KI News

Researchers at Karolinska Institutet and the universities in Lund and Cambridge have found that fragments from the human Brichos protein have the ability to prevent neuronal and brain damage caused by amyloid-beta in Alzheimer’s disease. The findings are being published in the journal Nature Structural and Molecular Biology. Studies on brain tissue from mice show that the Alzheimer’s disease-peptide amyloid-beta (A-beta) degrades oscillations of the neuronal network in the gamma-frequency band (30-80 Hz), which are important for memory and learning. However, in the current study researchers show that in the presence of Brichos this degradation was completely prevented. The team also studied A-beta in test tubes with and without Brichos, and found that the preventive effects are associated with a highly specific function of this protein. Brichos was found to bind to aggregated forms of A-beta, thereby blocking the surfaces that would otherwise be responsible for generation of neurotoxic activity and cell death. The contributing scientists from Karolinska Institutet were Jenny Presto, Firoz Roshan Kurudenkandy, Henrik Biverstål, Lisa Dolfe, Janne Johansson, and André Fisahn. The study was funded by, amongst other organizations, the chiff Foundation, the Swedish Research Council, the Crafoord Foundation, the Swedish Alzheimer Foundation, the Frances and Augustus Newman Foundation the European Research Council, the Strategic Program in Neurosciences at the Karolinska Institute, the Swiss National Science Foundation, and the Wellcome Trust. Publikation The molecular chaperone Brichos breaks the catalytic cycle that generates toxic Aβ oligomers Samuel I. A. Cohen, Paolo Arosio, Jenny Presto, Firoz Roshan Kurudenkandy, Henrik Biverstål, Lisa Dolfe, Christopher Dunning, Xiaoting Yang, Birgitta Frohm, Michele Vendruscolo, Jan Johansson, Christopher M. Dobson, André Fisahn, Tuomas P. J. Knowles, and Sara Linse Nature Structural & Molecular Biology, advance online publication 16 February 2015, doi: 10.1038/nsmb.2971

Last Friday the King of Sweden visited Karolinska Institutet in Solna. On Monday 16 February, Queen Silvia came to visit the department of neurobiology, care sciences and society (NVS) at Karolinska Institutet in Huddinge. The queen was welcomed by the board member and head of the department of neurobiology, care sciences and society professor Maria Eriksdotter, in conjunction with a meeting of the board of the Silviahemmet Foundation. She also met representatives from the department in the research areas focused on ageing and dementia disorders. All of the NVS courses and study programmes were presented at the meeting, including the new online master's course in dementia care for physicians that KI offers in collaboration with the Silviahemmet Foundation. The title of “Silvia Doctor” is offered upon completion of the course, as are the titles “Silvia Nurse” or “Silvia Nursing Assistant” after similar study programmes for nurses and nursing assistants. During the queen's visit there was also a presentation of the ongoing production of the online master's course for occupational therapists and physiotherapists focusing on dementia care, which is conducted in collaboration with the Silviahemmet Foundation. The queen also visited a class where she met physiotherapy students and she concluded her visit with a lunch at the NVS. Text: Pia Hellsing Photo: Ulf Sirborn  

When new buildings were erected on KI’s Solna campus in the early 1990s, a laboratory, a street and an auditorium were named after Anders Retzius and his son Gustaf Retzius. A debate is now raging over whether these names should be kept or changed. Both father and son were famous anatomists in the 19th century scientific community and are two of the leading figures in the university’s history. As part of their anatomical research, they collected crania from around the world in the interests of racial science. Many of these countries have now asked to have the skulls returned and KI has been criticised for not handling the matter promptly enough. Last spring, a doctoral student at the Department of Neuroscience raised the issue of Retzius’s problematic links to eugenics in a letter to the vice-chancellor, and suggested that the name be removed from the various places around KI that honour it. Olof Ljungström at the medical history and cultural heritage unit prepared the background material for the university’s reply. We can’t acquit 19th century anatomists of racial science, we can’t whitewash them and simply erase it from the history books. “History needs to be written differently to how it was before,” he says. “The proposer asks, in a way, the right questions. Enough information is available on Retzius for him to start asking questions. If Retzius’s name disappears, people won’t be able to ask such questions any more in this way.” The issue is not a new one, and Olof Ljungström thinks that it will probably return even if the name is removed. “We can’t acquit 19th century anatomists of racial science, we can’t whitewash them and simply erase it from the history books. On the other hand, if we only base our decision on what to do in this situation on what’s problematic, it won’t be the perfect way out either. A working synthesis must include both aspects.” No decision on the name has yet been taken. “We’re planning an open seminar on the question, after which we’ll be considering the naming issue,” says University Director Per Bengtsson. “We must take into account the associations a name has, even if this is by no means the complete picture of who Retzius was.” A decision was taken last autumn on several activities for discussing the history of eugenics and racial science at Karolinska Institutet, including an internal seminar at the neuroscience department this spring. “We’re also planning an international symposium, possibly in 2016, on human museum specimens and how they relate to racial science,” says Eva Åhrén at the medical history and cultural heritage unit.   Text: Karin Söderlund Leifler Photo: Gunnar Ask

On Friday 13 February, the King of Sweden visited Karolinska Institutet. The aim was to learn more about the university’s innovation system, select research areas and the new internet-based global MOOC:s that was launched at KI in 2014. The King was greeted by Vice-Chancellor Anders Hamsten at the entrance to the Aula Medica building and introduced to researchers and teachers who gave a presentation of a few important areas of research. Among other subjects, KI’s innovation system – which offers expert skills within entrepreneurship and business development was discussed. The system is to ensure that innovations and ideas within the field of biomedicine are available and at the disposal of the health services. The King also got to see how large-scale methods have revolutionised research and diagnostics on certain hereditary diseases. He was also given a presentation on the field of regenerative medicine, and of MOOC:s, Massive Open Online Courses. This autumn, KI was the first university in Sweden to offer these open, free-of-charge online courses, and thus earned a position as an important actor on the global education arena.

