scilifelab stockholm 2012

Annual report 2012Science for Life Laboratory Stockholm

2 | 2012 Annual report SciLifeLab Stockholm

SciLifeLab Stockholm Annual report 2012 | 1

Science for Life Laboratory Stockholm

Annual report 2012

Acini of the mammary gland of normal human breast with OmniFluorBright (OFB) staining.


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SciLifeLab in brief

SciLifeLab’s vision is to be an internationally leading center in large-scale life science research. With the motto Health and Environment the research supported and performed is spanning a broad field, aiming not only for deeper knowledge about human diseases, improved health care, development of diagnostic tools and potential drugs, but also for mapping of microbial activities in sensitive ecosys-tems, engineering for biofuel production and plant biotechnology.

SciLifeLab develops and provides access to ad-vanced instrumentation and technical expertise in large-scale molecular biosciences. The objective is to enable Swedish researchers to carry out extensive and comprehensive analysis of genes, transcripts and proteins in humans, plants and relevant microbes, such as viruses and bacteria, and to cast light on the complex interplay between different

molecular components in living cells, tissues and organs related to human diseases or environmental issues. In order to interpret the massive amount of data produced in many large-scale analyses, expertise in bioinformatics and systems biology is essential and prioritized areas at SciLifeLab.

By combining a “tool box” of advanced instrumen-tation and expertise from a wide range of life science areas, interdisciplinary research involving high-throughput DNA sequencing, analysis of gene expression, protein profiling, cellular profiling, advanced bioinformatics, biostatistics and systems biology, is carried out.

The two nodes in Stockholm and Uppsala will in the middle of 2013 merge into one organization. This report describes the activities of SciLifeLab Stockholm during 2012.

Over the past three years, Science for Life Laboratory (SciLifeLab) has been built up

in Stockholm and Uppsala to serve as a national infrastructure for high-throughput

and technically advanced research in the life sciences, and to provide an attractive

research environment for top-level research groups. SciLifeLab was established in

2010, with support from the Swedish government. It is a collaboration between the

Royal Institute of Technology (KTH), Karolinska Institutet (KI), Stockholm University

(SU) and Uppsala University (UU).


Table of contents

SciLifeLab in brief . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

SciLifeLab Stockholm 2012 . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

Highlights of 2012 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

SciLifeLab in constant progress . . . . . . . . . . . . . . . . . . . . . . . . 8

The organization of SciLifeLab Stockholm 2012 . . . . . . . . . . 9

The platforms offer technology infrastructure

and competence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10

Highlights from research

The Subcellular Protein Atlas . . . . . . . . . . . . . . . . . . . . . . . . . 13

Targeting DNA repair to find novel

anti-cancer treatments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14

Membrane protein biogenesis . . . . . . . . . . . . . . . . . . . . . . . . 15

Reading the genome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16

Na,K-ATPase – an overlooked protein in the brain . . . . . . . 17

Spatial transcriptomics of the brain . . . . . . . . . . . . . . . . . . . . 18

Understanding the molecular basis

of nerve signals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20

Bioinformatics for network and systems biology . . . . . . . . 22

Collaboration with industry . . . . . . . . . . . . . . . . . . . . . . . . . . 23

The SciLifeLab Stockholm researchers . . . . . . . . . . . . . . . . . 24

SciLifeLab Stockholm – Scientific publications . . . . . . . . . . . 26

The Platform Facilities

Genomics Experimental . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28

Genomics Bioinformatics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29

Cell Profiling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31

Biobank Profiling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32

Cell Screening . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33

Advanced Proteomics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34

Clinical Proteomics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35

Tissue Profiling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36

Chemical Biology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38

Protein Production . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39

Advanced Light Microscopy (ALM) . . . . . . . . . . . . . . . . . . . . 41

Karolinska High Throughput Center (KHTC) . . . . . . . . . . . . 42

Bioinformatics Infrastructure for Life Sciences (BILS) . . . . . 43

The Wallenberg Advanced Bioinformatics

Infrastructure (WABI) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44

Management of SciLifeLab Stockholm . . . . . . . . . . . . . . . . . 46


SciLifeLab Stockholm 2012

The development of SciLifeLab Stockholm has continued at a rapid pace during 2012 and the year has been scientifically productive. The center has noticed an increased interest from researchers to use the state-of-the-art technologies provided by the platform facilities. Hundreds of collaborative and service projects have been completed with users from all major universities in Sweden. To further broaden the resources available, three new platform facilities have been established. The center has also expanded with an additional 170 researchers, reaching 350 persons at the end of 2012. These include almost 40 senior research leaders performing research in a wide range of molecular bioscience areas. SciLifeLab Stockholm will continue to expand during 2013 when an adjacent building will be inaugurated, then encompassing more than 600 researchers and 14,000m2 of space for the technical infrastructure and research within large-scale life science.

Substantial external funding has enabled investments in new instrumentation and recruitment of personnel to several platform facilities. Through generous grants from the Knut and Alice Wallenberg Founda-tion the Genomics facility has been able to triple the sequence capacity during the year and an infrastruc-ture for in-depth bioinformatics support has been established. This kind of support is an important key for success in on-going large-scale studies.

The strengthened research environment is illustrated by the considerable increase in number of publica-tions produced by SciLifeLab Stockholm researchers over the year. During 2012 one article per week has been published in high impact journals such as Nature, Science and PNAS. Read more about some of the research highlights at SciLifeLab Stockholm on page 12 to 22. Several patents have also been filed, and there are lively collaborations with industry on different levels.

In 2012, the Swedish government decided on addi-tional funding to SciLifeLab, with the mission to unify the Stockholm and Uppsala nodes and become an infrastructure with a national responsibility. SciLifeLab will provide large-scale state-of-the-art instrumentation and technical know-how, including in-depth bioinformatics support, to all Swedish researchers in order to strengthen multidisciplinary research throughout the nation.

The year of 2012 has been an exciting and

rewarding year for SciLifeLab Stockholm.

Development of SciLifeLab Stockholm from the start in 2010. The center has expanded with new Platform Facilities and research groups each year. In 2013 the nodes in Stockholm and Uppsala will merge into one organization and become a national infrastructure for large-scale biosciences.


• Several new bioinformatics algorithms were developed

and published, including FunCoup 2 .0 and BOCTOPUS

• Novel methods for quantitative proteomics using mass

spectrometry were developed

• A step towards more efficient spruce breeding programs

was taken by using the next generation sequencing

facility at SciLifeLab coupled with advanced bioinformatics

and molecular biology methods

• Dramatic resistance to colorectal cancer formation was

confirmed in mouse models

• An additional 4000 m2 of space was inaugurated and

another 170 researchers moved in to reach a total of 350

persons

For details regarding some of the scientific highlights, please go to pages 12 to 22.

• The Swedish government announced increased funding to

SciLifeLab and the start of a new organization in 2013

• The Knut and Alice Wallenberg Foundation awarded

grants to strengthen the Genomics facility and to start up

the Wallenberg Advanced Bioinformatics Infrastructure

(WABI)

• Three new platform facilities were established; Advanced

proteomics, Chemical biology and Protein production

• AstraZeneca started up the Translational Science Centre

at SciLifeLab Stockholm and announced a first round of

funding for research projects

• The Human Protein Atlas announced in September 2012

the mapping of 70% of the human protein-coding genes

• Three SciLifeLab Stockholm researchers were awarded 53

MSEK from the Knut and Alice Wallenberg Foundation for

research about viruses and bacteria, the brain and its

diseases and for understanding and developing new

cancer drugs . Two of its Center Directors (von Heijne and

Uhlen) received Wallenberg Scholar Awards

Highlights of 2012

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Here follows some examples of organizational

and scientific highlights during the year.


SciLifeLab in constant progress

From 2013 SciLifeLab will receive substantially increased funding from the Swedish government and become a national infrastructure for large-scale bioscience. A new organization will start in the middle of 2013 when the two nodes in Stockholm and Uppsala will merge into one organization with a common board.

SciLifeLab’s vision to take part in strengthening health care, through new technologies and products, has resulted in the start up of two new areas in the center. The first one is a platform for Drug Develop-ment that will bring activities already ongoing, such as small molecule library and RNAi cell screening, under one roof and expand and complement these activities with expertise in drug development. Second, to further strengthen the collaboration and integration with the health care sector, SciLifeLab Stockholm will expand its activities with a clinical genomics facility to perform next generation sequenc-ing on patient samples with fast processing time.

During 2013 SciLifeLab Stockholm will grow with approximately 30 new research groups, encompass-ing more than 600 persons at the end of the year.

The aim is also to accommodate national and international research groups with strategically important expertise to join SciLifeLab. Fellowships will allow young research leaders to work in the interdisciplinary environment of SciLifeLab for a shorter or longer period and contribute to an even more dynamic research environment.

The links to other Swedish universities will be further strengthened during the years to come, as SciLifeLab will have a national responsibility to provide access to advanced technologies and exper-tise in bioscience. Several areas of expertise in life science at other universities will also be formally linked to SciLifeLab. The National Reference Committee, with representatives from all major Swedish universities, will continue to give strategic advice on the development of SciLifeLab and monitor the accessibility and output from the platform facilities. In order to provide access to technologies and expertise and to support knowledge exchange and the spread of new technologies, space for guests has been made available both in offices and laboratories and a program of courses, workshops and seminars will be provided.

