KI News

A team of Swedish researchers lead by Agneta Richter-Dahlfors at Karolinska Institutet has developed a cellulose detection system that is non-invasive and no-destructive. Detection of cellulose is very important for recycling and developing clean, renewable energy however, until now it has been very difficult, requiring dangerous chemicals and specialized equipment. Cellulose is a major component of all plant matter and is one of the most abundant and widely used molecules on the planet. It is a long, strong polymer that has a number of diverse uses in textiles and packaging. It can also be broken down into biogas, a process that could ultimately release society from a strong dependence on fossil fuels. The problem with cellulose is that it is rarely found in a pure form and the quality can vary a lot. Not being able to accurately assess the quality and purity is making recycling and manufacturing processes more difficult and less efficient. This leads to unnecessary waste in recycling which is costly and damaging to the environment, it also means that it is difficult to monitor the quality of the breakdown of cellulose to biogas. Non-toxic molecule can provide a simple readout of quality The Swedish research team have synthesized a non-toxic molecule that can be easily applied to different forms of cellulose and provide a simple, optical readout of the quality. This could be used routinely and safely at any part of the cellulose-processing pipeline, giving multiple options for deployment and optimization. Current methods of quantifying cellulose are technically very demanding and require harsh pre-treatments with strong and corrosive chemicals in order to degrade the polymers for analysis. The traditional methods also suffer from difficulties in the scale up process owing to the large quantities of dangerous chemicals required and the scarce access to complex analysis machinery. "The next step for this technology is to make it available to the different industries that rely on cellulose as well as creating new, safe detection systems that reduce the reliance on dangerous chemicals and improve the quality efficiency of the recycling process", says Agneta Richter-Dahlfors. This study was made possible by funding from Carl Bennet AB, the Erling-Persson Family Foundation and the European Research Council Publication “Nondestructive, real-time determination and visualization of cellulose, hemicellulose and lignin by luminescent oligothiophenes” Ferdinand X. Choong,  Marcus Bäck,Svava E. Steiner,Keira Melican, K. Peter R. Nilsson, Ulrica Edlund & Agneta Richter-Dahlfors Scientific Reports, 19 october 2016. Doi:10.1038/srep35578  

It has recently been decided where the research groups and other personnel are to be placed in Biomedicum, the new research lab on Karolinska Institutet’s Solna campus, which is scheduled for completion in 2018. The focus can now shift from the building process and placement of research groups to the research itself, says Pontus Aspenström, who chairs Biomedicum’s Chairpersons’ Team. Only a narrow passage separates Biomedicum and Aula Medica, which stand shoulder-to-shoulder on the Solnavägen side of the campus. It is here that Pontus Aspenström talks about the project in which he has been involved since the start five years ago. He was once a vocal advocate for the researchers, but since 1 June has been chairing Biomedicum’s Chairpersons’ Group. For six months he will have overall responsibly for making sure that things get done according to plan before relinquishing the rotating chair to his successor. “You really have to think, ‘How can we do this as well as possible for as many as possible?’” he says. “It might not appeal a hundred per cent to everyone but we’ve tried to minimise the pitfalls. We can’t afford to trip up now that we’re so close.” Preparations and further planning As one aspect of the preparations, the researchers from the five departments set to occupy Biomedicum were asked to state their needs as regards infrastructure and lab equipment, as well as which groups they would like to be placed in close proximity to. “We’ve recently been planning very actively and tried to bring all the groups into line with each other to make sure that all departments and researchers are happy before the big move,” explains Professor Aspenström. “Now that this has been decided, everyone will be meeting to discuss and sort out how they want to optimise their local environments.” One of the concepts for the building is the “indoor park” idea. By constructing verdant environments, the building will compensate for the shrubbery and trees that occupied the site before building commenced. “I think it’ll be pretty awesome,” says Professor Aspenström. “It’ll be something new in contrast with the old, classic KI.” First scientific conference on 21 October There will also be a lot of shared space and ‘alleyways’ between the previously segregated departments in order to help bring people together. “It’s a pretty theory, but we really hope that it’ll work out in practice too.” The focus is now shifting from the building process and placement of research groups to the actual research. There are already joint activities in place and the first scientific conference for Biomedicum is scheduled for 21 October. “It’s now in our and the researchers’ hands to do the world-leading research that we’re actually here to do,” says Professor Aspenström.   Text: Mårten Göthlin Photo: Gustav Mårtensson A longer article appeared in KI Bladet 4/2016 (in Swedish only). Biomedicum in brief Biomedicum will bring together much of the experimental research conducted on Karolinska Institutet’s Solna campus under one and the same roof. Since the laboratory equipment is both advanced and costly, it must be possible for more than one group to use it. The aim is to encourage fruitful collaborations between research groups in both basic and clinical research. Construction started in 2013, with occupancy scheduled for 2018.

Karolinska Institutet's yearly installation ceremony was held Thursday 13 October. New professors were installed, adjunct professors and visiting professors were warmly welcomed to KI, and this year's receivers of academic prizes and awards were celebrated. New professors at KI For further reading on the new professors, please visit this page. New visiting professors at KI Lars Fugger – Neuroimmunology Mika Gissler – General Practice Eystein Sverre Husebye – Endocrinology Matti Hämäläinen – Magnetoencephalography Methods Development Veikko Tapani Jousmäki – Magnetoencephalography Methods Development Henrik Larsson – Epidemiology Outimaija Mäkitie – Paediatric Endocrinology Robert Oostenveld – Magnetoencephalography Methods Development Lennart Svensson – Molecular Virology Unnur Valdimarsdóttir – Epidemiology Riitta Veijola – Paediatric Diabetology Per Wester – Clinical Stroke Research Cecilia Williams – Experimental Oncology Biao Xu – Public Health Epidemiology New adjunct professors at KI Maria Bejarano – Infection Biology Anca Catrina – Rheumatology Braunschweig Frieder – Cardiology Annika Tibell – Medical Ethics Tomas Wester – Paediatric Surgery Learn more about all the professors at Karolinska Institutet here. Prices and awards highlighted during the ceremony Karolinska Institutet´s Grand Silver Medal, awarded to Anders Ekbom, Ingemar Ernberg, Agneta Nordberg, Bengt Norrving och Elisabeth Olsson. The Karolinska Institutet Prize for Research in Medical Education, awarded to Brian Hodges. Karolinska Institutet´s Pedagogical Prize, awarded to Dulceaydee Norlander Gigliotti.  The Dimitris N. Chorafas Prize, awarded to Alessandro Furlan. The Erik K. Fernströms Prize, awarded to Rickard Sandberg. The Med dr Axel Hirsch Prize, awarded to Mats Wahlgren. The Håkan Mogren Prize, awarded to Peter Berggren. The Lennart Nilsson Award, awarded to Alexey Amunts