Scientists at Karolinska Institutet have evaluated a new Alzheimer’s therapy in which the patients receive an implant that stimulates the growth of a certain type of nerve cell. The results, which are published in the journal Alzheimer's & Dementia, suggest that the introduction of a nerve growth factor can prevent neuronal degradation in Alzheimer’s patients. Patients with Alzheimer’s disease suffer a selective and early breakdown of so-called cholinergic nerve cells, which require a specific nerve growth factor (NGF) – essentially a group of proteins necessary for cell growth and survival – to function. As NGF levels decline, the cholinergic nerve cells begin to degrade and the patient’s condition slowly deteriorates. In an attempt to curb the breakdown of the cholinergic nerve cells, researchers at Karolinska Institutet’s Centre for Alzheimer’s Research and their colleagues at Karolinska University Hospital’s neurosurgery clinic and the Danish biotech company NsGene introduced NGF directly into the brains of Alzheimer’s patients. To do this, they used NGF-producing cell capsules, placing them in the basal fore-brain where the cholinergic cells reside using precision stereotactic surgery. There the capsules, which can easily be removed, release NGF to the surrounding cells in order to prevent their degradation. Presence of specific markers  The study now published in Alzheimer’s & Dementia is based on data from six Alzheimer’s patients. To gauge whether the NGF release had any effect on the cholinergic nerve cells, the researchers assayed the presence of specific markers of functioning cholinergic cells. This cell system communicates using acetylcholine, which in turn produces an enzyme called ChAT (pronounced Cat) that is found both inside and outside the cells. The team therefore developed a method enabling them to measure ChAT in the cerebral spinal fluid for the first time. “Our results show that when the patients received NGF, there was a significant increase in ChAT in the CSF,” says Dr Taher Darreh-Shori, one of the researchers involved in the study. “The patients that exhibited this increase were also those that responded best to the treatment. Our PET scans also showed an increase in cholinergic cell activity and metabolism in the brain.” Retardation of memory impairment In addition, the researchers were able to detect a retardation of memory impairment over time compared with untreated patients. While all this suggests that cholinergic functionality improved in the Alzheimer’s patients who had received NGF therapy, the team adds the caveat that far-reaching conclusions should not be drawn from the results: “The results are promising, but must be treated with circumspection as only a few patients participated in the study,” says principal investigator Professor Maria Eriksdotter. “So our findings will have to be substantiated in a larger controlled study using more patients.” The NGF-producing cell capsule method (Encapsulated cell biodelivery) was developed by NsGene. The paper’s first authors are doctoral students Azadeh Karami and Helga Eyjolfsdottir. The study was financed by grants from several sources, including the Foundation Olle Engkvist Byggmästare, Åke Wiberg’s Foundation, Åhlén Foundation, the Dementia Fund, the Odd Fellows, the King Gustaf V and Queen Victoria Free Mason Foundation, Karolinska Institutet’s strategic research programme in neuroscience (StratNeuro), the Swedish Research Council and Swedish Brain Power (for a full list of financiers see the published article). View our press release about this study Publication Changes in CSF cholinergic biomarkers in response to cell therapy with NGF in patients with Alzheimer’s disease Karami, A., H. Eyjólfsdóttir, S. Vijayaraghavan, G. Lind, P. Almqvist, A. Kadir, B. Linderoth, N. Andreasen, K. Blennow, A. Wall, E. Westman, D. Ferreira, M. Kristoffersen-Wiberg, L. O. Wahlund, Seiger, Å. , A. Nordberg, L. Wahlberg, T. Darreh-Shori, M. Eriksdotter Alzheimer’s & Dementia, uncorrected proof online 9 February 2015, doi 10.1016/j.jalz.2014.11.008

The international FANTOM5 consortium, including scientists from Karolinska Institutet, has made major strides toward resolving common mechanisms in cell differentiation. In a new study published in the journal Science, they describe more than 400 stages of cell maturation in 33 different cell types in mouse and human. The FANTOM5 is led from the research institute RIKEN in Japan, and gathers scientists from 114 institutions around the world. In this large-scale project, scientists have created an atlas that shows which different genes that are used in virtually all cell types that humans are composed of. The atlas was launched in March 2014, and attracted attention worldwide. In the current study, the team has made an effort to map the transcriptional changes that occur when cells differentiate from one cell type to another cell type, both during cell development and in response to stresses or infection. Researchers investigated differentiation time series in 19 human and 14 mouse cell types, in total more than 400 stages of cell maturation. The technology used made it possible to see exactly where the genes are ‘read’ from the DNA, and to find the regulatory switches called ‘enhancers’ that are responsible for activating the reading of genes in the appropriate cells at the correct time point. Shared patterns The team found that just after the cells start to differentiate or react to stimuli, there are shared patterns in gene and enhancer activity between all the studied cells types. Enhancers are activated in the first 15 minutes after stimuli. At 30 to 100 minutes, the enhancers activate a specific type of regulatory genes (transcription factors), which in turn have the ability of activated other genes and over time forming a cascade of changes. These patterns were shared across all the studied cells, but the individual genes and enhancer that made up the patterns were specific to each cell type. This indicates that the team has found underlying rules for how cells differentiate that applies to all mammals, knowledge which may be an important part of the puzzle in understanding how the human body works in health and disease. The FANTOM5 consortium is led by Professor Yoshihide Hayashizaki at RIKEN, and  includes over 500 scientists from more than 20 countries over the whole world. The researchers from Karolinska Institutet who are members of the consortium are Andreas Lennartsson, Michelle Rönnerblad and Carsten Daub at the Department of Biosciences and Nutrition, and Peter Arner, Anna Ehrlund and Niklas Mejhert at the Department of Medicine, Huddinge. FANTOM5 was made possible through a grant from the Japanese Ministry of Education, Culture, Sports, Science and Technology, while the EU and a number of other research funders have also contributed. View a press release from RIKEN about this research Publication Transcribed enhancers lead waves of coordinated transcription in transitioning mammalian cells Erik Arner, Carsten Daub, Kristoffer Vitting-Seerup, Robin Andersson et al, Berit Lilje, Finn Drablos, Andreas Lennartsson, Michelle Rönnerblad et al. Science, online 12 February 2015, doi: 10.1126/science.1259418 List of all FANTOM publications