SciLifeLab aims to be an internationally leading center for providing

and developing state-of-the-art technology and expertise in large-scale

molecular biosciences and to produce first-class interdisciplinary research.


The organization of SciLifeLab Stockholm 2012

SciLifeLab Stockholm is a collaboration between the Royal Institute of Technology (KTH), Karolinska Institutet (KI) and Stockholm University (SU). The SciLifeLab Board has the responsibility for decisions regarding the budget and strategic development of the center. The board consists of six members, two from each university. An international Scientific Advisory Board and the National Reference Committee give advice to the board.

In the end of 2012, a new operative management structure at SciLifeLab Stockholm was introduced comprising three Center Directors and three Scientific Directors, each representing one of the universities. The Center Directors are responsible for implementing the board’s decisions about the center budget and activities. Moreover, a Site Director is responsible for the day-to-day operations.

The center included seven platforms during 2012 and a number of platform facilities. The platforms represent areas of research where a combination of technologies

is generally used. The platform facilities are units each representing a certain technology and which can offer services to internal and external research groups. A number of senior researchers are appointed as Platform Directors with responsibility for the scientific develop-ment of the platforms. The day-to-day activities of the platform facilities are headed by Facility Managers.

The Affiliated Faculty of SciLifeLab Stockholm is a network of representatives from all departments, research centers and other organizations in the Stockholm region with an interest in the activities at SciLifeLab Stockholm.

In order to coordinate activities between the Stockholm and Uppsala node and plan for a common organization in 2013 a coordination committee was initiated in 2012. This committee consists of one representative from each of the four universities (KTH, SU, KI and UU).

The research leaders of SciLifeLab Stockholm are presented on page 24–25. More information about the Platform facilities and the services available can be found on page 10 and 28–45 and at www.scilifelab.se.

Fredrik Sterky Assoc. Prof. Site Director

Martina Selander Personnel and administration

Mikaela Friedman Dr., Scientific communication and External relations

Mathias Uhlén Prof. (KTH)Center Director

Gunnar von Heijne Prof. (SU)Vice Center Director

Jan Andersson Prof. (KI)Vice Center Director

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The Genomics platform is the most established platform and carried out several hundreds of research projects during 2012. It offers massively parallel DNA sequencing and bioinformatics support for projects in plants, humans, microorganisms and cell lines. With the latest instrumentation, an entire human genome can be sequenced in 27 hours. During 2013, the new technology and expertise will enable a new facility “Clinical genomics” to emerge. Next generation sequencing on patient samples will be performed in collaboration with the treating physicians and hospital geneticists.

The MS proteomics platform as well as the Function-al biology and Bioimaging platforms are also carry-ing out large numbers of projects. Other platforms, such as Affinity proteomics and Functional genomics require more detailed experimental planning and are customized for each user. In many cases, SciLifeLab Stockholm can provide unique competence and resources. One example is the Affinity Proteomics platform that uses the unique resource of affinity reagents from the Human Protein Atlas (HPA) project allowing high-throughput biomarker discov-ery screening in large cohorts of clinical samples. This platform also provides means to validate antibodies and/or cell lines in a subcellular fashion using the HPA reagents and confocal microscopy.

The Platform facilities are presented in more detail on page 28 to 45.More information about the Platform facilities is available at www.scilifelab.se.

SciLifeLab has competences in a wide range of areas that are organized in platforms, which offer state-of-the-art technologies and expertise to the research community. During 2012 the center included seven platforms; Genomics, Affinity Proteomics, Mass Spectrometry (MS) Proteomics, Functional Biology, Bioimaging, Functional Genomics and Bioinformat-ics & Systems Biology. The platforms are divided into smaller units, platform facilities that handle one or a few different technologies within the field.

Each platform facility is headed by a facility manager with responsibility for the daily work, personnel and budget. The strategic development and overall budget for the platform is managed by a platform director. In several cases, the platform facilities in Stockholm are jointly run with a similar facility at the Uppsala node. This allows efficient handling of large numbers of projects and samples. In other areas, the technologies and expertise are unique to each site.

During 2012, the number of projects carried out in the facilities has increased considerably with users from all Swedish universities. The projects cover a broad range of molecular bioscience research and considerable parts of the research being performed is focusing on an increased molecular level/mechanis-tic understanding of human diseases, plants, and microbes, finding new biomarkers for disease and development of new treatments.

The platforms offer technology infrastructure and competence

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Section of a mouse olfactory bulb. Amphiphysin is a protein associated with the cytoplasmic surface of synaptic vesicles. Autoantibodies against this protein have been associated with stiff-man syndrome. Antibodies against amphiphysin (green) stain many neurons in the mouse brain including the olfactory bulb.


Immunofluorescent staining of human MCF-7 metastatic breast adenocarcinoma cells, using an antibody HPA049798 towards Zinc finger CCCH domain-containing protein 14, shows positivity in nucleus but not nucleoli.



All cells of higher organisms such as humans or animals

are organized into compartments with specialized

functions. These so called organelles are defined by

their own chemical characteristics and molecular

composition. For example an organelle called mito-

chondrion has the function to provide energy for the

cell, whereas the cytoskeleton serves to maintain

cellular shape, movement and functions as a railroad

for intracellular transport. Thus, knowing the exact

subcellular location of a given protein is of great

importance as it indicates the protein function and

leads to a better understanding of how and why

proteins interact in networks and signaling pathways.

Ever since the human genome was first characterized much efforts has been put into the identification and characterization of the gene products – the proteins. A key to unlock a more complete understanding of the information embedded in the human genome and the complex machinery of living cells is to know the subcellular localization for every protein. As part of the Human Protein Atlas project our research is therefore focused on determining the subcellular localization of all human proteins by the use of specific antibodies and high-resolution microscopy.

During 2012, the Subcellular Protein Atlas program at SciLifeLab Stockholm has expanded in different directions, as reported in several publications. The panel of human cells has increased to fifteen cell lines of different origin from which the most suitable is

selected based on gene transcript expression levels (1). Furthermore, a pipeline for validation of antibody binding and protein subcellular location using siRNA (2) and automated classification of staining patterns (3) has been developed. Beyond this, we have demonstrated the added value of using a complementary technique such as live cell imaging of tagged proteins to allow a complete investigation of the subcellular human proteome (4).

Currently, the Subcellular Protein Atlas contains ~100,000 images corresponding to the localization of over 12,000 proteins. The aim of the presented atlas is to make subcellular information for all human proteins publicly available, with the ultimate aim to facilitate functional studies of proteins.

References1. Danielsson, F. et al (2013) “RNA Deep Sequencing as a Tool for

Selection of Cell Lines for Systematic Subcellular Localization of All Human Proteins” J Proteome Res. 12 (1): 299-307.

2. Stadler, C. et al (2012) “Systematic validation of antibody binding and protein subcellular localization using siRNA and confocal microscopy” J Proteomics 75 (7): 2236-51.

3. Li, J. et al (2012) “Estimating Microtubule Distributions from 2D Immunofluorescence Microscopy Images Reveals Differences among Human Cultured Cell Lines” PLoS One. 7 (11): e50292.

4. Stadler, C. et al (2013) “Immunofluorescence and fluorescent- protein tagging show high correlation for protein localization in mammalian cells” Nat Methods, in press.

Contact

Emma Lundberg

E-mail: [email protected]

The Subcellular Protein Atlas

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Cancers are characterized by genetic mutations and an

overall high load of DNA damage, which can be

exploited for novel therapies. Our laboratory focuses

on a multidisciplinary approach to understand basic

properties of DNA repair at a molecular level, and

identify and validate novel protein targets within the

DNA repair pathway (1, 2). Using an open innovation

approach, in close collaboration with academic groups

and clinicians, we develop small molecule inhibitors to

novel targets that are tested in early proof of concept

trials in patients.

Cancer remains the most common cause of death for individuals aged below 80 in industrialized countries and novel more effective treatments for cancer are urgently needed. Traditional radio- and chemo-therapy work by causing an unbearable load of DNA damage in cancer cells, which effectively eradicate the cancer, but also cause harmful side effects. Our aim is to selectively introduce DNA damage in tumors without harming non-malignant cells. We previously demonstrated that cancers caused by mutations in BRCA1 or BRCA2 genes rely on PARP for survival and that PARP inhibitors can selectively kill off the cancers (3). This is now tested in numerous clinical trials. Based on this new concept of synthetic lethality, we are identifying genes that are required for survival only in the mutated cancer cells.

One characteristic of most cancers is a high level of oxidative damage, which helps in generating mutations

required for cancer development. However, to avoid lethal DNA damage cancer cells appear dependent on new proteins to survive; such as nucleotide hydrolases. By specifically targeting nucleotide hydrolases we have identified a new strategy to attack cancer. We have developed small molecule inhibitors against these proteins, which kill cancer cells without harming normal growing cells. Our most effective inhibitors will be further optimized, tested in in vivo tumor models and passed on to clinical trials with the aim of treating cancer patients.

By working in a multidisciplinary fashion we are able to combine expertise from several disciplines such as biochemistry, medicinal chemistry, molecular biology, clinical oncology and pharmacology. In addition, we are fortunate to have a number of collaborations, both national and international, across a range of disciplines to complement our in-house expertise.

References1. Groth, P. et al (2012) “Homologous recombination repairs

secondary replication induced DNA double-strand breaks after ionizing radiation” Nucleic Acids Res. 40 (14): 6585-94.