Bob Dylan has been awarded this year’s Nobel Prize in literature, much to the delight of his fans around the world – including the researchers at Karolinska Institutet who have been known to sneak Dylan quotes into their medical articles. For having “created new poetic expressions within the great American song tradition”, Bob Dylan is the first ever musician to have been awarded the literature prize. When KI’s internal magazine KI Bladet wrote about a group of researchers back in 2014 who competed over who could smuggle the most Dylan quotes into their academic papers, it became world news. Carl Gornitzki, librarian at Karolinska Institutet University Library and a huge Dylan fan, was the one who let on about the internal contest. He is overjoyed with today’s announcement from the Swedish Academy. “Many professors at KI liked Dylan, but that he won the prize is unexpected but great news,” he says. “The Americans haven’t won the literature prize for a long time, so it no doubt means a lot to them to have a major icon bring it home.” Eddie Weitzberg, professor at the Department of Physiology and Pharmacology is lyrical: “I’m glowing from head to toe,” he says. “I’ve always thought he should get it and this is a great day for culture. But he’s not an easy man and the question is whether he’ll show up to receive the prize. It reminds me of the line from Is your love in vain where he sings “I have dined with kings, I’ve been offered wings, and I’ve never been too impressed.” However, there has long been much speculation about whether Bob Dylan, 74, has been in the running for the literature prize, and only a few experts have thought that pop music could be so rewarded by the Swedish Academy. But today they had their answer. Jon Lundberg, professor at the Department of Physiology and Pharmacology, is also a big Dylan fan: “A minute before they announced the winner I thought I hope it’s Bob Dylan. And when they said it, I ran and called my colleague Eddie. I got goose pimples and wondered if that meant he’ll be coming to Stockholm.” Who’s leading your Dylan contest? “It’s a dead heat between me, Eddie Weitzberg and Jonas Frisén. Is there any line or lyric that makes Bob Dylan a particularly worthy Nobel laureate? “Yes, I’d say “I was so much older then, I’m younger than that now” from the song My back pages. It’s like you’re small, but know all. And it’s so neatly put too.” The Nobel Prize in literature has never been awarded to a musician before. But as Dylan says, the times they are a-changing. Text: Susanna Forsell Photo: Gustav Mårtensson

Around six per cent of Stockholmers are thought to have chronic kidney disease, roughly as many as those suffering from type 2 diabetes. There is, however, a major difference between the two: chronic kidney disease is in many ways invisible, and most sufferers are unaware of the fact they have it. This according to researchers from Karolinska Institutet, who have studied the incidence of the disease amongst 1.3 million patients in Stockholm. The study is published in Nephrology Dialysis and Transplantation. Sufferers of chronic kidney disease experience a gradual deterioration of kidney function. In its early stages, the symptoms are not that clear, although high blood pressure, anaemia and disruption of the calcium-phosphate balance are common. Eventually, the disease is associated with cardiovascular disease and death. Although in the later phases of the disease patients require dialysis or a kidney transplant to survive, if it is caught early enough there are good treatment options available. However, there is a serious lack of knowledge concerning diagnosis and treatment and how the patients are to be taken care of by the healthcare services. When researchers at Karolinska Institutet analysed the results from clinical laboratories in Stockholm County, they noticed that around six per cent of the 1.3 million people examined had chronic kidney disease; however, most of them had not received a diagnosis and were unaware of their problem. Kidney disease turned out to be as common as type 2 diabetes and often has co-morbidity with other chronic diseases, such as hypertension, diabetes and cardiovascular disease. “The study shows up a lack of awareness about how common the disease is,” says Juan-Jesus Carrero, researcher at the Department of Clinical Sciences, Intervention and Technology. “Caregivers need such knowledge to be able to treat and prevent serious, life-threatening kidney failure and to give the correct drug doses. There’s much room for improvement in the health services when it comes to detecting and treating the disease.” The presence of albumin in the urine is a good measure of chronic kidney disease Current guidelines say that the presence of albumin in the urine is a good measure of chronic kidney disease and enough to warrant referrals to a nephrologist. The study shows that many people with albumin in their urine were not referred or diagnosed with chronic kidney disease. Only one in four people with chronic kidney disease had seen a kidney specialist. “By making caregivers more aware of the disease and how chronic kidney disease can be treated in its early phases, we’d make considerable heath gains for society,” claims Professor Carl-Gustaf Elinder, consultant for the Stockholm health administration and Peter Barany, acting clinical manager at Karolinska University Hospital, both of whom are co-authors of the study. The study was financed with grants from the Stockholm County Council, the Swedish Heart and Lung Foundation, the Swedish Research Council, Dalarna University and the Martin Rind Foundation. It was conducted at Karolinska Institutet in collaboration with Johns Hopkins in the USA. Publication “Prevalence and recognition of CKD in Stockholm healthcare” Alessandro Gasparini, Marie Evans, Josef Coresh, Morgan E. Grams, Olof Norin, Abdul R Qureshi, Björn Runesson, Peter Barany, Johan Ärnlöv, Tomas Jernberg, Björn Wettermark, Carl G Elinder and Juan-Jesus Carrero. Nephrology Dialysis Transplant, online 13 oktober 2016, doi: 10.1093/ndt/gfw354  

(The York University press release) ‘Owning’ an obese body produces significantly lower body satisfaction for females than males, scientists have found. In the first study of its kind investigating healthy individuals and their brain activity when perceiving themselves as either slim or obese, psychologists at the University of York and Karolinska Institutet in Stockholm found that the way we perceive our bodies directly triggers neural responses which can lead to body dissatisfaction. To create a sense of illusory body ownership, participants wore a virtual reality headset and observed a video of an obese or slim body from a first person perspective, so when looking down the body appeared to belong to them. Scientists then prodded the participants’ torso with a stick in synchronisation with the video, eliciting a vivid illusion that the stranger’s body was their own. Monitoring brain activity in an fMRI scanner, scientists found a direct link between activity in the parietal lobe of the brain – relating to body perception – and the insular and anterior cingulate cortex, which controls subjective emotional processes such as pain, anger or fear. Such research helps to shed light on why sufferers of eating disorders such as anorexia nervosa can be affected by a distorted perception of their body as overweight, when in reality this is biologically inaccurate. Investigating healthy individuals allows researchers to examine the link between perception and emotion without the possibility that body starvation could affect biological results, as is the case when studying those with eating disorders. Dr Catherine Preston, Lecturer in York’s Department of Psychology and lead author of the study says: “In today’s Western society, concerns regarding body size and negative feelings towards one’s body are all too common. However, little is known about the neural mechanisms underlying negative feelings towards the body and how they relate to body perception and eating-disorder pathology. “This research is vital in revealing the link between body perception and our emotional responses regarding body satisfaction, and may help explain the neurobiological underpinnings of eating-disorder vulnerability in women.” Henrik Ehrsson, Associate Professor at Karolinska Institutet and co-author of the study, adds: “We know that woman are at greater risk at developing eating disorders than men, and our study demonstrates that this vulnerability is related to reduced activity in a particular area of the frontal lobe – the anterior cingulate cortex – that is related to emotional processing.” Dr Preston hopes to follow up these findings with subsequent research investigating how emotions could affect body perception. Publication ”Illusory obesity triggers body dissatisfaction responses in the insula and anterior cingulate cortex”,  Catherine Preston, Henrik Ehrsson Cerebral Cortex online: 12 oktober 2016, doi:10.1093/cercor/bhw313.

