{"id":22435,"date":"2019-07-11T12:25:26","date_gmt":"2019-07-11T10:25:26","guid":{"rendered":"https:\/\/irb.usi.ch\/?page_id=22435"},"modified":"2023-01-26T11:55:20","modified_gmt":"2023-01-26T09:55:20","slug":"reti-di-ricerca","status":"publish","type":"page","link":"https:\/\/irb.usi.ch\/it\/reti-di-ricerca\/","title":{"rendered":"Reti di ricerca"},"content":{"rendered":"\t\t
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Reti di ricerca<\/p>\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t

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\n\t\t\t\n\t\t\t\t\t\t<\/span>\n\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t
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\n\t\t\t\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<\/i><\/span>\n\t\t\t\t\t\t\t\t<\/i><\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t2020-2022: ATAC - Antibody therapy against coronavirus (COVID-19)<\/a>\n\t\t\t\t\t<\/div>\n\t\t\t\t\t
Hosting organisation:<\/b><\/td>

Karolinska Institutet, Sweden<\/p><\/td><\/tr>

Coordinator:<\/b><\/td>Qiang Pan Hammarstr\u00f6m,<\/td><\/tr>
IRB Participants:<\/b><\/td>

Davide Robbiani<\/a>, Director<\/p>

Luca Varani<\/a>, Group Leader<\/p><\/td><\/tr>

Partners:<\/b><\/td>

Karolinska Institutet, Sweden<\/p>

JRC-Joint Research Centre-European Commission, Belgium<\/p>

Technische Universit\u00e4t Braunzchweig, Germany<\/p>

Fondazione IRCCS Policlinico San Matteo, Italy<\/p><\/td><\/tr>

Research area:<\/b><\/td>

EU – Horizon 2020 – SC1-PHE-CORONAVIRUS-2020<\/p><\/td><\/tr>

Duration:<\/b><\/td>01.04.2020<\/span>\u00a0to\u00a031.03.2022<\/span><\/span><\/td><\/tr>
Website:<\/b><\/td>http:\/\/www.covidantibody.eu<\/a><\/td><\/tr><\/tbody><\/table><\/section>

ATAC aims at developing passive immunotherapy against COVID-19. Human antibodies will be obtained from blood of CoV-recovered donors from China and Italy with three independent approaches: polyclonal gamma-globulins, B cell monoclonals and phage libraries. Antibodies will be characterized by rapid experimental and computational work, optimized, produced and tested in consultation with EMA to ensure prompt embedding of regulatory aspects.<\/p>

The partners have outstanding experience in all aspects of the project, collaborated previously and worked on antibody therapy for diseases including SARS and MERS-CoV. Reagents and experienced personnel are already available ensuring quick and efficient progress, with initial deliverables within 3 months.<\/p>

Besides providing a lead human antibody candidate for therapy, ATAC will rapidly disseminate results to help respond to the current COVID-19 epidemic. Results of the 2 years project will also further our understanding of CoV neutralization, contributing to future vaccination and therapeutic strategies.<\/p>

The team includes the Karolinska Institutet (SE, Pan-Hammarstr\u00f6m and Hammarstr\u00f6m, coordinators), the Institute for Research in Biomedicine (CH, Varani and Robbiani); the Joint Research Centre- European Commission (BE, Calzolai); Technische Universit\u00e4t Braunschweig (DE, Hust) and Policlinico San Matteo (IT, Baldanti). The partners\u2019 outstanding expertise is attested by high impact publications on antibody treatment for emerging infectious diseases.<\/p><\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t\t\t

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\n\t\t\t\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<\/i><\/span>\n\t\t\t\t\t\t\t\t<\/i><\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t2017-2022: RTCure - Rheuma Tolerance for Cure<\/a>\n\t\t\t\t\t<\/div>\n\t\t\t\t\t
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Hosting organisation:<\/b><\/td>\n\n

Karolinska Institutet<\/p>\n<\/td>\n<\/tr>\n

Coordinator:<\/b><\/td>\nLars Klareskog<\/td>\n<\/tr>\n
IRB Participants:<\/b><\/td>\n\n

Federica Sallusto<\/a>, Group Leader<\/p>\n<\/td>\n<\/tr>\n

Research area:<\/b><\/td>\n\n

Innovative Medicine Initiative<\/p>\n<\/td>\n<\/tr>\n

Duration:<\/b><\/td>\n01.09.2017<\/span> to 31.08.2022<\/span><\/span><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<\/section>\n