2. Elvers, I. et al (2012) “CHK1 activity is required for continuous replication fork elongation but not stabilization of post-replicative gaps after UV irradiation” Nucleic Acids Res. 40 (17): 8440-8.

3. Bryant, H.E. et al (2005) “Specific killing of BRCA2-deficient tumors with inhibitors of poly(ADP-ribose)polymerase” Nature, 434 (7035): 913-7.

Contact

Thomas Helleday


Targeting DNA repair to find novel anti-cancer treatments



All cells are surrounded by a lipid membrane that

separates them from the outside world and protect

their content. Cell membranes are stuffed full of

proteins. Membrane proteins are central players in all

types of cells, from bacteria to man. They make it

possible for cells to take up nutrients from the environ-

ment, to excrete waste products, and to receive and

transmit various kinds of signals from other cells. Being

the gatekeepers of the cell, membrane proteins are also

favorite drug targets; it is estimated that more than half

of all drugs currently on the market bind to and change

the activity of membrane proteins.

Much effort is currently spent across the world to determine high-resolution structures of membrane proteins in order to understand their function on the molecular level. But in order to fully understand membrane proteins, structures are not enough. We also need to figure out how membrane proteins are manu-factured in the cell, how they are inserted into the membrane, and how they fold into the final structure. This is important not only from a basic science perspec-tive, but also to understand how mutations in medically important membrane proteins can cause proteins to misfold and thereby destroy their function.

Our research is focused on these early stages in the life of membrane proteins. In particular, we have recently been able to discover some “tricks” that nature has invented in order to make membrane proteins with membrane-embedded parts that by themselves cannot

enter a membrane (1). This has been a conundrum, but we now understand the basic principles. Another advance is the development of a new method that allows us to measure forces acting on membrane proteins during their insertion into the membrane (2). This has not been possible before, and opens up a new window for probing the molecular mechanisms that underlie membrane protein folding in the cell. References1. Öjemalm, K. et al (2012) “Orientational preferences of neighboring

helices can drive ER insertion of a marginally hydrophobic transmembrane helix” Molecular Cell 45 (4): 529-40.

2. 1Ismail, N. et al (2012) “A bi-phasic pulling force acts on transmem-brane helices during translocon-mediated membrane integration” Nature Structural and Molecular Biology 19 (10): 1018-22.

1Editor’s Choice, Science 19 October 2012

Contact

Gunnar von Heijne


Membrane protein biogenesisTargeting DNA repair to find novel anti-cancer treatments

A typical membrane protein. This particular protein, called EmrE, helps bacteria extrude toxic compounds such as antibiotics through their membrane.



After the human genome was sequenced in 2000, it was

hoped that the knowledge of the entire sequence of

human DNA could rapidly be translated to medical benefits

such as novel drugs, and predictive tools that would

identify individuals at risk of disease. However, this turned

out to be harder than expected, one of the reasons being

that only the 1% of the genome that codes for proteins

could be read. The remaining 99% contains information

about when and where these proteins are made, and is to

us like a book written in a foreign language – we know the

letters but cannot understand why a human genome

makes a human or the mouse genome a mouse. Why some

individuals have higher risk to develop common diseases

such as heart disease or cancer is even less well understood.

The Taipale group addresses this problem by studying the

human proteins that read the gene regulatory code:

transcription factors (TFs).

The human genome encodes approximately 1000 TFs, and they bind specifically to short 5 to 20 base pair sequences of DNA, and control production of other proteins. Through the use of a highly automated laboratory, we have identified DNA sequences that bind to over 400 such proteins, representing approximately half of all human TFs. We have also developed compu-tational tools that can use such information to identify gene variants that are linked to disease. We have analysed one particular single nucleotide variant in a region associated with increased risk for developing colorectal and prostate cancers. Although

this variant increases cancer risk only by 20 per cent, it is very common and therefore accounts for more inherited cancer than any other currently known genetic variant or mutation. We removed the gene region containing the risk variant from the mouse genome and found that as a result the mice were healthy, but displayed a small decrease in the expres-sion of a nearby cancer gene, called MYC. However, when these mice were tested for the ability to form tumors after activation of an oncogenic signal that causes colorectal cancer in humans, they showed dramatic resistance to tumor formation. The removed gene region thus appears to act as an important gene switch promoting cancer, and without it tumors develop much more rarely. This study highlights that growth of normal cells and cancer cells is driven by different gene switches, suggesting that further work to find ways to control the activity of such disease-specific switches could lead to novel, highly specific approaches for therapeutic intervention.

References1. Kivioja, T. et al (2012) “Counting absolute number of molecules

using unique molecular identifiers” Nature Methods 9 (1): 72-4.2. Sur, I. et al (2012) “Mice Lacking a Myc Enhancer Element that

Includes Human SNP rs6983267 Are Resistant to Intestinal Tumors” Science 338 (6112): 1360-3.

3. Jolma, A. et al (2013) “DNA-binding specificities of human transcription factors” Cell 152: 327-39.

Contact

Jussi Taipale


Reading the Genome



The sodium pump is a very important protein in the

mammalian cell. While pumping sodium and potassium

ions it consumes 30% of all energy in the body and 60%

of the energy in the brain. Surprisingly, the full picture

of how this protein functions in the human brain is not

clear. Researchers at SciLifeLab are studying the sodium

pump in neurons to understand its role in health and

disease. How it is regulated to preserve energy. How it

acts as a signaling protein. How identified disease

mutations influence its function.

Recent studies have shown that the sodium pump, Na,K-ATPase, not only pumps ions but also has an important role as a signal transducer (1). We have shown that binding of cardiotonic steroids to Na,K-ATPase trigger frequency modulated Ca2+ oscilla-tions with downstream anti-apoptotic effects.

The functional significance of neuronal expression of two different isoforms of Na,K-ATPase, a1 and a3, has been studied by intracellular Na+ imaging. The a3 isoform, which has a higher Na+ affinity than a1, was identified to have a specific role in restoration of intracellular Na+ after the transient influx that occurs during synaptic activity (2).

Applying super resolution microscopy (STED, PALM, SIM) we revealed for the first time the discrete localization of the neuron specific a3 isoform to the neck of dendritic spines (3) and also the spatial interrelationship to dopamine D1R receptors (4).

Super localization microscopy of quantum dot labeled Na,K-ATPase showed that mobility and temporal confinements of the sodium pump in the plasma membrane is a key component for the energy efficient regulation of Na+.

References1. Li, J. et al (2010) “Ouabain protects against adverse developmental

programming of the kidney” Nature Communications, 1: 42.2. Azarias, G. et al (2013) “A specific and essential role for Na,K-

ATPase a3 in neurons co-expressing a1 and a3” J Biol Chem. 288 (4): 2734-43.

3. Blom, H. et al (2011) “Spatial distribution of Na+-K+-ATPase in dendritic spines dissected by nanoscale superresolution STED microscopy” Bmc Neuroscience 12:16.

4. Blom, H. et al (2012) “Nearest neighbor analysis of dopamine D1 receptors and Na(+) -K(+) -ATPases in dendritic spines dissected by STED microscopy” Microsc Rese Tech. 75 (2): 220-8.

Contact

Hjalmar Brismar


Na,K-ATPase – an overlooked protein in the brain

Na,K-ATPase a3 is enriched in dendritic spines in hippocampal neurons. Super resolution microscopy of Na,K-ATPase a3 in dendritic spines of a hippocampal neuron. Lower panel show an overlaid confocal micrograph of PSD95 (red) on the super resolution image (grey).



The human body comprises over 100 trillion cells and is

organized into more than 200 different organs and

tissues. The development and organization of complex

organs, such as the brain, are far from understood and

there is a need to dissect the expression of genes using

quantitative methods. The organs are in themselves a

mixture of differentiated cells to enable all body

functions such as nutrient transport, defense etc.

Consequently, cell function is context dependent, and

the context provided by tissue structure is being

disentangled at the transcriptional level within the

spatial transcriptomics project.

The new advances in high-throughput genomics have reshaped the biological research landscape and in addition to complete characterization of genomes we are also able to study the full tran-scriptome in a digital and quantitative fashion. The bioinformatics tools to visualize and integrate these comprehensive sets of data have also been significantly improved during recent years. Findings by deep RNA sequencing have demon-strated that a majority of the human genes are active in a cell and that a large fraction (75%) of the human protein-coding genes are expressed in most tissues. The transcriptional machinery can therefore be described to be promiscuous at a global level but remains dynamically complex, demonstrated by burst transcription, where brief pulses of transcription are separated by periods of transcriptional silence.

We have recently devised a simple strategy that enables global gene expression analysis in histological tissue sections, yielding transcriptomic information with two-dimensional spatial resolution. This enables the identification of individual transcriptomes of single cells while maintaining the positional information of those cells in the tissue. The RNA sequencing data is visual-ized in the computer together with the tissue section, for instance to display the expression pattern of a gene of interest across the tissue. It is also easy to mark different areas of the tissue section on the computer screen and obtain information on differentially expressed genes between any selected areas of interest.

We are currently creating spatial transcriptional maps of the brain, arguably the most complex organ in the body, with at least hundreds of different distinct neuronal subtypes that are interconnected in precise patterns. Our aim is to improve understanding of neurological and psychiatric diseases, as our current knowledge is still limited, contributing to the difficulty in developing therapies for many of these diseases. Psychiatric and neurological diseases cause much suffering of affected patients and their families and enormous costs to society.

