation. Currently, the University’s researchers have the option of using KI ELN, a central system for electronic documentation of their research. However, in the upcoming decision it is electronic research documentation that is obligatory, not use of KI ELN itself. A different system may be used if a Department demonstrates that it satisfies the centrally-set requirements. KI ELN was launched in 2010 and is currently actively used by just about half of KI’s researchers. Cecilia Martinsson Björkdahl, Project Manager at the University Administration with responsibility for research documentation believes that one explanation for this relatively low percentage is that the system has not been obligatory. “It takes time to start using a new system, and the fact that it is not obligatory means it gets prioritised down.” she says. But there has also been pronounced dissatisfaction with the system, which some people consider to be difficult to use and not suitable for their particular type of research. Cecilia Martinsson Björkdahl believes that in many cases this is because the researcher had problems right at the beginning, and these negative experiences persist. “We still hear opinions on KI ELN based on problems that were resolved many years ago. But those groups that get started without too many problems soon quickly recognise the advantages. Such as better searchability, easier collaboration with geographically dispersed groups and a better overview within the researcher group, not least for the group leader”, she comments. Introduction to be decided Precisely how the this obligation will be introduced has not yet been decided. But Cecilia Martinsson Björkdahl comments that the introduction to KI ELN should preferably start with general information meetings by Institute or Department. It should then be followed up with more specific meetings, preferably at the researcher group level, when the introduction can be adjusted to the researchers’ desires and needs. Most problems can be resolved, she believes. “When we sit down and discuss at group level, the problem generally isn’t that big – perhaps it wasn’t as difficult as one believed; perhaps some data doesn’t have to be entered in ELN, but can be stored in a different secure system. Those who do have big problems with the transition to ELN often do not have good routines, anyway. They then not only have to learn a new system but also change their routines, and that is experienced as annoying and limiting,” explains Cecilia Martinsson Björkdahl.   Text: Sara Nilsson

Anna Jervaeus, Adjunct Lecturer at the Department of Neurobiology, Care Sciences and Society, has used KI ELN electronic research documentation since she started as a PhD student at Karolinska Institutet in 2010. A decision is expected soon to make it obligatory for all researchers at KI to document their research electronically. Anna Jervaeus introduced the KI ELN system to her research group in 2010, and today supervises a PhD student who uses it, together with other supervisors. “I think KI ELN is good. I learnt to use the system very quickly, and think it is user-friendly for the functions that I have used. It fulfils its purpose,” says Anna Jervaeus. Among the advantages, she sees the possibility to gather documents together for the research group as a whole, it’s a secure place, and has the option to lock information that has been entered. “Even though I know that I am not going to go in and fabricate something, it is good to know that I always lock the material after a certain time. It also makes it easy to get a good project structure,” she says. KI ELN is often described as produced for lab research rather than the care research that Anna Jervaeus works with. For Anna, that which is called “experiment” in the system can be data collection, manuscript work, planning documents or meeting notes, for example. “I have had to think about what is a reasonable way to divide the work, but have not experienced it as a problem that the system is not adapted to the research we are involved in. I have also had very good help and support from the KI Support Team when I have had questions,” she explains. Making KI ELN obligatory from 2018 Some KI departments will introduce electronic research documentation earlier than 2019. One of them is the Department of Odontology where it has been decided to make KI ELN obligatory from 2018. Head of Department, Mats Trulsson, says they are currently holding introductory courses on how to use the system. “We need to improve our documentation in regard to research, and we see huge advantages with KI ELN. Our entire research will be documented and properly logged, and a leader will be able to retrieve documentation even if a researcher has moved, which at the moment can pose great problems,” he comments. He believes that some researchers can experience the system as more complicated than the method they previously used, but says that this is something we just have to accept if we are to meet the requirement for a functioning research organisation. Obligatory electronic research documentation throughout the whole of KI is, he believes, an excellent idea. “It’s about confidence in research, that you can actually go back and demonstrate with documentation what you have done in research activities,” says Mats Trulsson. High-security documentation Björn Äng, associated with the Department of Neurobiology, Care Sciences and Society, started using KI ELN with a PhD student who was conducting parts of his research within the Armed Forces. High-security documentation was particularly appropriate in that case. That was about six years ago, and he believes that the system has been improved since then. “There have been times when I have been irritated – there have been bugs, and projects that had been entered seized up – but of late everything has functioned well,” he adds. Björn Äng believes KI ELN