The one has been vice-chancellor of KI for two years, the other CEO of Karolinska University Hospital for just four months. Here in an interview they talk about the challenges they share and about integrating research and education with academic healthcare and innovation. What are the main challenges facing the partnership between KI and the university hospital? Anders Hamsten: In general, it’s about how we’re to integrate the university and the university hospital more effectively. This is our main challenge, and one that can be broken down into different parts. One important part is the issue of leadership. In both organisations we talk a great deal about the importance of good leadership, academic leadership for knowledge-intensive, complex organisations. It’s also important to nurture a common leadership that works in both environments. Another part of the challenge is organisational: to harmonise our respective structures so that they dovetail better. And then, of course, we have the issues of financing all our joint activities, and to work together to improve the quality of academic healthcare. Another part of the challenge is organisational: to harmonise our respective structures so that they dovetail better. Melvin Samsom: I’d prefer to start at the other end: what are the options and possibilities available to us? KI and the university hospital together are uniquely endowed: such a renowned university next to such a large university hospital on two campuses. If we can coordinate our strategies, we will be in a strong position to drive the development of future healthcare systems, amongst other things. We both agree that our partnership is not operating at its optimum, and there is much to be gained by improving it. Resources will always be in short supply, but there is a lot we can improve using what we currently have at our disposal. One example is to take the areas in which KI excels and make them areas in which the university hospital also excels, so that we can benefit more from each other. Another important issue is the brand. To much of the world, both our organisations are “Karolinska”. It’s a powerful brand that we should take great of. In which areas should the two organisations integrate more? Anders Hamsten: In all core operations. As I see it, there are four areas: research, education, academic healthcare and, as the fourth point, innovation, implementation and knowledge dissemination. But to achieve this, we need to work with a fifth area: a common infrastructure. This is now being built up at both KI and the university hospital, and it’s something of a challenge to make sure that it’s designed in a way that favours our collaboration. What else does the infrastructure include? Melvin Samsom: It’s easy to think of material investments, but most of all I want to emphasise the importance of soft infrastructure: the people. The new environments being built are, of course, important, and we have a desperate need for new IT systems, but it’s still more important to find the right people – people who are in sync with us and how we’re changing. This has been one of the pivotal questions of our conversations: how can we get the right people in the right place? The ones who can tackle the four areas that Anders mentioned: academic healthcare, research, education and innovation. I know that this hasn’t always been the case at the hospital and that healthcare has been our main focus. This, however, will change over the coming years. What will happen to your education programmes? Anders Hamsten: One interesting question is to identify the most suitable clinical learning environments for our students: how relevant they are to our different programmes, what highly specialised care is done there, what the mix of the major disease categories looks like, what supervisory resources are available, and so on. Since the patient flow changes quite quickly, this will be a challenge. Melvin Samsom: We need to look at it from the students’ vantage point. The educational world is changing rapidly, and it’s now possible to study at universities in different countries by distance. Young people don’t want an education that assumes they’ll stay working in the same field until they retire. Do we offer the flexibility they’re looking for? Another question is: do we have the right patient groups at the university hospital for their education? What other caregivers need to be engaged to give the students proper clinical experience? Is it harder now to combine healthcare production with education and research? Melvin Samsom: I’d say it is. It’s more expensive to treat patients at a university hospital than in other places, and since we’re publicly financed, we need to justify why this is the case and why a patient has to be treated at this higher cost instead of somewhere else. Sometimes it’s because we’re the only ones with the competence. It can also be because the treatment of that patient group is closely linked to education or research. Uncertainty about the magnitude of this extra cost and what we get for it easily causes problems when healthcare is to be combined with education and research. Anders Hamsten: And to that I’d like to add the question of leadership. Not only the leadership of our respective organisations, whereby we both want to reinforce the academic leadership, but also political leadership, which must help to ensure that the university hospital receives the resources it needs. Without them, both healthcare and the education of the next generation of medical staff will suffer. Our political leaders must be explicit in making it clear that the university hospital plays a special role amongst all the hospitals and specialist clinics in the Stockholm region. KI and the university hospital must remain mutually critical, in a constructive sense. Melvin Samsom: Patient flows are changing, and the university hospital will be changing its patient mix. We will be focusing on more complex, academic healthcare that we have had, the kind of healthcare that demands close collaboration with research and education. We need to look critically at which patients require treatment at the university hospital and which can be treated more cheaply elsewhere. Because of this we have to cooperate in a more organised way with a network of other caregivers operating around us. You seem to agree on most things. Is there anything you don’t see eye to eye on? Melvin Samsom: It’s true that we’ve found much common ground. The fact that we have similar backgrounds – we’re both clinicians, researchers and managers – has no doubt helped to make it easy for us to agree. I think we have very similar ideas about our common goal. But of course then, when the job has to get done, lots of questions will crop up along the way that we’ll have different opinions about. Which is good. KI and the university hospital must remain mutually critical, in a constructive sense. It’s through such criticism that academic environments advance. Text: Anders Nilsson Photo: Gustav Mårtensson