ReferencesPatent PCT/EP2012/056823

Contact

Joakim Lundeberg


Spatial transcriptomics of the brain


Data analysis. The data from the spatial transcriptomics experiment is visualized in the spatial transcriptomics viewer software. Virtual analysis of the tissue section is enabled and the user can select and analyze the gene expression in a cell or an area of interest. The user can also look at differential expression between selected regions, or perform an automated virtual analysis for identification of cell types based on predefined expression profiles.



Ion channels that open and close in response to

electrical signals are membrane proteins that constitute

the fundamental building blocks responsible for e.g.

our nerve signaling and heartbeats. These channels

sense differences in voltage across a cellular membrane

with four special voltage sensor parts (domains) whose

structure changes. It has previously not been possible to

determine how these changes occur. During the last

year, we were able to solve this problem with a new

combination of experiments, bioinformatics and

simulations, which now enables us to track a complete

cycle of a voltage sensor activation in response to

voltage in full atomic detail.

Since it is difficult or impossible to determine a crystal structure with a voltage applied, the only structures available this far have corresponded to the open state of the Kv1.2-2.1 potassium channel. However, in collaboration with Linköping University we have been able to design electrophysiology experiments that capture information from interme-diate states only visited briefly during channel opening or closing. This provides a wealth of new indirect structural information, and in combination with molecular modeling and molecular simulation it enabled us to predict a range of five different atomic-detail models corresponding to states ranging from fully activated to resting voltage-sensor domains (1). This results in a virtual movie of the complete cycle of structural changes of the ion channel, and makes it possible to explain how the gating occurs. For each

intermediate stage, one more charge in a specific part of the protein is moved across a hydrophobic region in the core of the ion channel, which effectively moves it from one side of the membrane to the other (2). We have also been able to use combined experiments and simulations to show that a specific residue (F233) in this region is responsible for making the closing process of potassium channels very slow (3). This likely explains a key property of our nerve system, where all nerve impulses are created by fast (sodium) channels first opening to depolarize the membrane, followed by the slower potassium channel opening to restore the equilibrium – if the latter closed instantly the nerve system would not work.

References1. Henrion, U. et al (2012) “Tracking a complete voltage-sensor cycle

with metal-ion bridges” Proc. Natl. Acad. Sci. 109 (22): 8552-57.2. Lindahl, E. (2012) “Unraveling the strokes of ion channel molecular

machines in computers” Proc. Natl. Acad. Sci. 109 (52): 21186-87.3. Schwaiger, C.S. et al (2012) “The conserved phenylalanine in the

k(+) channel voltage-sensor domain creates a barrier with unidirectional effects” Biophys J. 104: 75-84.

Contact

Erik Lindahl


Understanding the molecular basis of nerve signalsTracking the activation cycle of a voltage-gated ion channel


Deactivation of voltage sensor from a voltage-gated ion channel. As the voltage changes, the sensor moves through intermediate states to a resting state where it will push on the pore domain (not shown) to close the channel.



As more and more high-throughput biological data is

generated, there is a growing need to understand how

genes and proteins are organized in networks. We have

developed a bioinformatics framework for mapping

diverse types of data into a single network of functional

couplings. Such network maps are a tremendous

resource for identifying the functional partners of

genes and proteins, and to analyze relations between

groups of genes. To this end, we have developed

bioinformatics tools to assess the statistical significance

of network crosstalk between gene groups. We are also

elucidating gene regulatory networks by perturbation

experiments and improved bioinformatics methodology.

Network biolog y. FunCoup is a data integration project for producing global comprehensive gene/protein networks of functional couplings. Release 2.0 was built using 9 different types of high-throughput data from 11 different species (1). FunCoup achieves its high coverage by orthology-based transfer of functional coupling between species. The FunCoup website http://FunCoup.sbc.su.se provides unique facilities for analyzing network context of query genes and the conservation of subnetworks in multiple species.

Functional analysis. The FunCoup networks can be used for pathway annotation of gene lists using ”Network Crosstalk Enrichment Analysis”. This measures enrichment of network crosstalk between an experi-mentally derived gene list and known pathways. We have shown that this approach yields

a 5-fold increase in sensitivity compared to tradition-al gene enrichment analysis, which does not use a network (2). Moreover, we have developed an efficient and highly accurate bioinformatics method that improves gene list analysis by clustering the genes into distinct functional groups (3).

Systems biolog y. Dynamic transcriptional gene regulatory networks can be inferred by perturbing some genes, e.g. with RNA interference, and measur-ing the effect this has on other genes. Several model-ing techniques exist for such inferences, but a major problem has been estimating the sparsity of the network, leading to very poor accuracy. To resolve this, we have developed a method that, given suffi-ciently informative data, predicts the optimal sparsity and produces correct regulatory networks (4). Together with SciLifeLab facilities, we are elucidat-ing gene regulatory networks relevant to cancer.

References1. Andrey, A. et al (2012) “Comparative interactomics with Funcoup

2.0” Nucleic Acids Research 40: D821-D828.2. McCormack, T. et al (2013) “Statistical Assessment of Crosstalk

Enrichment between Gene Groups in Biological Networks” PLoS ONE 8: e54945.

3. Frings, O. et al (2013) “MGclus: network clustering employing shared neighbors” Molecular BioSystems (in press).

4. Tjärnberg, A. (2013) “Optimal sparsity criteria for network inference” J. Computational Biology (in press)

Contact

Erik Sonnhammer


Bioinformatics for network and systems biology


research program has also been established for collaborations between AstraZeneca and SciLifeLab associated groups.

Example of collaboration: GE Healthcare

The GE Healthcare DemoLab is a facility equipped with GE Healthcare’s instrumentation and reagents for life science research. This complements the instrumentation and competence provided by SciLife-Lab and facilitates collaboration between industry and academia. The instrumentation includes ÄKTA for purification and analysis of biomolecules, Biacore and MicroCal technology for biomolecular interaction analysis and the imaging systems Image Quant and Typhoon, and IN Cell Analyzer. During 2012, GE DemoLab has been carrying out a large number of projects together with research groups in the Stockholm-Uppsala region.

Based on the advanced technologies and instrumen-tation available, SciLifeLab Stockholm aims to be involved in the development of new techniques and instrumentation in collaboration with industry and to be a reliable and competent partner for develop-ment and testing of new technology. Several such collaborations are ongoing at SciLifeLab Stockholm.

Another interesting possibility for industrial collabo-ration is to get smaller companies to use the resources at SciLifeLab as means for increasing their interna-tional competitiveness. This will be based on a full-cost policy, but might still be attractive for some companies.

Finally, SciLifeLab Stockholm is an attractive partner for pharmaceutical industry in larger scientific studies. One interesting possibility here is to use the infrastructure built up in SciLifeLab along with Sweden’s unique clinical materials and skills to promote Sweden as a location for research on the major international pharmaceutical companies.

Example of collaboration: AstraZeneca

In June 2012, AstraZeneca started up the Translational Science Centre in collaboration with Karolinska Institutet. The center is situated at SciLifeLab Stockholm and will be focusing on finding biomarkers for different chronic diseases, such as cancer, rheumatoid arthritis, cardiovascular disease and dementia. A joint collaborative open

Collaboration with industry

GE Healthcare DemoLab.

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an E

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on

Collaborations between academia and industry are becoming increasingly important

and SciLifeLab Stockholm is working actively to find new forms of collaboration with

national and international industry partners. These collaborations have large

potential for societal gains in a wide range of applications. Examples range from a

faster route to convert new knowledge into products or therapies in medicine and

health care to new ways to produce biofuels.


The SciLifeLab Stockholm researchers

Adnane AchourAssoc. Prof., KIStructural and Biophysical Immunol-ogy.

Afshin AhmadianAssoc. Prof., KTHExperimental genomics.

Anders AnderssonAssoc. Prof., KTHMetagenomic analysis of microbial communities.

Björn AnderssonProf., KIGenomic analysis.

Lars ArvestadDr., SUComputational studies in evolution and genomics.

Helena BerglundAssoc. Prof., KIFacility Manager Protein Production.

Thomas HelledayProf., KITranslational cancer medicine and chemical biology.

Berk HessAssoc. Prof., SUComputational biophysics.

Lukasz HuminieckiAssoc. Prof., SUComputational biology statistics, bioinformat-ics and software development.

Annika Jenmalm Jensen Dr., KIFacility manager Chemical Biology. Director of Chemical Biology Consortium Sweden (CBCS).

Juha KereProf., KIMolecular genetics and biology of complex phenotypes.

Lukas KällAssoc. Prof., KTHStatistical biotechnol-ogy.

Mats NilssonProf., SUMolecular diagnostics.

Peter NilssonProf., KTHSite Director of Human Protein Atlas at SciLifeLab.

Jacob OdebergProf., KTH/KIClinically applied proteomics.

Bengt PerssonProf., KI/LiUDirector of BILS (Bioinformatics Infrastructure for Life Sciences). Protein families and structural properties.

Peter SavolainenAssoc. Prof., KTHEvolutionary studies of dogs based on DNA sequence analysis.

Jochen SchwenkAssoc. Prof., KTHFacility manager Biobank profiling. Biomarker discovery using antibody-based analysis of biobank samples.


Hjalmar BrismarProf., KTH/KIDevelopment of methods based on superresolution microscopy with applications in studies of membrane proteins and their integrative functions.

Jens CarlssonDr., SUComputational structural and chemical biology.