to be a good secure collection point for documents, such as ethical methods and individual study plans for PhD students. As a supervisor, he also appreciates the formalised communication – when a PhD student has started an experiment, it is sent to him for verification. “It’s good that I have to review it and fill in that I have read and understood it. This makes it more formal and transparent than an ordinary email conversation or paper version. I like that”, he says. However, he does find it slightly inflexible when creating your own structure with sub-categories in the system, and that these structures must be locked. But on the whole, he is positive to making electronic research documentation obligatory. “It is excellent. When you use the electronic logbook, you start to think and find yourself thinking that ‘Hm, yes, I should perhaps document those meeting notes’. It’s a good reminder to have your papers in order”, he comments.   Text: Sara Nilsson

With Karolinska Institutet’s major investments in infrastructure, especially with the new research buildings, the rents are now rapidly increasing. In addition, the laboratory-intensive activities will be required to pay more than others, from 2018, which has given rise to criticism from the academic researchers and scientists. The Biomedicum, Bioclinicum, Neo research buildings, the KM-B animal building, and the renovation of Alfred Nobel’s allé, ANA8, “The Laboratory of the Future,” will all be ready for moving into with the course of a year. “This is an absolutely essential investment,” remarks Stefan Eriksson, Vice-Dean of Infrastructure at the Karolinska Institutet. At the same time, as he admits, a lot is going on simultaneously. Sixty percent of KI’s operations will move into new premises next year, and 80 percent of the laboratory and animal research facilities will be renovated. This costs a lot of money. “When building new buildings, you have to expect that the rents will higher,” comments Stefan Eriksson. The starting point and underlying premise for the new modern research laboratories has been not only that are they required for successful research in the coming decades, but also for synergy benefits as it relates to costly equipment and reduced administrative expenses when several departments move in together. New model for rent levels to be introduced As of 2018, a new model for the setting of rent levels will be introduced with differentiated rents. The laboratory premises will cost more and will have higher rents than offices and educational premises. KI researchers have been criticising the system due to that they believe that the preconditions for experimental research are deteriorating. Among other things, the researchers do not have full access to the information concerning what funds from the external funds may be used to pay the rent. “It is unfortunate that so much has been built at the same time because this will put such a great financial burden on the University. What’s happening now is basically that the bill is being passed on to the researchers. “We should have been a little more cautious,” comments Nils-Göran Larsson, Professor of Mitochondrial Genetics and Head of Department of the Department of Medical Biochemistry and Biophysics (MBB), one of five departments moving into Biomedicum next year. Nils-Göran is also the Chair of Biomedicum’s Heads of Departments group, which rotates its Chair every six months. “When you expand Karolinska Institute’s activities to such an extent, the internal resources available to the individual researcher will be very small and experimental research will become increasingly dependent on external funding,” observes Nils-Göran Larsson. Stefan Eriksson, the Vice-Dean of Infrastructure, who was previously the head of the Department of Physiology and Pharmacology, which is moving to Biomedicum, is well-aware of and deeply involved in the strained rental situation for many research groups. Since the funding from the national government remains at the same level, more external sources of funding is needed. However, while government grants are allocated to departmental salaries and rent, many external funding sources require that the funds granted may not be used for rent. “This means the funds will not be sufficient and it is up to each department to ensure that they have a balance. Then one has to ‘shrink the suit,’ so to say, where tightening the belt can be painful,” comments Stefan Eriksson. Would like to see a helicopter perspectiv Gunilla Karlsson Hedestam, Professor at the Department of Microbiology, Tumor and Cell Biology (MTC), also questions how the research groups will be able to pay the higher rental costs. “What has happened over the past 10 years is that the research funders have come to demand more transparency with more frequent and more detailed financial reports where rental costs are rarely allowed to be included. At the same time, unallocated funds that can be used to pay the rents have become harder to find. It’s an impossible equation for many groups,” observes Gunilla Karlsson Hedestam. Professor Karlsson Hedestam would like to see a helicopter perspective on the part of KI's management in regards to the unsolvable equation concerning rental costs. “I and many others have made attempts to raise these problematic issues at KI for discussion, but one doesn't really want to touch the problem because it’s difficult to find a solution,” remarks Gunilla Karlsson Hedestam. Dean of Research Anders Gustafsson is aware that the investments in new infrastructures have hit some research groups hard. “The Board of Research at KI needs to work together with the departments in order to mitigate the effects, to the extent feasible. Relative to KI’s total income, however, the rent increases are actually not so dramatic,” comments Anders Gustafsson. A working group appointed by the Board of Research is now reviewing the models for the allocation of resources and rent compensation to the departments, which may lead to changes in the future. The working group has discussed the rent compensation for the laboratory-heavy departments on the basis of their rents, but has not yet arrived at any proposal.    Text: Stina Moritz and Madeleine Svärd Huss