The Medical Students’ Union (MF) building on the Karolinska Institutet Solna campus desperately needs renovating, at an estimated cost of SEK 40 million. The union is now raising money to secure the building’s – and its own – future. The MF building was last renovated in 1985, and is now in dire need of a facelift. Top priorities are to replace windows, renovate the auditorium and upgrade the sound equipment.  “If the building isn’t renovated, it will eventually be unusable, in which case what becomes of the union is anyone’s guess,” says MF chairperson Frida Hellström. To deal with the problem, MF arranged an alumni get-together on a Sunday afternoon in early October to urge former KI students to empty their pockets – one of many ways that the union is hoping to finance the necessary work.  “Students need a place to meet” Around fifty guests gathered at the stage to listen to firebrand speakers and enjoy the antics of Corpus and Flix, the union’s spex troupes. One of the speakers was Annika Östman Wernerson, dean of higher education at KI. “I hope it’s only too obvious that former students of KI are serious about the demand for a functional, modern union building,” she says. “KI’s many programmes bring together students from around the country and all over the world, and they need a place to meet.”  Mandatory union membership was abolished in 2010, and since then the unions’ finances have shrunk, leaving them dependent on donations from foundations, companies and private individuals to keep their heads above water. “We realise, of course, that our alumni can’t bankroll the entire renovation project,” says Ms Hellström. “But their interest and support mean that we can approach companies and foundations and show them that this is something that everyone at KI and in MF wants.” Few donations, but still hopeful The audience mainly comprised veterans and older alumni, including one-time fellow-students Göran Sterky and Ingvar Liljefors, who sat flicking through a seemingly faded yearbook from 1954, the same year they were at the official opening of the union building.  “Of course they need the union building,” says Mr Sterky. “It provides space for activities and has a good gasque room in the basement for dinner parties. But I think this fundraising drive won’t go well. I mean, there aren’t any companies here, are there?” Even though only a few donations from private individuals have been made, Professor Wernerson remains upbeat: “Contributions from KI alumni are important, not only in terms of the money itself but also because they send out signals to others who might want to donate to a decent, functional union building.” Text and photo: Susanna Forsell

The Undergraduate Awards (UA) is an annual international programme that selects the best degree papers in the natural sciences, humanities, business and art. This year, six students of medicine, biomedicine and biomedical laboratory science at Karolinska Institutet have qualified as Highly Commended Entrants, which means that their papers are in the top ten per cent of their category. The students have now been invited to a UA congress in Dublin, Ireland. The competition was tough: 5,514 entries from students at 244 universities in 121 countries, all written and English and graded A in accordance with the criteria. Since KI has no such grading system, the study programmes selected their own papers; a total of seventeen were submitted by KI for assessment. Highly Commended Entrants from KI, 2016: Vidar Elsin, biomedicine Benjamin Heller Sahlgren, biomedicine Anna Arbman, biomedical laboratory science Linda Storbjörk, biomedical laboratory science Christine Lageborn, medicine Sara Meziani, medicine

On 7 October the Ming Wai Lau Centre for Reparative Medicine was inaugurated in Hong Kong. Researchers from around the world will be able to conduct research within regenerative medicine at the new facility with the future goal of being able to replace damaged or lost tissue. The centre is Karolinska Institutet’s first hub outside of Sweden. By establishing this node in Hong Kong, Karolinska Institutet (KI) is strengthening its research within regenerative medicine. ”This is a natural step for KI, given our ambition of continuing to be a leading international university in medical research. Hong Kong is a global hub for research and innovation and provides unique opportunities for collaboration and knowledge exchange. By establishing this new centre, we hope to take a significant step forward in an area that can have important future implications for human health,” says Karin Dahlman-Wright, Karolinska Institutet’s Acting Vice-Chancellor. Two nodes headed by KI The Ming Wai Lau Centre for Reparative Medicine will consist of two nodes, one in Stockholm and one in Hong Kong. Under KI's leadership, the centre will conduct basic research using technologies that are relevant for regenerative medicine. One of the primary goals is to develop new knowledge and tools to repair damaged or lost tissue. “We believe that people who are skilled in this area will be attracted by the new centre. Research today is all about partnerships, especially for newly established groups. Much of the best stem cell research today is being done in Asia, and KI wants to be a part of it,” says Ola Hermanson, scientific director of the new centre and researcher at KI’s Department of Neuroscience. The centre has been fully funded through a donation from the Hong Kong-based businessman Ming Wai Lau. 

Two research teams at Karolinska Institutet have identified the dopamine-producing cells in the midbrain of mice and humans. They have also developed a method of assessing the quality of in-vitro cultured dopamine-producing cells, which can be of great benefit to research on Parkinson’s disease. The results are published in the academic journal Cell. The embryonic development of the midbrain is of considerable interest to scientists hoping to find better forms of treatment for Parkinson’s disease. The symptoms of the disease are caused by the loss of dopamine-producing cells in the midbrain, which results in deterioration of motor function.  A treatment that does not yet exist but that the researchers are very hopeful about involves replacing lost dopamine-producing cells with new cells grown in the laboratory from stem cells. However, one hurdle that this research has faced is that relatively little is known about the human midbrain, which means that knowledge of the similarity between cultured and endogenous dopamine-producing cells is also scant. ”In order to learn more about this, we’ve used single-cell analysis to study gene activity in individual cells,” says Sten Linnarsson from the Department of Medical Biochemistry and Biophysics at Karolinska Institutet. ”We’ve identified and compared cultivated dopamine-producing cells with those of the human brain as well as mice.” The two research teams, led by Professor Linnarsson and Professor Ernest Arenas with doctoral students Gioele La Manno and Daniel Gyllborg, found 25 different types of cell, including formerly unknown subtypes of immature cell (radial glia), which give rise to specific kinds of neurons. One surprising discovery is that the in-vitro cell cultures had almost the same degree of diversity and complexity as the human midbrain. ”They form a similar composition to the one in the brain, but they’re not identical and probably don’t function as well,” says Linnarsson. ”The aim is to produce cultured cells that are as similar as possible to those developed in the brain.” The work of the two teams has also resulted in a method of assessing the quality of stem cell samples, which is achieved through painstaking comparison with cells observed in the embryo. The method is highly significant to the understanding of brain development, and more specifically to the ability to assess the quality of the cells that will one day be graftable into humans in international clinical trials. ”We need to know what we’re sticking into people’s brains,” says Professor Arenas. ”Until now, we’ve only been able to test a few markers in fetal dopamine-producing cells. Our new method creates brand new opportunities for quality-assessments and for research into Parkinson’s disease.” Can compare dopamine-producing cells from two species This is also the first time a method has been developed for comparing dopamine-producing cells from two species – humans and mice. Given that effectively all research in the field is done on mice, this provides scientists with a very important tool. ”It’s surprising just how similar human and mouse embryonic development is in terms of both cell types and gene activity,” says Professor Linnarsson. ”Our study can therefore be taken as evidence that research on dopamine cells in mice works.” The research was financed with grants from the EU Commission’s 7th Framework Programme for Research and Technological Development, the European Research Council, the Swedish Research Council and Karolinska Institutet Publication  “Molecular Diversity of Midbrain Development in Mouse, Human and Stem Cells” Gioele La Manno, Daniel Gyllborg, Simone Codeluppi, Kaneyasu Nishimura, Carmen Salto, Amit Zeisel, Lars E. Borm, Simon R.W. Stott, Enrique M. Toledo, J. Carlos Villaescusa, Peter Lönnerberg, Jesper Ryge, Roger A. Barker, Ernest Arenas, Sten Linnarsson Cell, published online 6 Oktober 2016, doi 10.1016/j.cell.2016.09.027