Once every year a selection of the best articles are translated into English and collected in an English issue of Medicinsk Vetenskap. Order your issue of Medical Science 2015 and read articles about cooling treatments, obesity, cardiac care and many other things.  Browse the 2015 issue of Medical Science Order the 2015 issue of Medical Science The magazine Medical Science       A cool treatment saves the brain Are you a shiverer? Then you cope better with the cold. But without protective mechanisms, the body’s core temperature quickly drops and there is a risk of frostbite. At the same time, a body that is cooled down copes better without oxygen, something researchers can utilise to save lives.

The duties and roles one has to combine at work tend to increase over the years, as does the scope of one’s spheres of responsibility. Often it’s wonderful, but sometimes it gets too much. As atherosclerosis researcher Gabrielle Paulsson-Berne knows. Like most of her senior colleagues, she has several hats to juggle in her work at KI. It’s great being a multitasker. And frustrating. And essential. Fifteen years ago, Dr Paulsson-Berne was the one most au fait with her research group’s lab at the CMM (Centre for Molecular Medicine); today, as senior research associate, she rarely even finds time to take part in the experiments. These days she is a researcher, a supervisor, a deputy group leader, a course coordinator, a teacher and a member of various committees and networks at KI. Amongst other things. She usually has to delegate her lab work to postdocs and doctoral students. “Although last Monday I made time for it. It’s a special feeling to meet three or four people early in the morning and then to spend all day in the lab. It’s nice to see how just how much my fingers remember!” Researches the affects of atherosclerosis Dr Paulsson-Berne researches into how the immune system affects atherosclerosis, and has teamed up with vascular surgeons at the university hospital to create BIKE, a biobank containing surgically removed plaque (accumulations of matter that constrict the arteries) from patients with atherosclerosis. “From each of the samples we’ve gathered data on 20,000 genes, on whether they’re turned on or off. We’re now following up the leads we’ve found there in the search for mechanisms involved in the process of plaque spread.” Started the biomedicine Master's programme In 2007 she was in charge of setting up the “Frontiers in translational medicine” course on the newly started biomedicine Master’s programme, and she has been course coordinator ever since. The course is held every autumn semester, and her intention was to spend more time in the spring on her research. But things haven’t quite turned out that way. “Putting together a major course is a complex thing. Arranging such a large schedule, recruiting teachers, updating the course contents, pedagogical development…all this has to take place between courses.” All the general work she has to do with her research team also competes with her own research. This includes arranging its seminar series, organising the internal structures it needs to operate, being the senior backbone, the glue, that holds the team together over time while junior researchers do their time and then move on, etc. Dr Paulsson-Berne has been with the group since it started; she was recruited as a postdoc in the mid-1990s. Likes doing different things “The difficult thing is having time for everything. But I like doing many different things, and it seems as if all of us seniors at KI are multitaskers. There are many of us who just can’t help taking on new tasks – it’s fun and rewarding to have a finger in many pies. You learn so much, gain a huge contact network, and meet people from all over the world. I’d say that many of us would find it boring to do the same thing all the time. “But then the university is dependent on us multitaskers. We’re the ones who get insight into what’s going on elsewhere in the organisation, who discover points of convergence, and make different areas of the university cross-fertilise each other. Being a multitasker is also a way of surviving in the university environment. Sticking to just one thing makes you very vulnerable.” She goes on: “But it’s easy to take on too many duties. Because they’re fun and important, because I appreciate being asked, and because, like many of my colleagues, I’m an inveterate time optimist. I’m also a team person, you see. There’s no way I could sit on my own. KI is a wonderful crucible of enthusiastic nerds from all over the world. There’s something seductive in that.” Text: Anders Nilsson Photo: Gunnar Ask