From 2018, the rents for laboratory rooms will be higher than for other premises at the Karolinska Institutet. The new rental model has been developed to reflect the actual costs of the new research buildings, and has been decided upon by the University Board of Karolinska Institutet. The total overall costs for Karolinska Institutet’s premises last year amounted to a total of SEK 755 million. In 2018, the figure will exceed one billion kronor, according to Lennart Ilke. As the Facilities Director, he is the head of the Facilities Office at the Karolinska Institutet, which has the responsibility for the provision of the University’s premises and which manages KI’s leasing of premises from outside owners and the internal renting to the University’s departments. The external landlords Akademiska Hus and others send their invoices to the Property Department, which then rents out the premises to the various departments. The departments in turn distribute the cost over their research groups. For many years, the philosophy behind rent-setting has been to equalise the internal rents, meaning that all institutions pay the same amount per square metre irrespective of the actual cost of the premises where the department is located. The exception is animal premises that have higher actual costs and pay a higher internal rent. Since 2014, the internal rent at the Karolinska Institutet has increased from SEK 3,350 to SEK 3,800 per square metre. In 2018, the laboratory-intensive activities will find themselves paying about SEK 4,300 per square metre on average. Proposal from the Board of Resarch A working group at the Board of Research has drawn up the proposal regarding differentiated rent-setting. Their objective was for the rents to reflect the actual costs for each square metre to a greater degree. The higher costs that a laboratory entails, compared to a normal office, justifies a higher rent. Three different factors are used to determine the level of the rent. Factor 1.0 applies to all offices and classroom/educational facilities. Laboratory premises have been assigned a factor of 1.3, which means a 30 percent higher rent, while simple basement premises have a factor of 0.5 and therefore cost one-half the normal rent. “All the new initiatives that we are now implementing, for example at Biomedicum and Neo, specifically concern laboratory-intensive research and that is what is driving the costs up. Therefore, our ambition has been both to protect the educational programme in such a way that it is not negatively impacted from having to bear increased costs due to that the research activities are getting fantastic facilities, and also to protect the research that does not need laboratory facilities,” explains Lennart Ilke. Depending upon the proportions between laboratory spaces and office areas a research group has, the average square metre rental rate between may vary research groups. “However, we will charge Biomedicum collectively, so how the departments choose to allocate the costs within Biomedicine is something that is entirely up to them,” notes Lennart Ilke. Text: Stina Moritz   A look back – from the National Board of Public Buildings to Akademiska Hus Until 1993, it was the state-owned National Board of Public Buildings (Kungl. Byggnadsstyrelsen) that managed buildings and premises for governmental authorities, including Sweden’s universities and other institutions of higher education. The educational institutions paid rent to the authority, but also received state grants to cover their rental costs. In the early 1990s, the National Board of Public Buildings was disbanded and independent state-owned limited companies such as Vasakronan and Akademiska Hus AB took over most of the buildings. “Akademiska Hus was set up at the direct request of the major universities because they needed a property owner with expertise and understanding of the universities’ needs,” notes Lennart Ilke, Facilities Director at Karolinska Institutet. At the same time, the principle for allocating state funding to the universities was revised. The universities were allowed to use their funds for research and education in the manner in which they considered best. This change meant that the universities can rent premises from any property owner they want. However Akademiska Hus came to dominate the scene because to a large extent they took over the universities’ existing premises. *** Karolinska Institutet and other universities receive basic funding from the national government. The University also applies for research funds from various funders of research. The educational programme has a compensation model per student, with different amounts depending on the student’s major. The state funding is allocated from the Board of Karolinska Institutet to the various departments via the Vice-Chancellor and the respective operational board responsible for the activities. Presently Akademiska Hus owns AB 91 percent of Karolinska Institutet’s premises; and in addition, they own the land of Campus Solna. In a few years, the proportions will shift somewhat due to that the property owner Hemsö owns the Neo research building which is under construction in Flemingsberg. Hemsö has also acquired the neighbouring Novum building. About five percent of the Karolinska Institutet’s premises are rented by the National Property Board of Sweden (SFV), Acturum and other smaller real property owners. Sources: Akademiska hus (www.akademiskahus.se) and the National Property Board of Sweden (SFV) (www.sfv.se) along with the Karolinska Institutet.