Knut and Alice Wallenberg Foundation (KAW) has granted SEK 143 Million for a period of five years to four research projects at Karolinska Institutet, considered to be of the highest international level, and potentially leading to future scientific breakthroughs. The principal applicants of these four projects are Patrik Ernfors, Katja Petzold, Nils-Göran Larsson and Sten Eirik Jacobsen. Project funding from KAW is granted primarily for basic research in the field of medicine, technology and the natural sciences. In all, the foundation has granted SEK 752 Million in project funding to 22 research projects in 2016. “The project grants are the largest annual funding made by the foundation. The grants go to cutting-edge independent research in Sweden. We want to give researchers the opportunity to try out new and bold ideas over an extended period,” says Peter Wallenberg Jr, Chairman of Knut and Alice Wallenberg Foundation, in a press release. Decomposition of pain into cell types Project: Decomposition of pain into cell types Grant awarded: SEK 17,175,000 over five years Principal applicant: Professor Patrik Ernfors, Department of Medical Biochemistry and Biophysics Over twenty-five per cent of people over the age of 20 have problems with pain; twenty per cent have chronic pain, and roughly 7 per cent disabling pain. Every day, Millions of people in Europe and around the world experience chronic pain, causing considerable suffering to them and great costs to society in terms of care, rehabilitation and loss of productive work. While acute pain often represents a normal sensory function of the nerve system to alert the body to possible damage, chronic pain is something altogether different. It is long-lasting and caused by the abnormal activity of sensory nerves owing to injury or inflammation.  Despite the many attempts made, no conceptually new form of pain relief has yet been developed. This is because the relationship between different kinds of nerves/neurons and pain is still unknown; because most studies on pain have been conducted on rodents with little knowledge of their relevance to humans; and, finally, because identical experiences of pain can have very different mechanical origins. In their project, Professor Patrik Ernfors and his colleagues will be exploiting the latest molecular, cellular and genetic technologies in an extensive, impartial strategy designed to fill these knowledge gaps.  The researchers hope to be able to identify the precise cellular origin of pain in different pain syndromes. Even though different pain syndromes seem similar as regards the experience of pain, they are likely caused by distinct cellular mechanisms. The researchers will also examine the relationship between the pain-signalling neurons in primates and their analogues in rodents, which could give results from research in rodents a clinical relevance. “We believe that our results will lead to a brand new start for the development of conceptually new drugs that target the pain cells that actually generate pain in various pain syndromes,” says Professor Ernfors. MicroRNA control of neural development: Dissecting biological function with atomic resolution Project: MicroRNA control of neural development: Dissecting biological function with atomic resolution Grant awarded: SEK 33,520,000 over five years Principal applicant: Assistant Professor Katja Petzold, Department of Medical Biochemistry and Biophysics Co-applicant: Assistant Professor Emma Andersson, Department of Biosciences and Nutrition In this project, the researchers, led by Assistant Professor Katja Petzold, are examining how a single microRNA (miRNA) can regulate the neural development of the brain. A single miRNA can control an entire network of different messenger RNAs (mRNAs), and thus fine tune protein levels. Despite the fact that over half of mRNA is regulated by miRNA, it remains a mystery how the miRNA “decides” what happens to the mRNA – whether it is broken down or locked in a dormant form. miRNA binds to certain mRNA like an inferior strip of Velcro. The researchers’ hypothesis is that the miRNA-mRNA bond is controlled by structural principles and not just by the sequence complementarity, as is currently believed. They also think that the miRNA structure is fluid and can adapt to different environments, like an extra control mechanism for finding the right mRNA. Since the miRNA structure needs to be physically manipulated and its role in the brain assayed, it has not been possible to test this hypothesis. However, with the new methods they have developed, the researchers are uniquely placed to find the answer to one of the biggest conundrums in biology: how are the functions of RNA regulated in a living organism? “In collaboration with Emma Andersson, who is a developmental biologist here at KI, and together with two external experts in synthetic organic chemistry and molecular modelling, we can now discover and define if and how the structure of a miRNA controls function", says Dr Petzold. “We’ll be analysing the role of a specific miRNA in brain development and are using miR-34a for its well-studied ‘targetome’. We already know which mRNA it attaches to, but not what happens then, or why.” She continues: “This multidisciplinary project will produce revolutionary tools for analysing and identifying important interactions that regulate miRNA biology in living organisms with atomic resolution.” Regulation of mammalian mtDNA gene expression Project: Regulation of mammalian mtDNA gene expression Grant awarded: SEK 47,000,000 over five years Principal applicant: Professor Nils-Göran Larsson, Department of Medical Biochemistry and Biophysics Our bodies contain a large number of specialised cell types that need constant access to energy in order to perform a wide range of functions. The mitochondria are often referred to as the cell’s power plants since they convert the energy from food to the energy-rich substance ATP. Mitochondrial regulation is essential to the normal functioning of our cells: to ability of the neurons of the brain to transmit signals, for example, or the myocardial cells’ ability to contract and pump the blood through our arteries. The failure of the mitochondria to produce energy is the cause of many hereditary diseases that attack the human nerve system, muscles, heart and other organs. Reduced mitochondrial function is also thought to play an important part in the pathogenesis of different types of age-related disease, such as diabetes and Parkinson’s, as well as in the ageing process itself. The research programme led by Professor Nils-Göran Larsson describes a number of basic scientific experiments designed to better understand how the mitochondria regulate the expression of their own DNA (mtDNA) and thus the cell’s energy supply. Even though mtDNA is relatively tiny and only codes for 13 proteins, without it, the cell’s energy supply would not function. Several hundred genes in the cell nucleus code for proteins that are imported into the mitochondria to regulate the expression of mtDNA, a process that is therefore extremely complex and appears to take place on many levels. “In our research programme we’ll be carrying out a series of advanced experiments to identify different mechanisms that control mtDNA and its expression,” says Professor Larsson. “Understanding more about how mtDNA expression is regulated will help us understand how the energy supply is controlled during different physiological processes and study disease processes and ageing.” Characterization, Surveillance and Targeting of Cancer Stem Cells Project: Characterization, Surveillance and Targeting of Cancer Stem Cells Grant awarded: SEK 45,250,000 over five years Principal applicant: Professor Sten Eirik W. Jacobsen, Center for Haematology and Regenerative Medicine, Department of Medicine, Huddinge; Department of Cell and Molecular Biology, Karolinska Institutet, and Haematologic Centre, Karolinska University Hospital Co-applicants: Senior researcher Yenan Bryceson, Professor Eva Hellström-Lindberg, Professor Seishi Ogawa and Assistant Professor Petter Woll Cancer relapse after an initially successful treatment is still a major problem and the toughest challenge for modern cancer therapies. Such late relapses are thought to be caused by the existence of rare cancer stem cells, which, in being demonstrably resistant to treatment and capable of forming new tumours, play an important part in the onset and development of the disease. It is therefore imperative that they are the target of all future cancer therapies. Myelodysplastic syndrome (MDS) is a form of blood cancer deriving from the stem cells in the bone marrow, and leads to a lack of mature blood cells in the circulatory system. For many patients, the disease intensifies over time and can turn into acute leukaemia with a worse prognosis. The researchers behind this project have recently identified the cancer stem cells in MDS as well as several significant genetic mutations in. The grant from KAW will allow Professor Sten Eirik W. Jacobsen, who received the 2014 Tobias Prize along with a grant from the Tobias Foundation for his work on MDS, and four other leading research groups at Karolinska Institutet’s new Centre for Haematology and Regenerative Medicine (HERM), to address several important biological and clinical aspects of MDS. These include the biology behind MDS induced anaemia, the MDS transformation tendency into acute leukemia, the development of immunotherapy, and the significance of recently discovered mutations in MDS. “Our joint objective is to get a better understanding of the disease MDS both in terms of disease mechanisms, stem cell biology, immunology, and the molecular mechanisms behind MDS. We will conduct studies in animal models as well as in patients.  By combining our respective expertise in the five research groups, we hope to develop therapies that more specifically and effectively can eliminate the MDS stem cells, but also through other approaches give rise to more lasting therapeutic results and remedies for MDS,” says Professor Jacobsen. Even though the cancer stem cells in other blood cancers and tumours will probably differ significantly from the MDS stem cells, the researchers hope to glean from these studies a better understanding of cancer stem cells and of the development of cancer stem-cell therapies for cancer more generally.”