Arne ElofssonProf., SUStudies of protein structure, folding and evolution using mainly computational methods.

Olof EmanuelssonAsst. Prof., KTHBioinformatics of gene expression and protein localization.

Lars EngstrandProf., KIClinical bacteriology.

Gunnar von HeijneProf., SUVice Center Director. Experimental and bioinformatics studies of membrane proteins.

Jens LagergrenProf., KTHEvolution, probabilistic modeling, RNA editing, micro RNA, machine learning, and algorithm design.

Janne LehtiöAssoc. Prof., KIFacility manager Clinical Proteomics and Director of Karolinska University Hospital proteomics facility. In-depth analysis of proteome, mass spectrometry.

Erik LindahlProf., SU/KTHBiophysics. Modeling, simulation and electrophysiology studies of voltage- and ligand-gated ion channels. Leading the GROMACS interna-tional molecular simulation project.

Emma LundbergAssoc. Prof., KTHFacility manager Cell Profiling. Protein profiling of cells using antibody-based imaging.

Joakim LundebergProf., KTHDevelopment and application of novel methods for massively parallel DNA sequencing.

Jan MulderDr., KIFacility manager Tissue Profiling. Antibody-based mapping of regional and cellular protein distributions in the mammalian nervous system.

Erik SonnhammerProf., SUDirector of Stockholm Bioinformatics Centre. Prediction of protein function and interaction networks.

Jussi TaipaleProf., KIDirector of KHTC. Studies of the molecular mechanisms behind the develop-ment of cancer, including gene expression.

Mathias UhlénProf., KTHCenter Director. Leading the international effort to create a Human Protein Atlas.

Anna WedellProf., KIMedical genetics and discovery of novel monogenic diseases.

Roman ZubarevProf., KIMass-spectrometry based proteomics for biomedical research.

Björn ÖnfeltAssoc. Prof., KTHImmune cell diagnostics.


Contreras et al (2012), Nature 481 (7382): 525-9.Molecular recognition of a single sphingolipid species by a protein’s transmembrane domain.

Darki et al (2012), Biol Psychiatry 72 (8): 671-6.Three Dyslexia Susceptibility Genes, DYX1C1, DCDC2, and KIAA0319, Affect Temporo-Parietal White Matter Structure.

Dengjel et al (2012), Mol Cell Proteomics 11 (3): M111 014035.Identification of autophagosome-associated proteins and regulators by quantitative proteomic analysis and genetic screens.

Ekdahl et al (2012), Genome Res 22 (8): 1477-87.A-to-I editing of microRNAs in the mammalian brain increases during development.

Elvers et al (2012), Nucleic Acids Res 40 (17): 8440-8.CHK1 activity is required for continuous replication fork elongation but not stabilization of post-replicative gaps after UV irradiation.

Eriksson et al (2012), Blood Cancer J 2: e81.The novel tyrosine kinase inhibitor AKN-028 has significant antileukemic activity in cell lines and primary cultures of acute myeloid leukemia.

Forslund et al (2012), Methods Mol Biol 856: 187-216.Evolution of protein domain architectures.

Fraser et al (2012), Clin Cancer Res 18 (4): 1015-27.PTEN deletion in prostate cancer cells does not associate with loss of RAD51 function: implications for radiotherapy and chemotherapy.

Groth et al (2012), Nucleic Acids Res 40 (14): 6585-94.Homologous recombination repairs secondary replication induced DNA double-strand breaks after ionizing radiation.

Gubanova et al (2012), Clin Cancer Res 18 (5): 1257-67.Downregulation of SMG-1 in HPV-positive head and neck squamous cell carcinoma due to promoter hypermethylation correlates with improved survival.

Guy et al (2012), Proc Natl Acad Sci U S A 109 (52): E3627-8.Genomic diversity of the 2011 European outbreaks of Escherichia coli O104: H4.

Aavikko et al (2012), Am J Hum Genet 91 (3): 520-6.Loss of SUFU Function in Familial Multiple Meningioma.

Abrahamsson et al (2012), J Allergy Clin Immunol 129 (2): 434-40.Low diversity of the gut microbiota in infants with atopic eczema.

Ahmad et al (2012), Mol Cell Proteomics 11 (3): M111 013680.Systematic analysis of protein pools, isoforms, and modifications affecting turnover and subcellular localization.

Alexeyenko et al (2012), Nucleic Acids Res 40: D821-8.Comparative interactomics with Funcoup 2.0.

Arabi et al (2012), Nat Commun 3: 976.Proteomic screen reveals Fbw7 as a modulator of the NF-kappaB pathway.

Bäcklund et al (2012), Ann Rheum Dis (in press).C57BL/6 mice need MHC class II Aq to develop collagen-induced arthritis dependent on autoreactive T cells.

Buus et al (2012), Mol Cell Proteomics 11 (12): 1790-800.High-resolution Mapping of Linear Antibody Epitopes Using Ultrahigh-density Peptide Microarrays.

Carlsson et al (2012), Methods Mol Biol 857: 313-30.Investigating protein variants using structural calculation techniques.

Chauhan et al (2012), Cancer Cell 22 (3): 345-58.A small molecule inhibitor of ubiquitin-specific protease-7 induces apoptosis in multiple myeloma cells and overcomes bortezomib resistance.

Chingin et al (2012), Anal Chem 84 (15): 6856-62. Separation of Polypeptides by Isoelectric Point Focusing in Electrospray-Friendly Solution Using a Multiple-Junction Capillary Fractionator.

SciLifeLab Stockholm – Scientific publications

During 2012, SciLifeLab Stockholm researchers have

produced more than 170 scientific publications. The list

below presents all peer-reviewed scientific publications

in journals with an impact factor of six or higher.


Hansson et al (2012), Lab Chip 12 (22): 4644-50.Inertial microfluidics in parallel channels for high-throughput applications.

Henrion et al (2012), Proc Natl Acad Sci U S A 109 (22): 8552-7.Tracking a complete voltage-sensor cycle with metal-ion bridges.

Hirvikoski et al (2012), J Clin Endocrinol Metab 97 (6): 1881-3.Prenatal dexamethasone treatment of children at risk for congenital adrenal hyperplasia: the Swedish experience and standpoint.

Imai et al (2013), Methods Mol Biol 939: 115-40.Localization prediction and structure-based in silico analysis of bacte-rial proteins: with emphasis on outer membrane proteins.

Ismail et al (2012), Nat Struct Mol Biol 19 (10): 1018-22.A biphasic pulling force acts on transmembrane helices during translocon-mediated membrane integration.

Jones et al (2012), Oncogene (in press).Increased replication initiation and conflicts with transcription underlie Cyclin E-induced replication stress.

Kampf et al (2012), BMC Med 10: 103.A tool to facilitate clinical biomarker studies - a tissue dictionary based on the Human Protein Atlas.

Kivioja et al (2012), Nat Methods 9 (1): 72-4.Counting absolute numbers of molecules using unique molecular identifiers.

Kjellqvist et al (2012), Mol Cell Proteomics 12 (2): 407-25.A combined proteomic and transcriptomic approach shows diverging molecular mechanisms in thoracic aortic aneurysm development in patients with tricuspid- and bicuspid aortic valve.

Lamminmaki et al (2012), J Neurosci 32 (3): 966-71.Human ROBO1 regulates interaural interaction in auditory pathways.

Larance et al (2012), Mol Cell Proteomics 11 (3): M111 014407.Characterization of MRFAP1 turnover and interactions downstream of the NEDD8 pathway.

Liebmann et al (2012), J Neurosci 32 (50): 17998-8008.A Noncanonical Postsynaptic Transport Route for a GPCR Belonging to the Serotonin Receptor Family.

Lindahl (2012), Proc Natl Acad Sci U S A 109 (52): 21186-7.Unraveling the strokes of ion channel molecular machines in computers.

Logue et al (2012), ISME J 6 (6): 1127-36.Freshwater bacterioplankton richness in oligotrophic lakes depends on nutrient availability rather than on species-area relationships.

Nikulenkov et al (2012), Cell Death Differ 19 (12): 1992-2002.Insights into p53 transcriptional function via genome-wide chromatin occupancy and gene expression analysis.

Nookaew et al (2012), Nucleic Acids Res 40 (20): 10084-97.A comprehensive comparison of RNA-Seq-based transcriptome analysis from reads to differential gene expression and cross-compar-ison with microarrays: a case study in Saccharomyces cerevisiae.

Öjemalm et al (2012), Mol Cell 45 (4): 529-40.Orientational preferences of neighboring helices can drive ER insertion of a marginally hydrophobic transmembrane helix.

Öjemalm et al (2012), J Cell Sci (in press).Positional editing of transmembrane domains during ion channel assembly.

Perisic et al (2012), Kidney Int 82 (10): 1071-83.Plekhh2, a novel podocyte protein downregulated in human focal segmental glomerulosclerosis, is involved in matrix adhesion and actin dynamics.

Punta et al (2012), Nucleic Acids Res 40: D290-301.The Pfam protein families database.

Renvall et al (2012), J Neurosci 32 (42): 14511-8.Genome-wide linkage analysis of human auditory cortical activation suggests distinct Loci on chromosomes 2, 3, and 8.

Sandberg et al (2012), Mol Cell Proteomics 11 (7): M112 016998.Tumor proteomics by multivariate analysis on individual pathway data for characterization of vulvar cancer phenotypes.

