INFECTION RESEARCH TO MEET CURRENT AND FUTURE CHALLENGES A SYMPOSIUM TO CELEBRATE THE KNUT AND ALICE WALLENBERG FOUNDATION’S 100-YEAR ANNIVERSARY

June 19, 2017, Aula Nordica, Universums gränd 4, Umeå

INFECTION RESEARCH TO MEET CURRENT AND FUTURE CHALLENGES 1 KNUT AND ALICE WALLENBERG FOUNDATION 100 YEARS IN SUPPORT OF EXCELLENT SWEDISH RESEARCH AND EDUCATION

The Knut and Alice Wallenberg Foundation primarily grants funding in the natural sciences, technology and medicine, in the form of grants for basic research of the highest international standard. During the Foundation’s 100 years, SEK 24 billion has been awarded in grants for excellent Swedish research and education. Recent annual grants of SEK 1.7 billion make the Foundation one of the largest private funders of scientific research in Europe.

Over their lifetimes, Knut and Alice Wallenberg built up a sizable fortune, and, even before the establishment of the Foundation, they financed various construction and public development projects. They wanted to organize their support through the establishment of the Foundation. The endowment consisted mainly of shares in Stockholms Enskilda Bank and Investor worth SEK 20 million, SEK 593 million in today’s currency value. Even though the Foundation has granted SEK 24 billion, the assets have, after 100 years and successful capital management, grown to SEK 90 billion.

Knut and Alice Wallenberg were determined to promote scientific research and education beneficial to Sweden, things that contributed to Swedish progress in research and education. In the beginning, the Foundation mainly financed buildings to house research and education. Gradually the support shifted to financing of advanced equipment needed for research. In recent years one of the main areas of support has been individual grants for outstanding researchers. The Foundation supports outstanding individuals through its programs: Wallenberg Scholars and Wallenberg Clinical Scholars for senior scientists; and Wallenberg Academy Fellows for younger scientists. Another important area is grants for researcher-initiated projects with high scientific potential and of the highest international standard.

2 INFECTION RESEARCH TO MEET CURRENT AND FUTURE CHALLENGES KNUT AND ALICE WALLENBERG FOUNDATION INFECTION RESEARCH TO MEET CURRENT AND FUTURE CHALLENGES

Infectious diseases remain major causes of morbidity and mortality throughout the world. Scientific efforts providing better knowledge about pathogenic mechanisms can result in both innovative new research tools and new strategies for prevention and treatment. In the case of bacterial infections, there are pressing current issues regarding emerging and re-emerging infectious diseases and increasing problems with antibiotic resistance, for example. In this symposium, the invited experts will highlight approaches and examples from different areas of current research about and viruses. The scientists will also participate in a panel discussion where they will exchange ideas about how to better meet the future challenges posed by infections.

The centenary will be celebrated with the following symposia:

LUND, April 4, BIG QUESTIONS IN ASTROPHYSICS – THE NEXT DECADES UMEÅ, June 19, INFECTION RESEARCH TO MEET CURRENT AND FUTURE CHALLENGES LINKÖPING, September 13, MATERIALS AND TECHNOLOGY FOR A DIGITAL FUTURE STOCKHOLM, September 15, MOLECULAR LIFE SCIENCE UPPSALA, September 21, HUMAN PROGRESS IN THE 21ST CENTURY – BRIGHT AND DARK SIDES OF DEMOCRATIZATION

GOTHENBURG, September 28, METABOLISM – THE FOUNDATION OF LIFE

For more information, visit our website http://kva.se/sv/kalendarium

INFECTION RESEARCH TO MEET CURRENT AND FUTURE CHALLENGES 3 KNUT AND ALICE WALLENBERG FOUNDATION PROGRAM

INFECTION RESEARCH TO MEET CURRENT AND FUTURE CHALLENGES A SYMPOSIUM TO CELEBRATE THE KNUT AND ALICE WALLENBERG FOUNDATION’S 100-YEAR ANNIVERSARY

Monday, June 19, 2017, Aula Nordica, Universums gränd 4, Umeå

09:30–09:35 INTRODUCTION Bernt Eric Uhlin, Chairman of the Program Committee

09:35–09:40 WELCOME REMARKS Hans Adolfsson, Vice-Chancellor, Umeå University and Peter Högberg, Vice-Chancellor, Swedish University of Agricultural Sciences