In the 1990s, Yoshinori Ohsumi described how our cells keep their house in order. Now that he has been awarded a Nobel Prize for his discoveries, the research field has exploded – cellular waste management has proved to be critical to cancer and many other diseases. “The 2016 Nobel Prize in Physiology or Medicine goes to Yoshinori Ohsumi for his discoveries concerning the mechanisms of autophagy, a fundamental process for the breakdown and recycling of cell components,” announced Nobel Committee secretary Thomas Perlmann at Monday’s press conference. Afterwards, committee member Nils-Göran Larsson explained: “Just like an apartment, our cells gather junk,” he says. “Things get worn out and broken and need replacing. Yoshinori Ohsumi has described the fundamental mechanisms for how cells go about cleaning up and recycling.” And this is not a matter of simple touching up, but of a constant renovation process in which the body’s building blocks are broken down and recycled.  “A person weighing 60 kilos contains about nine kilos of proteins,” says Professor Larsson. “Two or three hectograms of these proteins are replaced every day through these processes.” Famine in the cell The word autophagy comes from the Greek and means “self-eating”. It denotes a special method of cleaning up, in which the cell’s contents are enclosed by membranes to form vesicles that are then transported to lysosomes, which act as a kind of recycling station for the decomposition of biological material. Yoshinori Ohsumi, professor at Tokyo Institute of Technology, was the first to describe in detail how this occurs. During the early 1990s he managed to identify, through a series of experiments on common baker’s yeast, genes that regulate autophagy. He then went on to explain the function of the proteins involved and showed that human cells use the same machinery. “At first he was rather alone in the field,” says Professor Larsson. “But he carried on working and produced some thorough, high quality studies. He is a very meticulous researcher.” It is now known that autophagy gives rapid access to energy in the absence of sufficient nutrients and makes sure that the effects of both this and invading viruses can be neutralised. The mechanism has also turned out to be involved in different diseases, such as cancer, diabetes, Parkinson’s disease and dementia of various kinds. Autophagy research has gradually expanded, only to completely explode in recent years judging by the sharp rise in the number of papers published on the subject. Involved in many diseases “I guess the reason that scientists have become more interested in the research field recently is that more and more have realised its involvement in different diseases,” says Helin Norberg, cancer researcher at the Department of Physiology and Pharmacology and one of the many scientists following in Professor Ohsumi’s footsteps. Cancer cells develop internal damage and are subjected to different kinds of stress caused by the lack of oxygen and nutrients. They then protect themselves from such stress by increasing their internal recycling activity and quickly metabolising the energy they need. In this respect, autophagy is an unwanted phenomenon as it helps the cancer cells to survive. Dr Norberg is attempting to find ways of regulating autophagy to the cancer cell’s disadvantage. Her aim is selective autophagy, whereby only certain essential proteins that promote tumour development are destroyed.   Several clinical trials are under way with substances that affect autophagy, and while there is, as yet, no marketable therapy available, Dr Norberg hopes that her own research will one day result in a new breed of cancer drug. “I’m so happy today, this is important recognition for the entire field and shows that it has vital future relevance. I also hope that it will help researchers in other fields find new links to diseases,” says Dr Norberg. Important process in neurodegenerative diseases Caroline Graff, professor of genetic dementia research at the Department of Neurobiology, Care Sciences and Society, describes a similar trend for autophagy research in her own field. “Autophagy is a fascinating and important process in neurodegenerative diseases, which are characterised, as you might know, by the accumulation of misfolded proteins in the brain and nerve system,” she says. “For some reason these protein clusters aren’t cleared away but remain in place to interfere with cellular function.” However, it is only in recent years that really strong evidence has been forthcoming: “We now know that some genes that are mutated in patients with hereditary forms of dementia are the same genes that are needed for autophagy to work,” she says. “We’ve suspected this for a long time, but we’ve not seen this very clear connection before.” Neurodegenerative diseases like Alzheimer’s, ALS and frontal lobe dementia differ in terms of the types of protein that accumulate in the nerve cells. While there is currently no effective treatment for any of these diseases, Professor Graff sees autophagy as a light at the end of their common tunnel.  “If we can learn to help autophagy get started so that the cells become increasingly better at cleaning away misfolded proteins, I think there’s hope that we’ll be able to develop treatments for many of these diseases,” she says. Dr Norberg maintains that her research would not have been possible without Professor Ohsumi. “He discovered the fundamental processes, which others have then built upon. We’d never have got this far without his discoveries,” she says. Text: Ola Danielsson