Slaats et al (2012), Allergy 67 (7): 895-903.DNA methylation levels within the CD14 promoter region are lower in placentas of mothers living on a farm.

Somaiah et al (2012), Clin Cancer Res 18 (19): 5479-88.The Relationship Between Homologous Recombination Repair and the Sensitivity of Human Epidermis to the Size of Daily Doses Over a 5-Week Course of Breast Radiotherapy.

Sur et al (2012), Science 338 (6112): 1360-3.Mice Lacking a Myc Enhancer That Includes Human SNP rs6983267 Are Resistant to Intestinal Tumors.

Tammimies et al (2012), Biol Psychiatry (in press).Molecular Networks of DYX1C1 Gene Show Connection to Neuronal Migration Genes and Cytoskeletal Proteins.

Uddenberg et al (2012), Plant Physiol 161 (2): 813-23.Early cone-setting in Picea abies var. acrocona is associated with increased transcriptional activity of a MADS-box transcription factor.

Uhlen et al (2012), Mol Cell Proteomics 11 (3): M111 013458.Antibody-based protein profiling of the human chromosome 21.

Wiklund et al (2012), Lab Chip 12 (18): 3221-34.Acoustofluidics 18: Microscopy for acoustofluidic micro-devices.

Wright et al (2012), Mol Cell Proteomics 11 (8): 478-91.Enhanced peptide identification by electron transfer dissociation using an improved Mascot Percolator.

Ying et al (2012), Cancer Res 72 (11): 2814-21.Mre11-Dependent Degradation of Stalled DNA Replication Forks Is Prevented by BRCA2 and PARP1.

Zeiler et al (2012), Mol Cell Proteomics 11 (3): O111 009613.A Protein Epitope Signature Tag (PrEST) library allows SILAC-based absolute quantification and multiplexed determination of protein copy numbers in cell lines.

See more publications at publications.scilifelab.se



Facility Manager: Dr . Max Käller

Mission

• To provide a state-of-the-art infrastructure and

internationally competitive service for massively parallel

sequencing

• To provide a wide repertoire of sequencing applications

addressing the needs of national and international

customers

• To provide guidelines and support for sample collections,

study design and protocol selection

Description of service

The massively parallel DNA sequencing techniques can be

used for a variety of studies: whole genome sequencing,

exome sequencing, de novo sequencing, targeted sequenc-

ing of regions in single or multiple individuals, transcriptome

profiling including quantification, transcript isoforms and

miRNAs, ChIP-Seq to detect transcription binding sites

across the genome, amplicons sequencing (e .g ., 16S rRNA

genes), and metagenomic sequencing of microflora

genomes . The unit offers advice on project design, sample

preparation, and sequence analyses in collaboration with

the Genomics Bioinformatics facility . During 2012, the

sequencing capacity has been increased >3-fold to improve

the handling also of large sequencing projects .

As of Jan 1, 2013 the Genomics Platform operates three

facilities; Genomics Production, Genomics Applications and

Genomics IT, replacing Genomics Experimental and

Genomics Bioinformatics .

Infrastructure (selected)

• 5 Illumina HiSeq2500

• 2 Roche Genome Sequencer 454 FLX+

• 1 Life Technologies SOLiD 5500 XL

• 2 Illumina MiSeq

• 1 Argus Optical Mapper

Achievements 2012

• 207 projects completed

• 4539 samples processed

Contact

Genomics Production

Facility Manager: Dr. Ellen Sherwood


Phone: +46 8 524 81483

Genomics Applications

Facility Managers: Dr. Max Käller and Dr.Valtteri Wirta

E-mail: [email protected] or

[email protected]

Phone: +46 8 524 81426 or +46 8 524 81545

Ordering (sample coordinator): Mattias Ormestad


Phone: +46 8 524 81435

https://portal.scilifelab.se/genomics/

Genomics Experimental


• CLCbio server

• Access to computing and storage resources at UPPNEX

Software:

• BCBIO, semi-automatic software pipeline for data

management and best practice data analysis

• Adhoc, web service for analysis of proprietary

sequence data

• LIMS for management of lab data

• CLCbio, commercial software for analysis of NGS data

• Access to open source software for NGS data analysis

at UPPNEX

Achievements 2012

• Received and handled genomics data from 207 projects

and 4539 samples (an amount corresponding to on

average 82 GB per day)

• Establishment of improved best practice data analysis for

the sequencing applications provided by the Genomics

Experimental facility

• Contribution to relevant open source projects

• Successfully evaluated and received funding for establish-

ment of a national infrastructure for applied bioinformat-

ics (WABI)

Contact

Facility Managers: Dr. Thomas Svensson and

Dr. Per Kraulis


[email protected]

Phone: +46 8 524 81488 or +46 8 524 81465


Facility Manager: Dr . Thomas Svensson

Mission

• To provide state-of-the-art data handling and storage

solutions for massively parallel sequencing data

• To offer best practice data analysis aligned to the sequenc-

ing applications provided by the Genomics Experimental

facility


The facility is closely integrated with the Genomics Experimen-

tal facility and provides an automatic pipeline for transfer of

data from instruments to high-performance computing

resources . Users of the service can also benefit from a secure

web application allowing similarity searches of their own

sequence databases . The facility provides support in the form

of best practice bioinformatics analysis of genomics sequence

data, as well as applied bioinformatics analysis in various

biological contexts .

During the second half of 2012 the organization has adapted to

the 3-fold increase in data production, by focusing the informat-

ics resources on support for data production and improved best

practice analyses . The responsibility for user support of

advanced and applied bioinformatics has gradually been moved

to a new SciLifeLab facility called WABI (see more on page 44) .


Hardware:

• 2 servers dedicated for sequence assembly with

1 and 2 TB RAM memory, respectively

• Dedicated servers for data management and software

development/testing

Genomics Bioinformatics



Facility Manager: Assoc . Prof . Emma Lundberg

Mission

• To provide multiplex immunofluorescence and high-

resolution microscopy for analysis of the subcellular

distribution of proteins in a multitude of human cells

• To provide a publically available database of the sub-

cellular localization of all human proteins (Subcellular

Protein Atlas as part of the Human Protein Atlas)

• To validate the specificity of antibodies using siRNA

technology

• To provide expertise for immunofluorescence application

testing of antibodies

• To provide expertise for deeper quantitative analysis and

cell profiling in collaborative projects


The cell profiling facility has equipment and expertise to

explore the subcellular distribution of the human proteome

using antibodies and confocal microscopy . The unit provides

expertise on antibody-based high-content imaging and

extraction of quantitative and qualitative information from

images . The main activity in the Cell profiling facility is to

generate a publically available database of subcellular

protein localization of the human proteome .


• 37,000 antibodies validated (by protein arrays) from

the HPA project

• 3x Leica SP5 confocal microscopes with Screening

software

• 2x EVO150 liquid-handling robot

Achievements 2012

• 20,500 samples analysed (immunostained cell sample

prepared, imaged and analysed)

• > 100,000 confocal images acquired

• Established a platform for high-throughput validation of

antibody specificity using siRNA technology

• 15 peer-reviewed publications of which 9 related to

collaborative projects

• 10 service projects initiated (all with industry)

Contact

Facility Manager: Assoc. Prof. Emma Lundberg


Phone: +46 8 524 81468

Cell Profiling

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Lin

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Facility Manager: Assoc . Prof . Jochen Schwenk

Mission

• To provide multiplexed antibody- and antigen-based

profiling of body fluids

• To enable protein biomarker discoveries and verification

across diseases

• To provide profiling of autoimmune signatures

• To provide guidelines for sample collection and target

selection

• To support studies with data analysis and study design


The Biobank profiling facility provides support for profiling of

body fluids on three levels: study design, protein profile

generation, and statistical analyses of data . During 2012, the

service infrastructure has expanded with collaborative

projects involving research groups in the Stockholm–Uppsala

region . These projects have involved both antigen-based

profiling for new autoimmunity targets and antibody-based

profiling to generate protein profiles from screening serum

or plasma . Differential profiles of potential biomarker

candidates were observed and are being verified in different

assays and technologies .