09:40–09:55 PRESENTATION OF THE KNUT AND ALICE WALLENBERG FOUNDATION Peter Wallenberg Jr and Göran Sandberg, the Knut and Alice Wallenberg Foundation

09:55–10:00 THE ROYAL SWEDISH ACADEMY OF SCIENCES Göran K. Hansson, Secretary General, the Royal Swedish Academy of Sciences

SESSION 1 Chairs: Sun Nyunt Wai, Umeå University & Hans Wolf-Watz, Umeå University

10:00–10:35 PATHOGENS, COMMENSALS AND THE HOST MUCOSAL SURFACE: THE DISCREET CHARM OF THE «MÉNAGE À TROIS» Philippe Sansonetti, Institut Pasteur, Paris, France

10:35–11:10 BACTERIAL QUORUM SENSING AND ITS CONTROL Bonnie Bassler, , New Jersey, USA

11:10 –11:45 THE ROLE OF DNA DAMAGE IN INNATE IMMUNITY Nelson O. Gekara, Umeå University, Sweden

4 INFECTION RESEARCH TO MEET CURRENT AND FUTURE CHALLENGES KNUT AND ALICE WALLENBERG FOUNDATION 11:45 –13:00 LUNCH + POSTERS

SESSION 2 Chairs: Birgitta Henriques-Normark, Karolinska Institutet & Sven Bergström, Umeå University

13:00–13:35 LEPROSY – ZOONOSIS AND ANTHROPONOSIS Stewart Cole, École Polytechnique Fédérale de Lausanne, Switzerland

13:35–14:10 EXPANDING BACTERIAL SIGNALING VOCABULARY FROM INFLAMMATION TO NEUROPROLIFERATION AND BRAIN REPAIR Elaine Tuomanen, St. Jude Children’s Research Hospital, Memphis, USA

14:10–14:45 UTI COMPLEXITY DEFINED BY A DIVERSE BACTERIAL-HOST INTERFACE Scott Hultgren, Washington University School of Medicine, St Louis, USA

14:45–15:15 COFFEE + POSTERS

SESSION 3 Chairs: Maria Fällman, Umeå University & Bernt Eric Uhlin, Umeå University

15:15–15:50 IDENTIFICATION OF VIRAL ACHILLES’ HEELS DURING FLAVIVIRUS INFECTION Peter Sarnow, Stanford University School of Medicine, USA

15:50–16:25 CRISPR-CAS9: A BACTERIAL IMMUNE SYSTEM REPURPOSED AS A TRANSFORMATIVE GENOME ENGINEERING TECHNOLOGY Emmanuelle Charpentier, Max Planck Institute for Infection Biology, Berlin, Germany

16:25–17:10 PANEL DISCUSSION WITH SPEAKERS Introduction: Staffan Normark, Karolinska Institutet

17:10–17:20 CLOSING REMARKS Hans Wolf-Watz, Umeå University

17:20–18:30 POSTERS + REFRESHMENTS

INFECTION RESEARCH TO MEET CURRENT AND FUTURE CHALLENGES 5 KNUT AND ALICE WALLENBERG FOUNDATION PHOTO: MAGNUS BERGSTRÖM MAGNUS PHOTO:

6 INFECTION RESEARCH TO MEET CURRENT AND FUTURE CHALLENGES KNUT AND ALICE WALLENBERG FOUNDATION PHOTO: INSTITUT PASTEUR’S SERVICE PASTEUR’S INSTITUT PHOTO:

PATHOGENS, COMMENSALS AND HOST MUCOSAL SURFACE: A STORMY « MÉNAGE À TROIS » Philippe Sansonetti, Institut Pasteur, Paris, France

Among its multiple roles, the gut microbiota exerts a function of potent barrier to incoming bacteria, hence, any bacterial pathogen poised to colonize the mucosal surface needs to compete with it. Shigella sonnei is no exception to this rule. Following development of a Guinea pig model of colonic infection, we showed that S. sonnei has evolved a specific colonization capacity to the expense of the microbiota.