New research from the Centre for Resuscitation Science at Karolinska Institutet and Stockholm South General (Söder) Hospital in Sweden shows that a specially constructed drone equipped with a defibrillator can be dispatched by alarm and delivered automatically to the site of a cardiac arrest long before an ambulance arrives. The results are published in the respected medical periodical JAMA. “This study clearly shows that unmanned aircraft, drones, show great potential in being able to deliver a defibrillator long before an ambulance arrives, particularly in remote areas,” says Andreas Claesson, paramedic and lead researcher at Karolinska Institutet’s Centre for Resuscitation Science. The specially adapted ambulance-like defibrillator-equipped drone has been developed in partnership with engineers at FlyPulse AB, Trollhättan. For the present study, the drone was dispatched and automatically flown out of view of the pilot within a radius of 10 km. The drone was test-flown to the exact destination to which an ambulance had driven on 18 incidents of cardiac arrest between 2006 and 2013 in the Norrtälje municipality in Sweden; their respective arrival times were then compared. The drone, which was sent from Älmsta (Norrtälje municipality) rescue services, had a response time from alarm to being airborne of only three seconds and an average time from alarm to arrival at the scene of cardiac arrest of approximately five minutes, 16 minutes shorter than was stated in the ambulance records. An important part of the study is that the research team was given permission by the Swedish Transport Agency and the Swedish Civil Aviation Administration to fly out of sight and were therefore able to demonstrate the great potential that drones have to save lives in the event of cardiac arrest. “In areas with longer ambulance response times of up to 30 minutes, the chances of surviving a cardiac arrest are tiny,” explains Mr Claesson. “Drones able to deliver defibrillators can reach the patient inside the first few minutes and are thus a new and important complement to existing emergency services. With an early shock from a defibrillator within the first 3-5 minutes after cardiac arrest, up to 70 per cent of patients can survive the event.” The project was financed with a grant from the Stockholm County Council Innovation Fund. Publication “Time to Delivery of an Automated External Defibrillator Using a Drone for Simulated Out-of-Hospital Cardiac Arrests vs Emergency Medical Services”, Andreas Claesson, Anders Bäckman, Mattias Ringh, Leif Svensson, Per Nordberg, Therese Djärv, Jacob Hollenberg JAMA, 13 juni 2017, 317(22):1-3.

Suicidal behaviour decreases among individuals with bipolar disorder during periods of lithium medication, according to an extensive register-based study conducted at Karolinska Institutet in Sweden. The results are published in The American Journal of Psychiatry. More than one percent of the world’s population is affected by bipolar disorder. The disease is characterised by alternating periods of depression and elevated mood (mania). Medication with lithium and valproate prevents manic phases and has mood-stabilizing effects. It is known that people with bipolar disorder have a high risk of committing suicide, but whether the drugs reduce the risk of suicide has not been sufficiently investigated. Researchers at Karolinska Institutet have, therefore, conducted an extensive register-based study. Many suicides could be avoided ”We now strongly augment the existing evidence that lithium treatment is protective against suicide attempts and suicide”, says Professor Paul Lichtenstein at Karolinska Institutet’s Department of Medical Epidemiology and Biostatistics. ”We estimate that more than ten per cent of attempted or completed suicides could have been avoided if these individuals had been continuously taking lithium during the study period”. The study was performed in collaboration with the University of Gothenburg and included more than 51,000 individuals with bipolar disorder from the Swedish National Patient Registry over an eight-year period (2006-2013). During this period, 10,648 suicide-related events occurred. All participants in the study were compared to themselves during periods with and without medication with lithium and valproate, respectively. The risk of suicide-related events was reduced by 14 per cent while individuals were receiving lithium, as compared with the same individuals while not receiving lithium. Lithium medication has decreased steadily The study also demonstrates that valproate, the most common alternative to lithium, probably has no effect on suicidal behaviour. Lithium medication has decreased steadily in recent years in Sweden. Paul Lichtenstein believes that the results of the study are of relevance for clinical decisions. ”When a doctor is trying to find the best pharmacological treatment for the patient, the anti-suicidal effect of lithium should be taken into consideration, especially for patients with suspected suicidal intentions”, says Paul Lichtenstein. The study was financed with grants from the Swedish Research Council, the Swedish Council for Working Life and Social Research, the Swedish foundation for Strategic Research, and the China Scholarship Council. No commercial interests have been reported. Publication ‘Suicidal Behavior During Lithium and Valproate Medication: A Within-individual Eight Year Prospective Study of 50,000 Patients With Bipolar Disorder’, Jie Song, Arvid Sjölander, Erik Joas, Sarah E. Bergen, Bo Runeson, Henrik Larsson, Mikael Landén, Paul Lichtenstein. The American Journal of Psychiatry, online 9 June 2017.