• 37,000 antibodies validated (by protein arrays) from

the HPA project

• 37,000 antigens (MS verified) from the HPA project

• Whole proteome peptide arrays

• 2x EVO150 liquid-handling robot – Tecan

• SELMA 96-fold pipettor – CyBio

• LX200, MagPIX, FlexMap3D – Luminex

• Marathon inkjet microarrayer – ArrayJet

• Nanoplotter 2 .0E non-contact microarrayer – GeSim

• LuxScan HT 24 microarray scanner – CapitalBio

• G2565BA 48 slide microarray scanner – Agilent

• EL406 plate washer – Biotek

Achievements 2012

• > 10,000 antibodies in profiling of cancer and cardio-

vascular disease

• > 10,000 antigens in autoimmunity profiling within

multiple sclerosis

• Whole peptide arrays in autoimmunity profiling and

epitope mapping

• 7 peer reviewed publications

• > 20 national collaborative projects ongoing

• 1 service project initiated

Contact

Facility Manager: Assoc. Prof. Jochen M Schwenk


Phone: +46 8 524 81482

Platform Director: Prof. Peter Nilsson


Phone: +46 8 524 81418

Biobank Profiling



• A PerkinElmer 3 arm Janus robotic liquid dispensing

system with 96 and 384 head

• An ECHO550 non-contact (tip less) liquid dispenser 96 to

1536 plate format

• Two human genome wide siRNA libraries (Dharmacon

and Ambion)

• Small molecule libraries (130K compounds)

• Cell cultivation laboratory

Selected Achievements 2012

• Identification through a genomic wide RNAi knockout

screen of a number of putative genes involved in Wnt-3

mediated signaling

• Identification putative systemic lethal genes through RNAi

knockout

• Kinase siRNA screen using the Surefire technology

• Network mapping of EGFR pathway through knockout

with selected siRNA screen and substance

• Identification of a number of novel chemical entities (hits)

in 7 different chemical screens

• Transfer and solid RNAi transfection and use in antibody

validation

Contact

Facility Manager: Dr. Bo Lundgren


[email protected]

Phone: +46 8 524 81470


Facility Manager: Dr . Bo Lundgren

Mission

• To provide high-throughput RNAi knockout technology

to the Swedish research community

• To provide expertise in setting up high-throughput

microplate-based biological screening methods using

controlled and validated technology


The RNAi Cell screening facility provides high throughput

RNAi-based screenings both as customized screens using a

number of selected sets of siRNAs as well as whole genome

wide screens . The facility is equipped with state-of-the-art

instrumentation, designated cell and robotic laboratories

and highly trained personal . The facility provides expertise

and technical support to the researcher on:

• Strategies for the experimental design

• Development of endpoint assay and help on statistical

analyses of the screening data

• Setup of the robotics and carrying out the high-

throughput screen in collaboration with the researcher

The experimental work is performed in a validated and

controlled technical environment . We also provide expertise

on in vitro toxicity, cell culture or pre-clinical issues .

Cell Screening



Facility Manager: Dr . Dorothea Rutishauser

Mission

• To provide label-free quantitative proteomics analysis

using nLC/MS and low sample consumption (<1µg)

• To provide accurate mass determination (<2ppm)

• To provide de novo sequencing of polypeptides using

fragmentation methods CID, HCD and ETD

• To provide analysis of post-translational modification

• To provide bioinformatics analysis of MS data, including

quantitative Pathway Analysis

• To offer consultation on experimental design, sample

handling and MS data interpretation


The advanced proteomics facility provides fee-for-service

analysis of a big variety of protein and peptide samples

including identification, quantitation and analysis of

post-translational modifications . The facility also supports

project planning, experimental design and development of

sample preparation procedures . The main focus of the

facility is the generation of comprehensive quantitative

proteomics data sets based on recently developed methods

in high-resolution mass spectrometry-based proteomics .


• 2 Q Exactive mass spectrometers, Thermo Scientific

• LTQ Orbitrap Velos Pro ETD, Thermo Scientific

• LTQ Orbitrap XL ETD, Thermo Scientific

• Xevo TQ, Waters

• Robotics and ionization sources: Mulitprobe II; Perkin-

Elmer, TriVersa NanoMate; Advion, AP/Maldi; MassTech

Achievements 2012

• 46 new proteomics projects started

• Collaborator in two high-throughput interdisciplinary

metabolomics/proteomics projects

• In-house development of accurate label-free

quantification software

• Acquisition of AP/MALDI-source for high-resolution

MS systems

• Installation of one additional high-resolution

MS instrument including nano and normal flow

LC systems for metabolomics and proteomics projects

Contact

Facility Manager: Dr. Dorothea Rutishauser


Phone: +46 8 524 87707

Advanced Proteomics



The facility is equipped with the latest peptide separation

techniques and mass spectrometers with complementary

characteristics .

• MS LTQ Orbitrap Velos Pro, Thermo Scientific

• MS Orbitrap Q Exactive, Thermo Scientific

• Q-TOF 6540, Agilent

• 2xLC-Triple Q-MS (6410, 6490), Agilent

• MALDI-TOF/TOF, Applied Biosystems

• 6xUPLC/HPLC, Agilent

• EIF elution robotics, GE Healthcare

Achievements 2012

• 41 projects completed or ongoing

• Numerous cross platform projects initiated

• Several novel proteomics methods, experimental and

bioinformatics have been developed and published in

leading proteomics journals

• Data has been provided to many customers’ publications

in high ranked journals (MBIO, EMBO journal, JCB, MCP)

and as support to a number of grant applications

Contact

Facility Manager: Assoc. Prof. Janne Lehtiö


Phone: +46 8 524 81416


Facility Manager: Assoc . Prof . Janne Lehtiö

Mission

• To offer state-of-the-art technologies, education and

competence in proteomics for a wide range of applied

projects to elucidate biology and discover biomarkers

• To provide comprehensive proteome analysis to support

annotation of protein coding genomes, so called

proteogenomics


The Clinical proteomics facility provides services to obtain

comprehensive quantitative proteomics data, data analysis

and high quality project support for scientifically sound

projects within systems biology and biomarker discovery .

We offer fee-for-service sample analysis, support to plan

and perform larger in-depth proteomics projects, e .g .

protein identification, post-translational modification

analysis and protein quantification in complex biological

mixtures . The unit provides expertise on mass spectrometry-

based proteomics, data handling and develops methods for

improved proteome analysis .

Clinical Proteomics


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• 2x MetaSystems fully automated slide scanning micro-

scopes with integrated classifier based on the fly image

analysis and stitching software

• Leica Bond RX autostainer (IHC and ISH)

• Multichannel western blot setup and image acquisition

(Bio-Rad Chemidoc)

Achievements 2012

• Generated >100 detailed maps of protein distribution in

the mouse brain each comprising of 30 images of brain

sections with a resolution of 500 megapixels showing

both regional and cellular distribution of proteins in the

brain

• Initiated >20 collaborative projects involving analyses of

protein expression and distribution in rodent and human

tissue samples . Diseases studied in these collaborative

projects include; Alzheimer’s disease, multiple sclerosis,

stroke, Huntington’s disease, Parkinson’s disease, cancer

and hypertension

Contact

Facility Manager: Dr. Jan Mulder


Phone: +46 8 524 81421


Facility Manager: Dr . Jan Mulder

Mission

• To provide a tissue profiling platform based on multiplex

fluorescence immunohistochemistry for the analysis of

regional and cellular distribution of proteins and their

co-existence with known cellular or pathological markers

• To create a publically accessible protein atlas of the mouse

brain utilizing the unique antibody library generated

within the Human protein atlas project

• To create image analysis pipelines based on existing image

analysis tools (ImageJ, Matlab, Cell profiler)


We have generated an infrastructure optimised for the

large-scale visualisation of protein expression and distribu-

tion in the mouse brain (Protein atlas of the mouse brain) .

This infrastructure is available for collaborative service

projects that benefit from the available know-how on tissue

processing and multiplex staining procedures, automated

IHC or ISH or automated slide scanning microscopy .

Tissue Profiling



Facility Manager: Dr . Annika Jenmalm Jensen

Mission

To provide expertise and infrastructure for the development

of chemical probes to Swedish research groups with the

goal to strengthen research within chemical biology

nationally and contribute to make Swedish research in this

area internationally competitive .


Chemical Biology Consortium Sweden (CBCS) was estab-

lished in 2010 as a non-profit strategic infrastructure for

academic researchers across Sweden . CBCS is funded by

the Swedish Research Council, Karolinska Institutet and

SciLifeLab Stockholm . The organization coordinates, and

makes available, a powerful academic framework of

platforms for the discovery, development and utilization of

small-molecule probes for life-science applications . CBCS

provides expertise within assay development, computational

chemistry, cheminformatics, chemical library screening and

development, medicinal/enabling chemistry, target

identification and preclinical profiling .

CBCS can currently assist with the following techniques

and tools:

• Computational chemistry and modeling

• Assay development

• Screening of small-molecule libraries towards isolated

targets or cell lines

• Screening hit evaluation and confirmation

• Hit-to-probe optimisation

• Medicinal chemistry expertise

• In silico and in vitro Pharmacokinteics (ADME)

Infrastructure

CBCS has a state of the art infrastructure for assay develop-

ment, small-molecule screening, chemistry optimization of

hits and in silico and in vitro assays for ADMET (absorption,

distribution, metabolism, excretion, toxicity) predictions .

Achievements

Since CBCS activities started in 2010:

• More than 30 primary screens have been completed

• 3 in vivo proof-of-principle studies

• 13 publications

• 8 manuscripts in preparation

Contact

Facility Manager: Dr. Annika Jenmalm Jensen

Consortium Director, CBCS


Phone: +46 8 524 80879

www.cbcs.se

Chemical Biology


Chemical Biology

In addition to the standard services PSF also provide

guidance in protein related issues and can take on minor

protein production related tasks in parallel to the standard

process .


• Standard equipment for molecular biology and protein

production

• Instrumentation for protein crystallization and

characterization

Achievements 2012

• Performed protein production work for 31 different

research groups

• Performed 325 high-throughput purifications and

prepared > 700 expression plasmids

• Settled the working mode of the core facility and updated

methodologies

Contact

Facility Manager: Assoc. Prof. Helena Berglund


Phone: +46 8 524 86 843

www.psf.ki.se


Facility Manager: Assoc . Prof . Helena Berglund

Mission

• To provide high quality, high-throughput protein

production services

• To provide expertise in protein production, protein

characterization, and protein chemistry


The protein production platform is part of the Protein

Science Facility (PSF) established in 2011 to provide the

scientific community with protein production services and

instrumentation for protein crystallization and biophysical

characterization . PSF is based on the methodology platforms

of the Structural Genomics Consortium hosted by Karolinska

Institutet 2005–2011 and joined SciLifeLab Stockholm in

2012 .