Expression of a functional Type 6 Secretory System (T6SS) is essential for colon colonization by S. sonnei. S. sonnei newcomers proceed to restricted niche substitution, engaging with commensal E. coli that occupy epithelial vicinity.

PHILIPPE SANSONETTI is Professor at the Collège de France (Chaire de Microbiologie et Maladies Infectieuses) and Distinguished Professor at the Institut Pasteur where he directs the Molecular Microbial Pathogenesis Unit and INSERM Unit 1202.

Following his M.D. degree in 1979 and his postdoctoral research at the Walter Reed Army Institute of Research in the USA, he began to work at Institut Pasteur. His research concerns the genetic molecular and cellular bases of bacterial pathogenesis with Shigella as primary model, as well as the mechanisms of gut homeostasis and pathology in the presence of symbiotic bacteria. With his team, he has developed candidate vaccines against in shigellosis.

INFECTION RESEARCH TO MEET CURRENT AND FUTURE CHALLENGES 7 KNUT AND ALICE WALLENBERG FOUNDATION PHOTO: ALENA SOBOLEVA

BACTERIAL QUORUM SENSING AND ITS CONTROL Bonnie Bassler, Princeton University, New Jersey, USA

Bacteria are tiny ancient organisms. Harmful bacteria can kill humans, animals, and plants, while beneficial bacteria play vital roles in keeping humans, animals, and plants alive. How do accomplish these feats given that they are so small? They communicate with small molecules, count their numbers, and act as collectives. This process is called “quorum sensing” and it allows bacteria to synchronize behavior on a population-wide scale. Quorum sensing controls virulence, biofilm formation, and the exchange of DNA. Biomedical research aims to develop therapies to manipulate quorum sensing to combat bacterial pathogenicity and to promote beneficial bacterial behaviors.

BONNIE BASSLER Bonnie Bassler is a Howard Hughes Medical Institute Investigator and the Squibb Professor and Chair of the Department of at Princeton University. Bassler received a B.S. in from the University of California at Davis, and a Ph.D. in Biochemistry from the . She performed postdoctoral work in Genetics at the Agouron Institute.

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THE ROLE OF DNA DAMAGE IN INNATE IMMUNITY Nelson O. Gekara, Umeå University, Sweden

Innate immunity – the ability to sense and rapidly respond to danger, requires tight control to avert self-destruction. My lab is interested in the mechanisms that govern the regulation of the immune system and how the breakdown of such mechanisms culminate in disease. DNA damage is a constant threat to all life forms. Recently, we showed that DNA damage has a major role in immune regulation and have discovered that several regulatory proteins at the intersections of DNA damage response and the innate immune system. Here I will provide an overview of recent findings on the mechanisms of DNA damage in innate immunity and its impact on infections, inflammatory diseases and cancer.

NELSON O. GEKARA grew up and studied Biochemistry in Kenya. He worked at the International Livestock Research Institute – Nairobi then at the Institute of Animal Pathology, Bern, Switzerland. 2001-2010, he did his Ph.D and subsequent postdoctoral research at the Helmholtz Centre for Infection Research and the University of Cologne, Germany. In 2010, the MIMS - Umeå University as a principle investigator.

INFECTION RESEARCH TO MEET CURRENT AND FUTURE CHALLENGES 9 KNUT AND ALICE WALLENBERG FOUNDATION PHOTO: HERZOG ALAIN

LEPROSY – ZOONOSIS AND ANTHROPONOSIS Stewart Cole, École Polytechnique Fédérale de Lausanne, Switzerland

Genomics revolutionized our understanding of the unculturable human pathogen, Mycobacterium leprae, and underpins phylogeographic investigations. Leprosy is believed to result solely from inter-human transmission. In the USA, M. leprae is endemic in wild armadillos and the strain has the European genotype indicating likely anthroponotic origin. Autochtonous cases of human leprosy occur in areas where armadillos are endemic indicating zoonotic transmission. In the UK, red squirrels are naturally infected with M. leprae, or the related M. lepromatosis, indicating another possible environmental reservoir. A one-world, one-health approach to leprosy control is both necessary and required.