The risk of relapse among patients with schizophrenia differs depending on what drug is administered, suggests a register study from Karolinska Institutet in Sweden published in JAMA Psychiatry. Clozapine and long-acting injections were linked to fewer re-admissions to hospital than other antipsychotics. Antipsychotic treatment is used to prevent relapse into the mental disorder known as schizophrenia. There are several kinds of antipsychotic drugs today but it has been controversial whether there is any clinically relevant difference between the various treatments when it comes to preventing relapses. About 30,000 patients studied To find out, researchers at Karolinska Institutet carried out a register-based study of 29,823 Swedish patients who were aged between 16 and 64 in 2006 and who were diagnosed with schizophrenia between 2006 and 2013. Every individual was used as his/her own control to eliminate selection bias that might otherwise occur, because patients who are more seriously ill are often treated with other drugs than those who are not as ill. The researchers then looked at what medications the patients had been used and if they had been admitted to hospital again, attempted suicide, stopped taking their medication or died.   “We saw considerable differences between the various antipsychotic treatments. Clozapine and long-acting injections were linked to the best results,” says Jari Tiihonen, specialist doctor and professor at Karolinska Institutet’s Department of Clinical Neuroscience.   20-30 per cent lower risk of re-admission The risk of the patients having been re-admitted to hospital was about 20-30 per cent lower if the patients were given long-acting injections of antipsychotic drugs compared to if the patients received the same medication but orally. This difference was in particular observed in those patients experiencing their first episode.   “Our findings indicate that the risk of the patient being admitted to hospital again varies between different antipsychotics,” says Jari Tiihonen.   The study has been finalised with the help of funds from Janssen-Cilag. Jari Tiihonen has worked as a consultant for Fimea (Finnish Medicines Agency), AstraZeneca, Bristol-Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Janssen-Cilag, Lundbeck and Organon. Publication 'Real-World Effectiveness of Antipsychotic Treatments in a Nationwide Cohort of 29 823 Patients With Schizophrenia' Jari Tiihonen, Ellenor Mittendorfer-Rutz, Maila Majak, Juha Mehtälä, Fabian Hoti, Erik Jedenius, Dana Enkusson, Amy Leval, Jan Sermon, Antti Tanskanen and Heidi Taipale JAMA Psychiatry, online 7 June 2017, doi:10.1001/jamapsychiatry.2017.1322

Scientists at Karolinska Institutet in Sweden report that cancer cells and normal cells use different ‘gene switches’ in order to regulate the expression of genes that control growth. In mice, the removal of a large regulatory region linked to different types of cancer caused a dramatic resistance to tumour formation, but did not affect normal cell growth. The findings, published in the scientific journal eLife, highlight the possibility of developing highly specific cancer drugs with fewer side effects. Humans have close to 20,000 genes to carry out all the functions in a cell. The genes make up only 2 per cent of a cell’s total DNA. What makes us different from one another is mainly the variation in the remaining 98 per cent of our DNA. The variation is believed to alter the activity of regulatory regions or ‘gene switches’ (enhancer elements), which control the activity levels of genes in a cell. It is this variation that is mainly responsible for making individuals more or less susceptible to the development of diseases such as cancer. Gene switch linked to many cancer-related deaths In the current study, using mice, scientists have analysed a large gene switch region that is linked to the risks of developing many different types of cancer, including prostate, breast, colon, bladder and thyroid cancers as well as chronic lymphocytic leukaemia and myeloma. The variation in this region accounts for far more cancer-related deaths than inherited mutations in well-known cancer-causing genes. It is currently unclear why cancer cells use these particular switches, and whether they have any function in normal cells. The scientists turned the gene switches off by removing this region from the mouse genome, and found that its loss has no effect on normal mouse development and growth. Although removing the gene switch region brought down the levels of the nearby cancer gene Myc, the mice remained normal and healthy. However, the mice were strongly resistant to the formation of breast tumours and tumours in the intestine. Can lead to highly specific treatments According to the scientists, these results show that normal cells can function and divide without the genetic elements that are needed for