The set up is based on high-throughput methods for

production of His-tagged proteins produced in E. coli and

standard services include:

• High-throughput sub-cloning into various expression

vectors

• Small scale expression and solubility screening

• Lab-scale production cultures

• Two-step protein purification

• Proteolytic His-tag removal

• Documentation and quality measures accompany all

delivered results and materials

Protein Production



Facility Manager: Assoc . Prof . Hans Blom

Mission

• To develop and implement new bioimaging technology

• To provide access to unique bioimaging instrumentation

• To provide expertise in bioimaging

• To support and educate bioimaging users


The mission of the Advanced Light Microscopy (ALM) facility

is to provide scientists all over Sweden with open access to

state-of-the-art superresolution fluorescence microscopy for

nanoscale biological visualisation . The ALM facility provides

access to all superresolution modalities, including the STED,

PALM, SIM, and STORM technologies developed in the last

decade . Collaborative project management and transfer of

knowledge to individual researchers are supported,

including organization of workshops and courses in

superresolution microscopy .

Via the Swedish Bioimaging Network, the ALM facility is

coordinated as a superresolution bioimaging node on a

national level . In addition to being selected a national node

for superresolution microscopy, the ALM facility has during

2012 been an advanced bioimaging node in Europe via the

large ESFRI infrastructure project Euro-Bioimaging . Together

with the University of Turku in Finland we have implemented

routines for providing access to advanced bioimaging

equipment and superresolution expertise to north European

scientist .


• Pulsed STED superresolution microscope

(~70 nm resolution in 1–2 channels)

• Gated CW-STED superresolution microscope

(~50–60 nm resolution in 1–2 channels)

• Gated dual-color Easy-STED superresolution microscope

(in-house development by Dr . Matthias Reuss)

• SIM superresolution microscope

(doubled resolution in all direction; four colors)

• PALM superresolution microscope


• dSTORM superresolution microscope


Achievements 2012

• Installation of commercial ELYRA superresolution system

from Carl Zeiss

• Host for the second superresolution user-club workshop,

co-organized with Leica Microsystems

• Over 20 national and international supported super-

resolution fluorescence microscopy projects

• Euro-Bioimaging superresolution proof-of-concept site

Contact

Facility Manager: Assoc. Prof. Hans Blom


Phone: +46 8 524 81214

www.scilifelab.se/index.php?content=bioimaging

Advanced Light Microscopy (ALM)

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Facility Manager: Dr . Jianping Liu

Mission

• To provide access to unparalleled automated and

high-throughput equipment, reagents, expertise and

training in the field of systems biology, functional

genomics and drug discovery to the scientific community


KHTC is home to one of the most sophisticated, state-of-

the-art analytical platforms in Europe . We can perform

large-scale functional genomics (cDNA and RNAi) and

compound screens in various cellular and biochemical

assays . We provide a number of high-capacity technologies

to analyse protein-protein and protein-DNA interactions as

well as next generation sequencing technology . KHTC

operates as a self-service facility where we assist with assay

development, automation and operation .


• Highly integrated laboratory automation workstations and

advanced liquid handling robots

• Fully automated microscope, Acumen eX3 High Content

Imaging System and multilabel plate reader

• Illumina HiSeq2000 DNA sequencers

• High-throughput PCR instrument and a platform for

systematic evolution of ligands by exponential enrichment

(SELEX)

• Recombinant DNA cloning/colony picking platform and

high-throughput yeast replicator

• Collections of genome-wide siRNA and ORF libraries as

well as several comprehensive chemical compound

libraries

Achievements 2012

• Successful integration of the Acumen eX3 High Content

Imaging System

• Two compound screens were completed using functional

cellular assays

• 352 sequencing runs were completed

• RNA extraction protocol for RNA sequencing was

automated

• Three siRNA pre-screens are in progress

• Four siRNA screens, one cDNA screen and three

compound screens have been initiated

• Data generated at KHTC was used in four high impact

journal publications

Contact

Facility Managers: Dr. Anders Eriksson and

Dr. Jianping Liu

E-mail: [email protected] or [email protected]

Phone: +46 8 5858 66 58

Karolinska High Throughput Center (KHTC)


Achievements 2012

• Consultancy and infrastructure support in over

200 projects nation-wide

• Development of large-scale storage for NGS analyses in

collaboration with SNIC/UPPMAX

• Development of national mass-spectrometry proteomics

data storage

• Deployment of Fido – a robust web services framework for

providing bioinformatics tools – in collaboration with

SNIC/NSC

• Set up routines for data publishing

• Planning for Swedish ELIXIR node

Contact

BILS Director: Bengt Persson


Support: [email protected] and http://biosupport.se

www.bils.se


Mission

• To provide bioinformatics infrastructure and support for

life science researchers in Sweden

• To be the national contact point towards the new

European infrastructure for biological information, ELIXIR,

and related international collaborations


BILS (Bioinformatics Infrastructure for Life Sciences) is a

distributed national research infrastructure with support

from the Swedish Research Council . BILS provides infrastruc-

ture to facilitate bioinformatics analyses including necessary

computational and storage resources (which are provided in

close collaboration with the Swedish Infrastructure for

Computing, SNIC) . Furthermore, BILS provides routes for

data publishing . BILS also provides bioinformatics expertise

in a number of areas and engages in training activities in

order to inform life science researchers about the possibili-

ties of bioinformatics .

Bioinformatics Infrastructure for Life Sciences (BILS)



Through a grant from the Wallenberg foundation, SciLifeLab

Stockholm-Uppsala can now offer in-depth bioinformatics

support for projects running at SciLifeLab platforms as a

national service . The service will initially focus on genomics

sequence data analysis, including both medical and

non-medical projects . The basic ideas behind the service are:

• Any research group at a Swedish university can apply for

the service as an addition to a standard SciLifeLab project

support grant

• Granted applications will be offered help with bioinfor-

matics data analyses by experienced bioinformaticians for

at least 3 months

• The service is free of charge . One group member should

be assigned to work alongside the WABI personnel to

ensure transfer of know-how

Currently, the WABI staff consists of 10 full-time bio-

informaticians . They will be fully integrated members of

their assigned research projects during their time of service .

An important aspect of WABI is to achieve hands-on

knowledge transfer from the WABI bioinformaticians to the

applicant’s research group . It is also our intention to offer

members of the research group to spend time at SciLifeLab

to ensure an efficient learning process .

Contact

WABI-Stockholm Director: Prof. Gunnar von Heijne


The Wallenberg Advanced Bioinformatics Infrastructure (WABI)

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National Reference Committee

Prof . Bernt Eric Uhlin, Umeå University

Prof . Göran Larsson, Göteborg University

Prof . Jens Nielsen, Chalmers University

Prof . Karl-Eric Magnusson (chairman), Linköping University

Prof . Gunilla Westergren Thorsson, Lund University

Prof . Johan Schnurer, Swedish University of Agricultural Sciences

Prof . Stefan Ståhl, KTH Royal Institute of Technology

Prof . Henrik Grönberg, Karolinska Institutet

Prof . Neus Visa, Stockholm University

Prof . Bengt Westermark, Uppsala University

Annual report project team

Mikaela Friedman

Fredrik Sterky

Mathias Uhlén

Photo

Håkan Lindgren

Contact

General questions:

Fredrik Sterky, Site Director

[email protected]

Scientific communication and External relations:

Mikaela Friedman

[email protected]

Administration and personnel:

Martina Selander

[email protected]

More information:

www.scilifelab.se

Board 2012

Prof . Jan Andersson, KI (chairman)

Prof . Peter Arner, KI

Prof . Stefan Nordlund, SU

Prof . Ylva Engström, SU

Prof . Sophia Hober, KTH

Prof . Stefan Ståhl, KTH

Directors (appointed in the end of 2012)

Prof . Mathias Uhlen (KTH), Center Director

Prof . Gunnar von Heijne (SU), Vice Center Director

Prof . Jan Andersson (KI), Vice Center Director

Prof . Anna Wedell (KI), Scientific Director

Prof . Mats Nilsson (SU), Scientific Director

Prof . Helene Andersson Svahn (KTH), Scientific Director

Assoc . Prof . Fredrik Sterky, Site Director

Prof . Karin Dahlman-Wright, Site Director Huddinge

Scientific Advisory Board

Prof . Bertil Andersson, Singapore

Prof . Kai Simons, Germany

Prof . Janet Thornton, UK

Prof . Sören Brunak, Denmark

Prof . Jan Ellenberg, Germany

Prof . Svante Pääbo, Germany

Prof . Yoshihide Hayashizaki, Japan

Prof . Craig Venter, USA

Prof . Leroy Hood, USA

Prof . Richard Caprioli, USA

Prof . Stephen Friend, USA

Prof . Jonathan Knowles, Switzerland

Prof . Elaine Mardis, USA

Management of SciLifeLab Stockholm


Immunofluorescent staining of human U-2 OS osteosarcoma cells, using an antibody HPA036090 towards Tensin-1, shows positivity in focal adhesions.

SciLifeLab Stockholm has been formed jointly by the three Stockholm universities,

KTH Royal Institute of Technology, Karolinska Institutet (KI) and Stockholm University (SU),

and thus combines the profiles and strengths of these three institutions .

Read more at: www.scilifelab.se

scilifelab stockholm 2012

Documents

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