Involuntary dyskinetic movements induced by treatment with levodopa (L-dopa) are a common problem for people with Parkinson’s disease. Now, however, researchers at Karolinska Institutet and Lund Universityseem to be close to a novel therapy to this distressing side effect. A treatment study published in the journal Brain shows that a drug that stimulates certain serotonin receptors in the brain counteracts the dyskinesia causing effects of L-dopa. The substance tested by the team, eltoprazine, is a so-called serotonin receptor agonist that targets receptor types 5-HT1A and 5-HT1B. Serotonin is a neurotransmitter involved in the regulation of many biological phenomena, such as satiation, sleep and mental wellbeing, as well as movement. Earlier research on animal models for Parkinson’s conducted by Anders Björklund, professor of histology at Lund University, and Per Svenningsson, professor of neurology at Karolinska Institutet, showed promising results using serotonin receptor agonists against L-dopa-induced hyperkinesia, and have prompted the researchers to examine if the principle also operates in humans. “Eltoprazine has been tested on patients in the psychiatric field, but this is the first time a study has been done with Parkinson’s disease,” says professor Svenningsson, who led the clinical study with Håkan Widner, professor of neurology, from Lund University. “What’s particularly exciting is that we’ve managed to translate laboratory findings into clinical application.”  Four-way crossover study The study included 22 patients with protracted and complicated Parkinson’s disease and L-dopa-induced dyskinesia. In the four-way crossover study, patients were given a single tablet of placebo and eltoprazine 2.5, 5 and 7.5 mg, alongside a challenge dose of levodopa that was 1.5 times that of their usual L-dopa dose. It was found that a 5 mg and 7.5 mg dose of eltoprazine both significantly reduced the patients’ dyskinesia. At the same time, the preparation had no adverse impact on the anti-Parkinsonian effects of the L-dopa treatment. Other than a few patients having some transient episodes of nausea, dizziness and other minor symptoms the treatment was well tolerated. “The treatment seems to be tolerated well by most Parkinson’s patients and counteracts L-dopa-induced dyskinesia via a new mechanism of action,” says Professor Svenningsson. “If our initial findings can be confirmed, this type of therapeutic principle can be of immense clinical benefit to a particularly vulnerable patient group.” Since the 1990s Even though eltoprazine has been around since the 1990s, it still has not been registered, and the combination study reported here was done on the initiative of the lead investigators themselves. The study was partly financed with a grant from the Michael J. Fox Foundation for Parkinson's research. Recently, however, the rights to eltoprazine were acquired by the US biotechnology company Amarantus BioScience Holdings, Inc. The compound is now advancing into a larger scale, longer duration study to evaluate the full treatment effect of eltoprazine in Parkinson’s patients with L-dopa-induced dyskinesia. Professor Svenningsson is affiliated to Karolinska Institutet's Department of Clinical Neuroscience, and to the Center for Molecular Medicine. He is also a specialist physician at the Karolinska University Hospital.  View our press release about this study Publication Eltoprazine counteracts L-dopa-induced dyskinesias in Parkinson's disease: A dose-finding study Per Svenningsson, Carl Rosenblad, Karolina af Edholm Arvidsson, Klas Wictorin, Charlotte Keywood, Bavani Shankar, David A. Lowe, Anders Björklund, Håkan Widner Brain – A Journal of Neurology, first online 10 February 2015

Karolinska Institutet and Novo Nordisk today signed a collaboration agreement in the field of diabetes. The programme will be fully funded by Novo Nordisk. In the new international post-doctoral fellowship programme, a total of 12 post-doctoral researchers will be offered a three-year grant to support their research primarily within the field of diabetes and metabolism. The research will be performed at Karolinska Institutet in Stockholm, Sweden, but there will also be possibility for research exchange performed at Novo Nordisk Research and Development in Denmark. “Novo Nordisk is the world leader in diabetes research and insulin, and this initiative is of strategic importance both to them and to us,” said Professor Anders Hamsten, vice-chancellor at Karolinska Institutet. “The agreement creates a unique opportunity for recruiting young diabetes researchers to Karolinska Institutet. In a comment to the collaboration agreement, Mads Krogsgaard Thomsen, executive vice president and chief science officer at Novo Nordisk, said: “Together, we will train scientists in exploring basic diabetes research and translating this into new potential treatments for patients. Building upon the unique academic and clinical tradition at Karolinska Institutet and our company’s excellence in research and development, the collaboration holds great potential to stimulate innovation and ultimately to improve the lives of the patients”. Novo Nordisk has research and development facilities in Denmark, US, China and India. More than 7,000 employees are involved in research and development activities, many of them working in partnerships with external biotech and academic researchers. “This agreement is yet another example of Karolinska Institutet’s ambition to strengthen collaboration with the business community, in this case Novo Nordisk, one of the leading pharmaceutical companies in the Nordic region,” said Professor Hans-Gustaf Ljunggren, dean of research at Karolinska Institutet. A joint steering committee with members from both Karolinska Institutet and Novo Nordisk will oversee the programme and will be responsible for recruiting researchers. The first four fellows in the programme are expected to start in the autumn of 2015.

Recent gut and urinary tract infections may curb the risk of developing rheumatoid arthritis, suggests a new study from Karolinska Institutet published online in the journal Annals of the Rheumatic Diseases. According to the researchers, one possible explanation could lie in the way in which these infections alter the types of bacteria resident in the gut (microbiome). The research team set out to look at the impact of different types of infection on the risk of developing rheumatoid arthritis in almost 6500 people living in south and central Sweden. Of the entire sample, 2831 had been newly diagnosed with rheumatoid arthritis between 1996 and 2009. The remaining 3570, who were randomly selected from the population, were healthy, but matched for age, sex, and area of residence with the patients. The average age of all participants at study entry was 52, and 7 out of 10 of them were women. All participants were asked whether they had had any gut, urinary tract, or genital infections in the preceding two years. They were also asked if they had had prostatitis (inflamed prostate), or antibiotic treatment for sinusitis, tonsillitis/other throat infection, or pneumonia during this time. Significantly lowered risk  Gut, urinary tract, and genital infections within the preceding two years were each associated with a significantly lowered risk of developing rheumatoid arthritis: 29 percent, 22 percent, and 20 percent, respectively. Further, having all three types of infection in the preceding two years was linked to a 50 percent lower risk, after taking account of influential factors.  By contrast, no such associations were found for recent respiratory infections and pneumonia. Factoring in smoking and socioeconomic background made no difference to the overall findings. However, since this is an observational study researchers point out that no definitive conclusions can be drawn about cause and effect. Lead author of the current study is Maria Sandberg, PhD, at Karolinska Institutet’s Institute of Environmental Medicine . The work was financially supported by grants from the Swedish Medical Research Council, the Swedish Research Council for Health, Working Life and Welfare, the AFA foundation, Vinnova, King Gustaf V’s 80-year foundation, the Swedish Rheumatic Foundation, and the Swedish Foundation for Strategic Research.  This news article is an adapted version of a press release from BMJ Journals. Publication Recent infections are associated with decreased risk of rheumatoid arthritis –a population-based case-control study Maria EC Sandberg, Camilla Bengtsson, Lars Klareskog, Lars Alfredsson, Saedis Saevarsdottir Annals of the Rheumatic Diseases, online first 5 February 2015,  doi 10.1136/annrheumdis-2014-206493