(This is the press release from Nature Neuroscience) Very rare genetic mutations that disrupt the function of genes are common in patients with schizophrenia and are also associated with fewer months of formal education in healthy individuals, report two independent papers published online this week in Nature Neuroscience. However, since many cognitive, personality and psychological factors also influence educational attainment, it is unknown which of these are affected by this collection of mutations. Genetic changes that are common in the population contribute to variation in traits such as cognitive function and also risk for psychiatric disorders such as schizophrenia. Damaging genetic changes have been made rare through natural selection, which makes it more difficult to assess their contribution to disease. To investigate the impact of rare damaging mutations, Steven McCarroll, Giulio Genovese and colleagues and Andrea Ganna and colleagues examined the protein coding sequences of DNA (or exomes) in thousands of unrelated individuals, some of who have been diagnosed with schizophrenia. McCarroll and Genovese’s group focused on mutations that were observed only once in their sample of 12,332 Swedish individuals and never in a large collection of over 45,000 exomes of individuals without psychiatric disorders. They found that rare damaging mutations were more common in patients in schizophrenia overall and that the affected genes were expressed specifically in the synapses of brain cells and not in other cell types or organs. Ganna’s group assessed the relationship between rare damaging mutations (observed once in their sample and never in over 65,000 exomes) and years of educational attainment among 14,133 individuals from Sweden, Estonia and Finland. They focused on a set of genes that are very sensitive to changes in their DNA and do not have many mutations in the general population. Each damaging mutation in one of these genes was associated with 3 less months of education. When the authors looked at those genes expressed in the brain, then the impact of one of these mutations increased to 6 months fewer of education. Although the authors investigated thousands of individuals, their sample sizes are still too small to implicate any one gene with a rare mutation contributing to schizophrenia or less education. Larger studies are needed to pinpoint specific genes and specific brain processes as well as to assess the overlap between rare genetic risk for psychiatric disease and typical variation in cognitive function. A.G. is supported by the Knut and Alice Wallenberg Foundation (2015.0327) and the Swedish Research Council (2016-00250). M.G.N. is supported by the Royal Netherlands Academy of Science Professor Award (PAH/6635) to Dorret I. Boomsma. V.S. was supported by the Finnish Foundation for Cardiovascular Research. This study was supported by grants from the National Human Genome Research Institute (U54 HG003067 and R01 HG006855); the National Institute of Mental Health (1U01MH105666-01 and 1R01MH101244-02); the National Institute of Diabetes and Digestive and Kidney Disease (1U54DK105566-02); the Stanley Center for Psychiatric Research; the Alexander and Margaret Stewart Trust; the National Institutes of Mental Health (R01 MH077139 and RC2 MH089905); the Sylvan C. Herman Foundation; EU H2020 grants 692145, 676550 and 654248; Estonian Research Council Grant IUT20-60, NIASC, EIT–Health; NIH-BMI Grant No. 2R01DK075787-06A1; and by the EU through the European Regional Development Fund (Project No. 2014-2020.4.01.15-0012 GENTRANSMED). Publication Neuroscience: Ultra-rare disruptive and damaging mutations influence educational attainment in the general population  Andrea Ganna, Giulio Genovese, Daniel P Howrigan, Andrea Byrnes, Mitja I Kurki, Seyedeh M Zekavat, Christopher W Whelan, Mart Kals, Michel G Nivard, Alex Bloemendal, Jonathan M Bloom, Jacqueline I Goldstein, Timothy Poterba, Cotton Seed, Robert E Handsaker, Pradeep Natarajan, Reedik Mägi, Diane Gage, Elise B Robinson, Andres Metspalu, Veikko Salomaa, Jaana Suvisaari, Shaun M Purcell, Pamela Sklar, Sekar Kathiresan, Mark J Daly, Steven A McCarroll, Patrick F Sullivan, Aarno Palotie, Tõnu Esko, Christina M Hultman &Benjamin M Neale Nature Neuroscience, Published online 03 October 2016 doi:10.1038/nn.4404, and doi:10.1038/nn.4402

Young adult self-harmers run a higher risk of also committing suicide, a new study from Karolinska Institutet published in the journal Psychological Medicine reports. The risk of suicide is 16 times higher in people who have been treated for self-harming behaviour than in their peers. The current study concerns self-harming in young people and how it impacts on the risk of mental illness or suicide later in life. While self-harm is relatively common, particularly amongst the young, not very much is known about what becomes of these individuals later in life. The aim of the study was to see if self-harming at a young age is an expression of a temporary crisis or of a more chronic mental problem. “We also wanted to find out if the risk of suicide increases and who is at the greatest risk of mental illness and suicide,” says lead author Karin Beckman, specialist in psychiatry and doctoral student at the Department of Clinical Neuroscience. The study involved 13,731 individuals between the ages of 18 and 24 who had been treated for self-harm between 1990 and 2003, along with 137,310 who had not[NB1] . The average follow-up time was 12.2 years after treatment and 62.3 per cent of the participants were female. All individuals who were hospitalised for self-harm for the first time in Sweden during this period were included in the study, which used anonymised information from six Swedish registries, including the Swedish National Patient Register and the Swedish Prescribed Drug Register. The study showed that the risk of suicide is 16 times higher in young adults who had been hospitalised in connection with self-harm than in their peers. The researchers also observed that many of them had persistent psychiatric problems: a follow-up five years after the self-harm episode revealed that one in five were receiving in-patient psychiatric care and half were being treated with psychiatric drugs. Having a mental illness, particularly a psychosis, before or in connection with self-harm increased the risk of problems later in life as regards both suicide and psychiatric ill-health. “Our results show that we have to focus more on young adults who self-harm if we’re to reduce the risk of their developing psychiatric issues as adults and of suicide,” says Dr Beckman. “Doctors dealing with self-harm should also carefully assess and deal with any mental illnesses, since they have significant consequences for later negative prognoses.” She continues: “We still know regrettably little about what happens to individuals who self-harm but who remain under healthcare service radar. We also have to learn more about what makes many early self-harmers cope well in the future and about what intervention best helps them.”  The study was financed with grants from the Swedish Council for Working Life and Social Research (FAS), the Bror Gadelius Memorial Fund and the Swedish Research Council. Publication “Mental illness and suicide after self-harm among young adults- long-term follow-up of self-harm patients, admitted to hospital care, in a national cohort” Karin Beckman, Ellenor Mittendorfer-Rutz, Paul Lichtenstein, Henrik Larsson, Catarina Almqvist, Bo Runeson, Marie Dahlin. Psychological Medicine, published online 20 September, 2016, doi:http://dx.doi.org/10.1017/S0033291716002282

The skin is the largest organ in mammals and it serves to protect the body from outside influences, such as physical damage, radiation, fluid loss or extreme temperatures. To fulfill this function, a plethora of cell types with diverse functions and molecular identities has to work in concert. However, it is still unclear how many different cell populations can actually be found in the epidermis and the hair follicles, and what exactly makes one cell different from another. In a new study from Karolinska Institutet, researchers provide an in-depth analysis revealing 25 epidermal cell populations that, surprisingly, can be explained almost fully by just two biological parameters - the differentiation status of the cell and the niche in which the cell is located. The study, a collaboration between the labs of Maria Kasper and Sten Linnarsson, used single-cell RNA-sequencing to analyze the gene expression of more than a thousand individual cells from adult mouse skin. With this method they were able to link each cell to a specific molecular identity and to cluster them accordingly. Analyzing the gene expression signatures associated with each of these cell populations revealed putative functional roles for each population and made it possible to search for shared patterns of gene expression between different populations. These new insights into the organization of the epidermis have profound influence on the understanding of how the skin functions. “Overall, we were able to find 25 cell populations with distinct molecular identities and functional roles in the murine epidermis and the hair follicle, many of which have not been described before. What was most intriguing was that, despite this high number of different populations and identities, most variety of the cells could be explained by only two parameters – time and space,” says the study’s first author Simon Joost. The time parameter would correspond to the differentiation status of the cells – whether they are young and dividing cells in the basal layer, or functionally mature cells in the outer layers. Space would correspond to the niche that the cell is located in – whether they are located in the interfollicular epidermis (the part of the skin that is not hair follicle) where they form the skin barrier, or whether they are located in one of the many compartments of the hair follicle where they grow and maintain the hair. Furthermore, the study leader Maria Kasper explains, “A vast number of tissue stem cell populations with different gene expression profiles and diverse localizations have been described in the epidermis in recent years. However, our data show that, while the expression profiles of the different populations indeed vary according to their locations, the gene expression linked to their stem cell identity is surprisingly similar across these locations”. These findings challenge previous paradigms of skin maintenance. Understanding the identity and interplay of different cell populations in the healthy skin will enable researchers to better understand the specific changes occurring in skin stem cells, for example when they contribute to wound healing or when they undergo transformation to give rise to a tumor. Thus, this cell map of healthy skin will also benefit future studies on damaged as well as diseased skin. Publication Single-Cell Transcriptomics Reveals that Differentiation and Spatial Signatures Shape Epidermal and Hair Follicle Heterogeneity Simon Joost, Amit Zeisel, Tina Jacob, Xiaoyan Sun, Gioele La Manno, Peter Lönnerberg, Sten Linnarsson, and Maria Kasper Cell Systems, published online 14 September 2016, in print 28 September 2016 , doi: 10.1016/j.cels.2016.08.010   