STEWART COLE is an international authority in mycobacteriology thanks to his studies on multidrug- resistant tuberculosis and his pioneering work on the pathogenicity, evolution and genomics of the tubercle and leprosy bacilli. He is currently engaged in discovering new drugs to treat tuberculosis and in unravelling the epidemiology of leprosy.

10 INFECTION RESEARCH TO MEET CURRENT AND FUTURE CHALLENGES KNUT AND ALICE WALLENBERG FOUNDATION ST JUDE CHILDREN’S RESEARCH HOSPITAL RESEARCH CHILDREN’S JUDE ST PHOTO: THE BIOMEDICAL COMMUNICATIONS DIVISION OF

EXPANDING BACTERIAL SIGNALING VOCABULARY FROM INFLAMMATION TO NEUROPROLIFERATION AND BRAIN REPAIR Elaine Tuomanen, St. Jude Children’s Research Hospital,

Memphis, USA

Host bacterial interactions have traditionally been viewed as a war zone where bacterial PAMPs send the alarm, innate immunity responds and hopefully the host survives the carnage. New studies show host-bacterial two-way conversations also occur at a whisper in the absence of overt disease. Two examples will be discussed. Antimicrobial peptides signal a novel autolysin pathway of bacterial resurfacing without death. The bacterial cell wall-TLR2 signaling axis silently affects fetal neurodevelopment and may contribute to postnatal cognitive disorders. These examples expand classical host bacterial entanglements from inflammation to a new level of subtlety with wide ranging consequences.

ELAINE I. TUOMANEN, M.D. Dr. Tuomanen is Chair of Infectious Diseases at St. Jude Children’s Research Hospital. She is an infectious diseases clinician with 3 decades of award winning basic research on the pathogenesis of pneumococcal disease. She studies how pneumococci interact with the innate immune response and has developed therapies to alleviate brain damage in meningitis and a protein based pneumococcal vaccine.

INFECTION RESEARCH TO MEET CURRENT AND FUTURE CHALLENGES 11 KNUT AND ALICE WALLENBERG FOUNDATION PHOTO: WASHINGTON UNIVERSITY ST. LOUIS UNIVERSITY WASHINGTON PHOTO:

UTI COMPLEXITY DEFINED BY A DIVERSE BACTERIAL-HOST INTERFACE Scott Hultgren, Washington University School of Medicine, St Louis, USA

Hultgren is a world-leader in microbial pathogenesis, combining basic and clinical research to conduct pioneering studies on chaperone/usher pathway pili and urinary tract infections (UTI) in women. He has provided new insights into acute and recurrent UTI and translated his work into novel clinical approaches for the treatment and prevention of UTI by developing anti-adhesive mannosides that specifically block E. coli colonization of the lower urinary tract, pilicides that inhibit the assembly of a broad class of bacterial adhesins, and adhesin-based vaccines for the prevention of UTI. Hultgren’s leadership in women’s health research has had a major national and international impact.

SCOTT HULTGREN. Elected National Academy of Sciences. Received Eli Lilly Award. Member of NIH UKGD Study Section; AUA Research Council; NIH ORWH Advisory Committee; NIH Mucosal Immunology Studies Team; Second Century Award; Scientific Advisory Boards: BWF Consortium on Preterm Birth, Genentech, MedImmune, Sequoia, and Roche. Founder Fimbrion Therapeutics and QureTech Bio.

12 INFECTION RESEARCH TO MEET CURRENT AND FUTURE CHALLENGES KNUT AND ALICE WALLENBERG FOUNDATION SCHOOL OF MEDICINE PHOTO: COURTESY OF STANFORD UNIVERSITY,

IDENTIFICATION OF VIRAL ACHILLES’ HEELS DURING FLAVIVIRUS INFECTION Peter Sarnow, Stanford University School of Medicine, USA

MicroRNAs interact with nucleotide sequences sites that reside in 3’ noncoding regions in target mRNAs, leading to posttranscriptional downregulation of mRNA expression. In contrast, liver-specific microRNA miR-122 binds to the 5’ end of the hepatitis C virus (HCV) RNA genome, resulting in upregulation of viral RNA abundance. Extensive analyses have shown that miR-122 regulates the turnover of HCV RNA by protection against nucleases. Clinical trials showed that single subcutaneous injections of small RNAs, with base complementarity to miR-122, resulted in loss of HCV in infected patients. Thus, anti-sense miR-122 RNA treatment is a powerful therapeutic approach against HCV.