For low-income countries it is necessary to improve national research quality and capacity, and one way of doing this is through partnership with universities in high-income countries. However, the benefit of this kind of academic collaboration is mutual, according to the authors of a recent article in PLOS Medicine, in which they present the long-term partnership between Karolinska Institutet and Makerere University in Uganda. The collaboration between Karolinska Institutet and Makerere University started in 2001 and includes amongst other things the possibility for students to receive a novel joint PhD degree from both universities.  To date, 28 such joint degrees have been awarded. In all, the partnership has resulted in 44 graduated PhD students, of which 11 were from Sweden and 33 from Uganda, and over 500 peer-reviewed articles have been published in scientific journals. “The program makes it possible for PhD students to spend most of their time at the home university, travelling abroad not more than two or three months per year”, said Stefan Peterson, Professor of Global Health at Karolinska Institutet. “This has been beneficial to students with young children, and has served to minimize so called brain drain from Uganda. All Ugandan PhD graduates have remained in the country and thirteen of them have embarked on postdoc training.” Ugandan health system priorities This collaboration effort was enabled by core support from the Swedish Sida, and has mainly addressed Ugandan health system priorities. It has resulted in policy and practice reforms concerning improved mother and child health care in Uganda, also benefitting other African countries by means of WHO and UNCEF policy changes. “The research projects have focused on everything from mental health to Malaria”, said Stefan Peterson. “We are just starting a new study on diabetes and health systems, where the Swedish health system will learn from the Ugandan how to use community resources and expert patients to change lifestyles, rather than going to your GP.” According to Stefan Peterson, Sweden has a unique possibility through joint PhDs to contribute to a sustainable global development by supporting PhD education focusing on local problem issues in low-income countries and global health issues. This will also to benefit Sweden: “The world is one, and Swedish students, lecturers and scientist have a lot to learn”, said Stefan Peterson. “Not only Sida and the Swedish Foreign Ministry can benefit, but the Ministry of Higher Education as well, and should fund these kind of efforts. “ More about Karolinska Institutet's collaboration with Uganda Publication Enabling Dynamic Partnerships through Joint Degrees between Low- and High-Income Countries for Capacity Development in Global Health Research: Experience from the Karolinska Institutet/Makerere University Partnership Nelson Sewankambo, James K. Tumwine, Göran Tomson, Celestino Obua, Freddie Bwanga, Peter Waiswa, Elly Katabira, Hannah Akuffo, Kristina Persson, Stefan Peterson PLOS Medicine, online 3 February 2015, doi: 10.1371/journal.pmed.1001784

Three new facilities for single cell biology are being set up at SciLifeLab in Stockholm and Uppsala during spring 2015. The new facilities will render technological advances in Sweden and abroad widely available to the Swedish scientific community, with the goal for the region to become world leading in advanced molecular single cell analyses. Advances in cell sorting and molecular analyses now enable researchers to comprehensively describe properties and functions of individual cells. This is in contrast to conventional biochemistry and molecular biology, which focuses on analyses of whole tissue samples and whole microbial populations or communities. The three new single cell-facilities will be integrated in the SciLifeLab national platform Functional Genomics. The facilities build on unique expertise that will allow Swedish researchers to capitalize on recent technological advances to characterize individual cells at genomic, transcriptomic, and proteomic levels. The aim is to provide new insights into heterogeneity and division of labor within tissues or communities of cells from all domains of life. “Single cell genomics can be applied to understand the heterogeneity of tumors, to explain how genetically identical cells may show distinct behavior, and to explore the vast, uncharacterized microbial landscape. Therefore, these technologies have the potential to revolutionize biology and medicine.” says Sten Linnarsson, Senior Researcher at Karolinska Institutet and Platform Director of the Eukaryotic Single-Cell Analysis facility. Read more here

Karolinska Institutet is to set up its own research base in Hong Kong. This is made possible by a donation of USD 50 million, equivalent to SEK 400 million made by Hong Kong-based businessman Ming Wai Lau. The Ming Wai Lau Center for Regenerative Medicine will comprise two nodes, one in Stockholm and one in Hong Kong, and will allow scientists from Hong Kong, China, and around the world to work together in an independent research environment under the auspices of Karolinska Institutet. The Center’s research focus will be on three major disease areas in which Karolinska Institutet and several Hong Kong universities possess unique expertise. One of its objectives is to use stem cell technology to rebuild damaged tissue, focusing, for example, on heart tissue damaged by infarction, spinal injury and finding a cure for Parkinson’s disease, and on repairing a damaged liver using stem cell transplants. “This exceedingly generous donation from Ming Wai presents unprecedented opportunities to do groundbreaking research in these extremely important disease areas,” says Professor Anders Hamsten, vice-chancellor of Karolinska Institutet. “The new center will provide our university with a pathway to critically important knowledge and bring us closer to key partners.” The donor Mr. Ming Wai Lau is the Chairman and Chief Executive Officer of Chinese Estates Holdings Ltd and Vice Chairman of the Bauhinia Foundation Research Centre. He holds a Master of Laws and a PhD from the London School of Economics and King’s College London, with his doctoral thesis being published as a book by Oxford University Press in 2011. He is also a registered attorney in the State of New York and in 2014 was a visiting lecturer at Harvard Law School, Boston, USA. Ming Wai Lau is also active in public affairs.   Read more in a press release.  