The Nobel Assembly at Karolinska Institutet has today decided to award the 2016 Nobel Prize in Physiology or Medicine to Yoshinori Ohsumi for his discoveries of mechanisms for autophagy. This year's Nobel Laureate discovered and elucidated mechanisms underlying autophagy, a fundamental process for degrading and recycling cellular components.   The word autophagy originates from the Greek words auto-, meaning ”self”, and phagein, meaning ”to eat”. Thus, autophagy denotes ”self eating”. This concept emerged during the 1960's, when researchers first observed that the cell could destroy its own contents by enclosing it in membranes, forming sack-like vesicles that were transported to a recycling compartment, called the lysosome, for degradation. Difficulties in studying the phenomenon meant that little was known until, in a series of brilliant experiments in the early 1990's, Yoshinori Ohsumi used baker's yeast to identify genes essential for autophagy. He then went on to elucidate the underlying mechanisms for autophagy in yeast and showed that similar sophisticated machinery is used in our cells. Ohsumi's discoveries led to a new paradigm in our understanding of how the cell recycles its content. His discoveries opened the path to understanding the fundamental importance of autophagy in many physiological processes, such as in the adaptation to starvation or response to infection. Mutations in autophagy genes can cause disease, and the autophagic process is involved in several conditions including cancer and neurological disease. Yoshinori Ohsumi was born 1945 in Fukuoka, Japan. He received a Ph.D. from University of Tokyo in 1974. After spending three years at Rockefeller University, New York, USA, he returned to the University of Tokyo where he established his research group in 1988. He is since 2009 a professor at the Tokyo Institute of Technology.

Alexey Amunts is the recipient of the 2016 Lennart Nilsson Award for his pioneering work in the ongoing “Resolution Revolution”, using cryoelectron microscopy (cryo-EM) to visualize structures of individual proteins. Alexey Amunts is head of the Swedish cryo-EM laboratory at SciLifeLab and researcher in the Department of Biochemistry and Biophysics at Stockholm University. Cryo-EM led him and his team to the first visualizations of a protein complex that regulates a cell’s energy budget, the mitoribosome, with extremely high resolution – at the atomic scale. The method uses a highly focused electron beam to shoot electrons at biological samples, for example mitoribosomes, frozen in liquid nitrogen, at about –200°C. Hundreds of thousands of pictures of a single mitoribosome are combined with the help of computational analysis, and the final result is an extremely detailed three-dimensional model of the original biological structure. These visualisations provide essential information about structures that govern cellular functions and modes of action. Amunts has spent many years trying to determine the structures of biological molecular complexes, a path on which he started as a PhD student in Israel. While he’d first intended to go to medical school, his path changed when he discovered an interdisciplinary research program at Tel Aviv University. He had his first foray into visualising large molecules or “macromolecules,” looking at a “macromolecular machine” in plants that converts sunlight into energy, photosystem I. Amunts and his mentor, Nathan Nelson, used X-ray crystallography to visualise this macromolecule – the most powerful tool available at the time. Meanwhile, cryo-EM methods were on the horizon. Amunts moved for his postdoc to the MRC Laboratory of Molecular Biology in Cambridge UK, where the technique has been evolving. In 2014, he, his supervisor Venkatraman Ramakrishnan (recipient of the Nobel Prize in Chemistry, 2009) together with colleagues Sjors Scheres and Alan Brown were among the first to prove the method could capture such detailed and fine-scaled images of a biological structure, using the mitoribosome as their subject. Since then, Amunts and his research team have created images of structural features of the mitoribosome that orchestrate the metabolism of cancer cells. The mitoribosome could be a kind of Achilles’ heel for tumors, and a target for therapy. Amunts and his team have gone further with cryo-EM to show the mitoribosome bound to potentially novel therapeutic compounds. They captured the first high-resolution images of a drug bound to mitoribosome, which opens up promising perspectives for structure-based drug design using cryo-EM. Earlier this year Amunts became director of the Swedish cryo-EM facility, where he hopes to contribute to that work. “Today, our lab helps Swedish the research community by providing them with new cryo-EM methods, while scientists from all over the country feed us with ever more complicated problems that require extra tailoring. That’s how we progress, and the research environment in Sweden benefits.” Expanding the promising and continually developing method also presents new challenges, for example, crunching terabytes’ worth of image data that must be analysed quickly and effectively. Amunts is excited and amazed at the potential on the horizon for the new technique: “A new student came to our lab with no prior cryo-EM experience,” he recalls. “Within 10 months she cracked a problem that could not be solved for 10 years by generations of more experienced postdocs from better funded labs. So imagine what an era of scientific progress and enrichment we are stepping into.” Text: Naomi Lubick

Jiri Lukas and Jiri Bartek (to the right). Photo credit: Kennet Ruona Jiri Bartek, professor at Karolinska Institutet’s Department of Medical Biochemistry and Biophysics and SciLifeLab in Stockholm, and Jiri Lukas, professor at the Novo Nordisk Foundation Centre for Protein Research at Copenhagen University, have been awarded the Fernström Foundation’s Grand Nordic Prize for their research on cellular responses to DNA damage. Every year, the Eric K. Fernström Foundation awards local prizes to researchers at Sweden’s six medical faculties, and a Grand Nordic Prize of one million kronor. This latter prize is shared this year by professors Jiri Bartek and Jiri Lukas. View this press release from Lund University to find out more.