DR. PETER SARNOW received his Ph.D. from Stony Brook University in New York under the guidance of Dr. Arnold Levine. Subsequently, he performed a postdoctoral fellowship with Dr. David Baltimore at the MIT/Whitehead Institute in Boston. He is currently Professor and Chair of the Department of Microbiology and Immunology at Stanford University. His research focuses on the pathogenesis of RNA viruses.

INFECTION RESEARCH TO MEET CURRENT AND FUTURE CHALLENGES 13 KNUT AND ALICE WALLENBERG FOUNDATION PHOTO: HALLBAUER & FIORETTI HALLBAUER PHOTO:

CRISPR-CAS9: A BACTERIAL IMMUNE SYSTEM REPURPOSED AS A TRANSFORMATIVE GENOME ENGINEERING TECHNOLOGY Emmanuelle Charpentier, Max Planck Institute for Infection Biology, Berlin, Germany

The RNA-programmable CRISPR-Cas9 system has recently emerged as a transformative technology in biological sciences, allowing rapid and efficient targeted genome editing, chromosomal marking and gene regulation in a large variety of cells and organisms, including human cells, plants and mice. In this system, the endonuclease Cas9 or catalytically inactive Cas9 variants are programmed with single guide RNAs (sgRNAs) to target site-specifically any DNA sequence of interest given the presence of a short sequence (Protospacer Adjacent Motif, PAM) juxtaposed to the complementary region between the sgRNA and the target DNA. The system is efficient, versatile and easily programmable.

Originally CRISPR-Cas9 is an RNA-mediated adaptive immune system in bacteria. I will discuss the biological functions, mechanisms, evolution and applications of CRISPR-Cas9 as a novel genome engineering technology, and present details of a recently identified new type of bacterial immunity, the CRISPR-Cpf1 system.

EMMANUELLE CHARPENTIER. Max Planck Institute for Infection Biology, Department of Regulation in Infection Biology, D-10117 Berlin, Germany; The Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå Centre for Microbial Research (UCMR), Department of Molecular Biology, Umeå University, S-90187 Umeå, Sweden; Humboldt University, D-10099 Berlin, Germany

14 INFECTION RESEARCH TO MEET CURRENT AND FUTURE CHALLENGES KNUT AND ALICE WALLENBERG FOUNDATION PHOTO: MAGNUS BERGSTRÖM MAGNUS PHOTO:

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16 INFECTION RESEARCH TO MEET CURRENT AND FUTURE CHALLENGES KNUT AND ALICE WALLENBERG FOUNDATION KNUT AND ALICE WALLENBERG FOUNDATION

The Knut and Alice Wallenberg Foundation was established in 1917. The Foundation’s aim is to benefit Sweden by supporting Swedish basic research and education, mainly in medicine, technology and the natural sciences. This is achieved through grants to excellent researchers and to projects.

During the Foundation’s 100 years SEK 24 billion has been awarded in grants for excellent research and education, of which SEK 1.7 billion annually in recent years, making the Foundation one of the largest private funders of scientific research in Europe.

THE ROYAL SWEDISH ACADEMY OF SCIENCES

The Royal Swedish Academy of Sciences is an independent, non-governmental organisation with a charter that, in its first article, defines its function as promoting the sciences and strengthening their influence in society. The Academy promotes science of the highest quality by fostering development and innovation in Swedish research. It enhances the status of science in society by drawing attention to key social issues, examining them in scientific terms and communicating the results, and joins in cooperation on global issues, with the aim of being an international scientific proponent of sustainable development.

INFECTION RESEARCH TO MEET CURRENT AND FUTURE CHALLENGES 17 KNUT AND ALICE WALLENBERG FOUNDATION PHOTO: MAGNUS BERGSTRÖM MAGNUS PHOTO:

INFECTION RESEARCH TO MEET CURRENT AND FUTURE CHALLENGES

18 INFECTION RESEARCH TO MEET CURRENT AND FUTURE CHALLENGES KNUT AND ALICE WALLENBERG FOUNDATION