the growth of cancer cells. The study therefore highlights the possibility of developing highly specific cancer drugs. “Since we find that the growth of normal and cancer cells is driven by different gene switches, we can in principle aim at switching off the system for growth only in the cancer cells without any harmful effect on the growth of normal cells. This can lead to the development of highly specific approaches for cancer therapy with much lower toxic side effects”, says Professor Jussi Taipale at Karolinska Institutet’s Department of Medical Biochemistry and Biophysics who led the study. The work was supported by the Center for Innovative Medicine at Karolinska Institutet, the Knut and Alice Wallenberg Foundation and the EU FP7 Health project SYSCOL. Publication “Mice deficient of Myc super-enhancer region reveal differential control mechanism between normal and pathological growth” Kashyap Dave, Inderpreet Sur, Jian Yan, Jilin Zhang, Eevi Kaasinen, Fan Zhong, Leander Blaas, Xiaoze Li, Shabnam Kharazi, Charlotte Gustafsson, Ayla De Paepe, Robert Månsson and Jussi Taipale eLife online 6 June 2017

It has long been assumed that chronic nerve pain is caused by hypersensitivity in the neurons that transmit pain. Researchers at Karolinska Institutet in Sweden now show that another kind of neuron that normally allows us to feel pleasant touch sensation, can switch function and instead signal pain after nerve damage. The results, which are presented in the journal Science, can eventually lead to more effective pain treatments. Severe, treatment-demanding chronic nerve pain is a common condition but the drugs available have, at best, only some efficacy. Since the mechanisms behind nerve pain are largely unknown, the pharmaceutical industry has encountered major setbacks in the development of new drugs. It was previously assumed that certain sensory neurons only transmit pleasant tactile sensations, while other neurons specialise to transmit pain. During chronic nerve pain, normal touch can cause pain, but how this happens has remained a mystery. Scientists at Karolinska Institutet have now discovered that a small RNA molecule (microRNA) in sensory neurons regulates how touch is perceived. Upon nerve damage, levels of this molecule drop in the sensory neurons, which results in raised levels of a specific ion channel that makes the nerve cells sensitive to pain. Could explain different pain thresholds “Our study shows that touch-sensitive nerves switch function and start producing pain, which can explain how hypersensitivity arises,” says Professor Patrik Ernfors at Karolinska Institutet’s Department of Medical Biochemistry and Biophysics. “MicroRNA regulation could also explain why people have such different pain thresholds.” The drug substance gabapentin is often used to treat nerve pain, even though the mechanism of action has not been known. The new study shows that gabapentin operates in the touch-sensitive neurons and blocks the ion channel that increases when microRNA levels decrease. Yet it is still around only half of all patients who respond positively to the treatment. “Nerve pain is a complex condition with several underlying mechanisms,” says Professor Ernfors. “What’s interesting about our study is that we can show that the RNA molecule controls the regulation of 80 per cent of the genes that are known to be involved in nerve pain. My hope, therefore, is that microRNA-based drugs will one day be a possibility.” Research on mice and human tissue The research was primarily conducted on mice but also verified in tests on human tissue, where low microRNA levels could be linked to high levels of the specific ion channel and vice versa, suggesting that the mechanism is the same in humans. “It’s vital that we understand the mechanisms that lead to chronic nerve pain so that we can discover new methods of treatment,” says Professor Ernfors. “The pharmaceutical companies have concentrated heavily on substances that target ion channels and receptors in pain neurons, but our results show that they might have been focusing on the wrong type of neuron.” The study was financed by a USCPRC Award, CERC Program, PAINCAGE, FP7 integrated project, an ERC advanced grant (PainCells), the Swedish Research Council, StratNeuro, the Swedish Brain Foundation, the Knut and Alice Wallenberg Foundation, the Swedish Cancer Society, the Torsten Söderberg Foundation, the Wellcome Trust and Karolinska Institutet. Publication “MiR-183 cluster scales mechanical pain sensitivity by regulating basal and neuropathic pain genes” Changgeng Peng, Lili Li, Ming-Dong Zhang, Carolina Bengtsson Gonzales, Marc Parisien, Inna Belfer, Dmitry Usoskin, Hind Abdo, Alessandro Furlan, Martin Häring, Francois Lallemend, Tibor Harkany, Luda Diatchenko, Tomas Hökfelt, Jens Hjerling-Leffler & Patrik Ernfors Science, online 1 June 2017. Doi: 10.1126/science.aam7671