Researchers at Karolinska Institutet and Ludwig Institute for Cancer Research have characterized how and to what degree our cells utilize the gene copies inherited from our mother and father differently. At a basic level this helps to explain why identical twins can appear rather different, even though they share identical genetic makeup. With this knowledge we will better understand the variation in outcomes of genetic disorders. Humans have two copies of all autosomal genes, one inherited from the mother and one from the father, and often the two copies are not perfectly identical due to small differences in their DNA sequence. Therefore, variation in the utilization of the two copies in cells has functional consequences, but the nature and patterns of their gene copy utilization has remained largely unknown. Now, the researchers have provided answers to this longstanding question in molecular genetics. They used allele-sensitive gene expression analyses, so called “single-cell RNA-sequencing”, on the newly divided cells to characterize the dynamics of gene copy expression in mouse and human cells in remarkable detail. “Our experiments allowed us to determine which genes get locked into expressing only one gene copy and which genes that dynamically switches between the two gene copies over time”, says Björn Reinius, at the Department of Cell and Molecular Biology one of the lead authors of the study published in the journal Nature Genetics. Non-identical genetic In genetics, the two gene copies are referred to as the two “alleles” of each gene. Indeed, DNA differences in the mother’s and father’s genomes explain why siblings can appear physiologically rather different from each other, as the siblings inherit different sets of alleles and thereby have non-identical genetic makeup. However, even between so-called identical twins, which carry precisely the same set of alleles, there are still differences in manifestation of some genetic traits. For example, sometimes only one of two twins suffers the effects of a genetic disorder – even though both twins carry the same disease allele. Historically this was mainly explained by variations in external environment and life history. However, since the last few decades we know that purely random molecular events taking place inside the cells can actually affect how and when the set of alleles are expressed. The mother’s allele of a certain gene may be expressed in some of the individual’s cells while the father’s allele is expressed in other cells of the very same individual. Whether this “choice” of expressed allele tends to be forwarded through cell division or whether the allelic choice takes place independently in each cell again and again over time has remained unknown. Patterns flicker These competing scenarios would result in crucially different physiological outcomes; since the first results in patches of cells in the body having the same set of expressed alleles, while the other scenario results in allelic expression patterns that “flicker” between the mother’s and father’s gene copies over the coarse time. The results of the present study, demonstrate that most autosomal genes dynamically fluctuate in expression of the two alleles, while only as little as 0.5–1% of genes are fixed into expressing only one. "The knowledge gained from this detailed study on the nature of gene transcription will help researchers and medical doctors to better understand and model the mechanisms underlying variable outcomes in genetic disease”, says Rickard Sandberg, at the Department of Cell and Molecular Biology at Karolinska Institutet and the Ludwig Centre for Cancer Research, who supervised the project. The research was supported by the Swedish Research Council, the European Research Council, the Swedish Foundation for Strategic Research, the Swedish Cancer Society, Tobias Stiftelsen, Strategic research area StratRegen, Knut & Alice Wallenberg Foundation, and the Torsten Söderberg Foundation Publication Analysis of allelic expression patterns in clonal somatic cells by single-cell RNA-seq, Björn Reinius, Jeff E. Mold, Daniel Ramsköld, Qiaolin Deng, Per Johnsson, Jakob Michaëlsson, Jonas Frisén and Rickard Sandberg, Nature Genetics, 26 October 2016, doi:10.1038/ng.3678

The Grand Silver Medal 2016 from Karolinska Institutet is awarded to Anders Ekbom, Ingemar Ernberg, Agneta Nordberg, Bengt Norrving and Elisabeth Olsson in special recognition of the outstanding contributions they have made to medical research and Karolinska Institutet. Anders Ekbom, Senior Professor of Epidemiology at the Department of Medicine, Solna, has been awarded the Grand Silver Medal for his exceptional work within several fields of research and his significant contributions to the whole of Karolinska Institutet. Professor Ekbom has played a major part in developing cooperation between KI and Karolinska University Hospital. He started the epidemiological research school for clinicians, creating increased exchanges between clinical operations and research at KI and paving the way for many clinicians to start carrying out research. During the early 2000s, he built up the highly successful Unit for Clinical Epidemiology at the Department of Medicine, Solna. In recent years, he has been a key figure in the introduction of research at the New Karolinska Hospital. Professor Ekbom has been highly active and successful within a number of fields of research, and now has more than 500 publications to his name. For example, his research has been of great significance to the way in which patients with ulcerative colitis, Crohn’s disease and rheumatoid arthritis are monitored and treated.                                                                                                    Ingemar Ernberg, Senior Professor of Tumour Biology at the Department of Microbiology, Tumor and Cell Biology (MTC), has been awarded the Grand Silver Medal for his invaluable efforts to strengthen and develop the university’s operations. During his nearly 50 years at KI, Professor Ernberg has served as chairman and member of many decision-making and advisory boards and committees at the university. As Head of Department of MTC, he has been a shining example of creative leadership, and has built up a research and development environment that has become a role model for other departments at KI. He has taken the initiative for new research programmes, for example “What is Life?” and “Culture and Brain”, participated in several national organisations and initiative groups, and been extremely active in international contexts. His work has strengthened KI as a university and as a global player, and he has forged many rewarding partnerships. Professor Ernberg has also worked for increased adult education and information dissemination, including through pedagogical collaborative projects with schools, writing scientific literature and popular science books, and taking part in a number of TV and radio programmes. Alongside this, Professor Ernberg has also carried out his own research of the highest international quality, focusing primarily on the EBV virus – how infections and other mechanisms lead to the development of cancer in humans. Agneta Nordberg, Professor of Clinical Neuroscience at the Department of Neurobiology, Care Sciences and Society, has been awarded the Grand Silver Medal for her extraordinary efforts for patients with dementia. She has taken on the great challenges of Alzheimer’s research with tireless energy, contributing towards improved diagnosis and treatment opportunities for these patients. She is a world leader within the field of early diagnosis of dementia, and studies processes in the brain with PET scans. She has won international recognition for this pioneering research, and PET imaging is now approaching clinical implementation. Professor Nordberg has published more than 450 scientific articles, and has received many awards over the years. She leads a successful research team, and has benefited KI greatly through her involvement as a member of several boards and foundations, among them the Nobel Assembly. She is also a skilled clinician, focusing particularly on patients with early memory impairment. Here, she shows great commitment to her patients and is passionate about ensuring that they get the best possible diagnosis and treatment. Bengt Norrving, former university director and administrative director at KI, has been awarded the Grand Silver Medal for his outstanding contributions to the university. Bengt Norrving was vice-chancellor of the University of Health Sciences before it was incorporated into KI in 1998. He was actively involved in the pre-merger talks and helped to make sure the UHS was fully integrated into the KI organisation. Bengt Norrving’s wide experience of the public sector, academia, the departmental sphere and the municipal sector enabled him to bridge in exemplary fashion the cultural differences that existed between the two institutions. On behalf of the Ministry of Education and Research he has, amongst other commissions, led the national ALF (the agreements on medical education and research) negotiations on two occasions.  His unique knowledge of the ALF agreement has been vital to the successful collaboration that has existed between KI and Stockholm County Council for many years. During his years at KI, Bengt Norrving was a highly competent and proactive official, and his influence on the development of the university’s core activities remained extremely significant until his retirement in 2014. Elisabeth Olsson, Professor Emerita of Physiotherapy at the Department of Neurobiology, Care Sciences and Society, has been awarded the Grand Silver Medal for her unparalleled efforts within research and education at Karolinska Institutet. She is regarded as a pioneer within physiotherapy. For eight years (1993-2001) she was Head of Department at the former Department of Physiotherapy at KI, and was subsequently Section Manager and Deputy Head of Department at the former Neurotec department (until 2005). During this period, she helped to develop the subject of physiotherapy, and the field underwent dramatic academic growth. Professor Olsson implemented a three-year bachelor’s level programme and a one-year master’s programme in physiotherapy.  She also created different conditions for research in the area and successfully established combined senior lectureships for physiotherapists together with Sweden's first professorship in physiotherapy. The number of physiotherapists with third-cycle education grew significantly, and the profession began to be engaged within central administrative functions at all levels. Professor Olsson has been involved not only in educational issues and on boards and programme committees, among others as representative of the teaching staff on the university board, but also as a representative of the university as an expert for many external inquiries and committees. In recent years she has successfully resumed her own research within motion analysis now focusing on new training and evaluation techniques for the elderly, and this project will now continue following Professor Olsson’s retirement.