Karolinska Institutet has withdrawn the application to the Swedish Research Council approved last month for the recruitment of Professor Nils-Göran Larsson from the Max Planck Institute for Biology of Ageing in Cologne, Germany.  The application did not meet the formal requirements, a mistake that the university discovered just before receiving and signing the contract. On 15 January, the Swedish Research Council (VR) decided to grant Karolinska Institutet a total of 100 million kronor to finance the recruitment of Professor Larsson; this sum has now been retracted since KI drew attention to the fact that the formal application requirements had not been met. Since 2007, when Professor Larsson was appointed director of the Max Planck Institute in Cologne, he has been on 80 per cent leave from his duties at KI in accordance with the Max Planck Institute’s regulations for side-line occupations. VR allows temporary employment of up to 20 per cent of full time at KI (as a visiting professor) under the current programme for the international recruitment of outstanding researchers, but not permanent employment (even if the employee is on 80 per cent leave). KI has therefore withdrawn the application in question and regrets having failed to fully heed VR’s regulations at the time of application.  

Two cases of suspected scientific misconduct involving Paolo Macchiarini, surgeon and visiting researcher at Karolinska Institutet, are now under investigation. In one of the cases, the vice-chancellor has tasked an external expert to issue a statement on the matter, which although expected in mid-February, could be delayed a few weeks given the volume of material. The statement will be passed to the vice chancellor, who will then announce his decision on the matter.  For the second of the two cases involving Professor Macchiarini, the vice-chancellor has requested a pronouncement from Karolinska Institutet’s Ethics Council. This too is expected in February and will also be submitted to the vice-chancellor. The Ethics Council has also been asked by the vice-chancellor to issue a statement on a report against Dr Karl-Henrik Grinnemo, who is affiliated to Karolinska Institutet and who is one of the four doctors behind the allegations against Professor Macchiarini. This third case concerns suspected irregularities relating to a grant application that were reported by a colleague of Professor Macchiarini. The Ethics Council’s statement is expected within the coming few weeks.  The Higher Education Ordinance requires an institute to investigate suspected scientific misconduct should it receive a report of such. According to Karolinska Institutet’s regulations, it is the duty of the vice-chancellor to investigate a report of this kind and decide on it either by passing it on without further action, or, if misconduct is confirmed, by taking appropriate action. Karolinska Institutet does not wish to anticipate the outcome of these investigations and will pass no comment on them until they have been concluded. Some press reports on these cases: New York Times: "Leading Surgeon Is Accused of Misconduct in Experimental Transplant Operations". Nature: "Investigations launched into artificial tracheas".

A research article published in Science presents the first major analysis based on the Human Protein Atlas, including a detailed picture of the proteins that are linked to cancer, and the targets for all approved drugs on the market. The Human Protein Atlas, launched in November 2014, is an open source tissue-based interactive map of the human proteome. Based on 13 million annotated images, the database maps the distribution of proteins in all major tissues and organs in the human body. As an open access resource, it is expected to help drive the development of new diagnostics and drugs, but also to provide basic insights in normal human biology. In the newly published Science article, over 90 percent of the approximately 20,000 protein coding genes in humans were analysed. The study shows that some proteins are present in all tissues and others in specific organs such as heart, liver and blood. This information is important for the pharmaceutical industry. The 618 proteins that act as targets of all approved drugs on the market were analysed specifically, and it was shown that 70 percent of these were excreted or in the cell membrane. Present in all tissues The information can be used to explain how different drugs work and why some of them have side effects. For example, the analysis showed that 30 percent of the targets are present in all tissues. This can explain why certain drugs have side effects. The researchers hope that the results of the analysis can be used to develop improved drugs in the future. “It is such a great time to do research", said study co-author Jan Mulder, researcher at the Department of Neuroscience at Karolinska Institutet and affiliated to the national research facility Science for Life Laboratory (SciLifeLab). "By completing the human protein atlas we  are now able to retrospectively look at drug targets and their distribution in normal tissue. The next step would be to utilize this data and other global expression data that is rapidly being generated to find new and better targets for many of the diseases humanity struggles with.” This study was carried out by researchers in Sweden at Royal Institute of Technology (KTH), Uppsala University, Karolinska Institutet, Chalmers University of Technology, Lund University, Stockholm University, and SciLifeLab.  It was funded by the Knut and Alice Wallenberg Foundation.  The research was led by Mattias Uhlén at KTH and SciLifeLab. Learn more about the Human Protein Atlas View a press release from KTH about the findings Publication Tissue-based map of the human proteome Mathias Uhlén, Linn Fagerberg, Björn M Hallström, Cecilia Lindskog, Per Oksvold, Adil Mardinoglu, Åsa Sivertsson, Caroline Kampf, Evelina Sjöstedt, Anna Asplund,  IngMarie Olsson, Karolina Edlund, Emma Lundberg, Sanjay Navani, Cristina Al-Khalili Szigyarto, Jacob Odeberg, Dijana Djureinovic, Jenny Ottosson Takanen, Sophia Hober, Tove Alm, Per-Henrik Edqvist, Holger Berling, Hanna Tegel, Jan Mulder, Johan Rockberg, Peter Nilsson, Jochen M Schwenk, Marica Hamsten, Kalle von Feilitzen, Mattias Forsberg, Lukas Persson, Fredric Johansson, Martin Zwahlen, Gunnar von Heijne, Jens Nielsen, Fredrik Pontén Science, online  23 January 2015, doi: 10.1126/science.1260419