In line with IMI2 goals for improved therapies and precision medicine, the aim of this proposal is to prevent and treat RA or its progression by inhibiting maturation\/expansion of pathogenic autoimmune responses through immune tolerising treatments of subjects not only in early stages of joint inflammation (undifferentiated arthritis and early RA) but also in even earlier defined stages i.e. before onset of joint inflammation, when patients have arthralgia and\/or bone loss, or sub-clinical stages of joint inflammation.
Today, no drugs are approved for these early phases of RA development, where symptoms such as pain and fatigue cause major loss of life quality and where successful interference would prevent onset of disease. Thus, an important part of our work will be to achieve a better understanding of this as yet unexplored phase of disease. In the proposed project we will develop and validate new methods to identify individuals at high risk for RA, tools to monitor disease progress and expand and further develop cohorts suitable for these purposes.
Furthermore we will validate and standardise methods to monitor immune tolerance to be used in clinical trials for tolerising therapies for RA.
The aim is thus to interfere with the specific immune reactions that contribute to RA symptoms in such a way that a specific and long-lasting therapeutic effect (ultimately a cure) is accomplished for a major proportion of RA patients and prevention of diseases is accomplished in individuals at high risk for RA.
Investigator-initiated as well as company-sponsored clinical trials in well stratified patient groups will be performed in collaboration with SMEs and\/or contributing pharma companies and their immune effects studied using the same panel of biomarkers allowing for standardisation across protocols. Our ambition is also to disseminate our experiences from RA to other rheumatic and other immune-mediated diseases.<\/p><\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t\t\t

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\n\t\t\t\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<\/i><\/span>\n\t\t\t\t\t\t\t\t<\/i><\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t2017-2020: NCCR \u2018RNA & Disease\u2019<\/a>\n\t\t\t\t\t<\/div>\n\t\t\t\t\t
Hosting organisation:<\/b><\/td>

National Center of Competence in Research (NCCR) \u2018RNA & Disease\u2019<\/p><\/td><\/tr>

Coordinator:<\/b><\/td>Prof. Oliver M\u00fchlemann, University of Bern<\/td><\/tr>
IRB Participants:<\/b><\/td>

Silvia Monticelli<\/a>, Group Leader<\/p><\/td><\/tr>

Research area:<\/b><\/td>

RNA and disease<\/p><\/td><\/tr>

Duration:<\/b><\/td>01.09.2017<\/span>\u00a0to\u00a031.08.2020<\/span><\/span><\/td><\/tr>
Website:<\/b><\/td>http:\/\/www.nccr-rna-and-disease.ch\/tiki-index.php?page=AssociateOverview<\/a><\/td><\/tr><\/tbody><\/table><\/section>

The NCCR \u2018RNA & Disease\u2019 is a research instrument of the Swiss National Science Foundation, and is a coordinated, interdisciplinary research program aiming at identifying disease mechanisms resulting from aberrant RNA functions.<\/p>

Silvia Monticelli<\/strong>\u00a0will participate to this network with a project about the role of microRNAs (miRNAs) in the regulation of human T cell activation and functions in multiple sclerosis (MS). This project will be performed in collaboration with Prof. Jonathan Hall (ETH Zurich).<\/p>

MS is a chronic neuroinflammatory disease initiated by autoreactive T lymphocytes; however, the frequency of circulating autoreactive lymphocytes is similar between people with MS and healthy individuals and, at least in animal models, it is also comparable to the frequency of T cells specific for foreign viruses, indicating that the mere presence of such autoreactive cells is not sufficient to explain their pathogenicity. Mechanisms likely to be crucial in MS include therefore all those processes that regulate the threshold, magnitude and quality of T lymphocyte responses. Among the factors that are gaining importance in the control of T cell responses in normal and diseased conditions are miRNAs, short noncoding RNA molecules that have become clear determinants of cellular fate and responses in a wide variety of different systems. MiRNAs are now considered increasingly important in autoimmunity, and similarly to infectious diseases, for which miRNAs are already in clinical trial, they could be potentially considered as a novel therapeutic strategy. However, due to the complex interactions usually existing between miRNAs and their targets, it is essential to first dissect the effects of a given miRNA network, which is exactly the scope of this project.<\/p><\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t\t\t

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\n\t\t\t\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<\/i><\/span>\n\t\t\t\t\t\t\t\t<\/i><\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t2016-2020: EHVA - European HIV Vaccine Alliance: an EU platform for the discovery and evaluation of novel prophylactic and therapeutic vaccine candidates<\/a>\n\t\t\t\t\t<\/div>\n\t\t\t\t\t
Coordinator:<\/strong><\/td>Institut National de la Sant\u00e9 et de la Recherche Scientifique ((INSERM)<\/td><\/tr>
IRB Participants:<\/strong><\/td>

Antonio Lanzavecchia<\/a>, Director<\/p><\/td><\/tr>

Partners:<\/strong><\/td>

39 partners<\/p><\/td><\/tr>

Research area:<\/strong><\/td>

H2020-PHC-2015-single stage-RTD<\/p><\/td><\/tr>

Duration:<\/strong><\/td>01.01.2016<\/span>\u00a0to\u00a031.12.2020<\/span><\/span><\/td><\/tr><\/tbody><\/table><\/section>