The Swedish Research Council (VR) has decided to grant Karolinska Institutet a total of 100 million kronor to finance the recruitment of Professor Nils-Göran Larsson from the Max Planck Institute for Biology of Ageing in Cologne, Germany. The funds will be distributed over a period of ten years. Nils-Göran Larsson has worked at the Department of Laboratory Medicine, Karolinska Institutet for several years. His research concerns mitochondrial function and dysfunction in the healthy and sick, with a particular emphasis on ageing. His work at Karolinska Institutet is expected to contribute to the establishment of strong translational research environments in a clinical setting.  VR has approved three of 44 submitted applications to finance the international recruitment of outstanding researchers. The remaining funds will go to Uppsala and Stockholm universities.

A study of twins conducted by Swedish and American investigators shows that our environment, not our heredity, plays the starring role in determining the state of our immune system, the body’s primary defense against disease. This is especially true as we age, the study indicates. The findings are being published in the journal Cell. Much has been made of the role genes play in human health. Stunning advances in gene-sequencing technologies have caused many scientists to focus to minute variations in the genome, in the hope of predicting people’s future health. Such studies have revealed genetic contributions to health outcomes. But, with some notable exceptions, very few of those individual genetic variants seem to contribute much in particular health conditions. To determine nature’s and nurture’s relative contributions, scientists at Sweden’s Karolinska Institutet and Science for Life Laboratory (SciLifeLab) together with colleagues at Stanford University in the United States turned to a century-old method of teasing apart environmental and hereditary influences: They compared pairs of monozygotic twins — best known to most of us as “identical — and of dizygotic, or fraternal, twins. Monozygotic twins inherit the same genome. Despite inevitable copying errors when cells divide, which cause numerous tiny genetic divergences to accumulate between monozygotic twins over time, they remain almost 100 percent genetically identical. Dizygotic twins are no more alike genetically than regular siblings, on average sharing 50 percent of their genes. Sophisticated laboratory methods Because both types of twins share the same environment in utero and usually share the same environment in childhood, they make excellent subjects for contrasting hereditary versus environmental influence. For the new study, the researchers recruited 78 monozygotic-twin pairs and 27 pairs of dizygotic twins from the registry and then applied sophisticated laboratory methods to participants’ blood samples to measure more than 200 distinct immune-system components and activities. “Examining differences in the levels and activity states of these components within pairs of monozygotic and dizygotic twins, we found that in three-quarters of the measurements, non-heritable influences such as previous microbial or toxic exposures, vaccinations, diet and dental hygiene trumped heritable ones when it came to accounting for differences within a pair of twins”, said lead author Petter Brodin, MD, PhD at SciLifeLab and Karolinska Institutet’s Department of Medicine, Solna. “This environmental dominance became more pronounced when divergences between young identical twins, under the age of 20, were compared to those much older twins, ages 60 and up. Even traits that correlated quite strongly within these pairs in youth often lost that correlation in advanced age.” The research team also observed considerable environmental influence over the quantities of antibodies produced in members of twin pairs who had been vaccinated for influenza. While many previous studies have suggested a powerful genetic component in vaccine responsiveness, Brodin et al noted that those studies typically were performed in very young children who had not yet undergone the decades of environmental exposure that appears to reshape the immune system over time. Chronic carriers of cytomegalovirus In a striking example of the immune system’s plasticity, the study found that the presence or absence of a single chronic, viral infection could have a massive effect on the system’s composition and responsiveness. Three out of five Americans and as many as nine out of 10 people in the developing world are chronic carriers of cytomegalovirus, which is dangerous in immune-comprised people but otherwise generally benign. In 16 of the 27 monozygotic twin pairs participating in the study, one member of the pair had been exposed to cytomegalovirus but the other had not. For nearly 60 percent of all the features measured, cytomegalovirus’s presence in one twin and absence in another made a big difference. “Non-heritable influences, particularly microbes, seem to play a huge role in driving immune variation,” said senior author Mark Davis, PhD, professor of microbiology and director of Stanford’s Institute for Immunity, Transplantation and Infection. “At least for the first 20 or so years of your life, when your immune system is maturing, this amazing system appears able to adapt to wildly different environmental conditions. A healthy human immune system continually adapts to its encounters with hostile pathogens, friendly gut microbes, nutritional components and more, overshadowing the influences of most heritable factors.” The work was funded principally by the National Institutes of Health, the Howard Hughes Medical Institute, the Wenner-Gren Foundation, and the Sweden-America Foundation. More about this study in a press release from Stanford University  Publication Variation in the human immune system is largely driven by non-heritable influences Petter Brodin, Vladimir Jojic, Tianxiang Gao, Sanchita Bhattacharya, Cesar J Lopez Angel, David Furman, Shai Shen-Orr, Cornelia L Dekker, Gary E. Swan, Atul J Butte, Holden T Maecker, Mark M Davis Cell online 15 January 2015