Despite enormous progress in the prevention and treatment of HIV\/AIDS, the global response cannot keep pace: 35 million people are living with HIV worldwide with ca 6,000 new infections each day. Numerous HIV prevention strategies (such as PrEP and PEP), though proven successful, are difficult to sustain long-term. A vaccine still represents the most effective tool in the combat against HIV from a public health perspective. To date, many prophylactic and therapeutic vaccine concepts have been developed and several efficacy trials have been conducted but with limited success. There is an urgent need to develop better vaccines and tools predictive of immunogenicity and of correlates of protection at the early stage of vaccine development to mitigate the risks of failure.<\/p>

EHVA APPROACH<\/strong><\/p>

To address these complex and challenging scientific issues, EHVA aims to develop a Multidisciplinary Vaccine Platform through a global and innovative alliance notably:<\/p>

\u2022 Multidisciplinary expertise from vaccine discovery, to immune monitoring to clinical development<\/p>

\u2022 State-of-the-art innovative technologies to profile immune responses and virus reservoir<\/p>

\u2022 Access to large cohort studies bringing together top European clinical centres in the fields of \u00a0prophylactic and therapeutic vaccines<\/p>

\u2022 Access to a panel of experimental HIV vaccines under clinical development as benchmark<\/p>

\u2022 Liaison with African leading scientists\/programs fostering future testing of EHVA vaccines in Sub-Saharan Africa<\/p>

\u2022 Engagement of industrial expertise for downstream vaccine development<\/p>

EHVA OBJECTIVES<\/strong><\/p>

EHVA plans to develop and implement:<\/p>

\u2022\u00a0Discovery Platform\u00a0<\/strong>with the goal of generating novel vaccine candidates inducing potent neutralizing and non-neutralizing antibody responses and Tcell responses<\/p>

\u2022\u00a0Immune Profiling Platform\u00a0<\/strong>with the goal of ranking novel and existing (benchmark) vaccine candidates on the basis of the immune profile<\/p>

\u2022\u00a0Data Management\/Integration\/Down-Selection Platform<\/strong>, with the goal of\u00a0 providing statistical tools for the analysis and interpretation of complex data and algorithms for the efficient selection of vaccines<\/p>

\u2022\u00a0Clinical Trials Platform\u00a0<\/strong>with the goal of accelerating the clinical development of novel vaccines and the early prediction of vaccine failure.<\/p><\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t\t\t

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\n\t\t\t\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<\/i><\/span>\n\t\t\t\t\t\t\t\t<\/i><\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t2016-2019: ZIKAlliance - A global alliance for Zika virus control and prevention<\/a>\n\t\t\t\t\t<\/div>\n\t\t\t\t\t
Hosting organisation:<\/b><\/td>

Institut National de la Sante et de la Recherche M\u00e9dicale, Paris, France<\/p><\/td><\/tr>

Coordinator:<\/b><\/td>Prof. Xavier de Lamballerie<\/td><\/tr>
IRB Participants:<\/b><\/td>

Federica Sallusto<\/a>, Group Leader<\/p><\/td><\/tr>

Research area:<\/b><\/td>

H2020-SC1-2016-2017 SC1-PM-22-2016<\/p><\/td><\/tr>

Duration:<\/b><\/td>01.10.2016<\/span>\u00a0to\u00a030.09.2019<\/span><\/span><\/td><\/tr>
Website:<\/b><\/td>http:\/\/www.zikalliance.eu<\/a><\/td><\/tr><\/tbody><\/table>

ZIKAlliance is a multidisciplinary project with a global “One Health” approach, built: on a multi-centric network of clinical cohorts in the Caribbean, Central & South America; research sites in countries where the virus has been or is currently circulating (Africa, Asia, Polynesia) or at risk for emergence (Reunion Island); a strong network of European and Brazilian clinical & basic research institutions; and multiple interfaces with other scientific and public health programmes. ZIKAlliance will address three key objectives relating to (i) impact of Zika virus (ZIKV) infection during pregnancy and short & medium term effects on newborns, (ii) associated natural history of ZIKV infection in humans and their environment in the context of other circulating arboviruses and (iii) building the overall capacity for preparedness research for future epidemic threats in Latin America & the Caribbean. The project will take advantage of large standardised clinical cohorts of pregnant women and febrile patients in regions of Latin America and the Caribbean were the virus is circulating, expanding a pre-existing network established by the IDAMS EU project. I will also benefit of a very strong expertise in basic and environmental sciences, with access to both field work and sophisticated technological infrastructures to characterise virus replication and physiopathology mechanisms. To meet its 3 key objectives, the scientific project has been organised in 9 work packages, with WP2\/3 dedicated to clinical research (cohorts, clinical biology, epidemiology & modeling), WP3\/4 to basic research (virology & antivirals, pathophysiology & animal models), WP5\/6 to environmental research (animal reservoirs, vectors & vector control) , WP7\/8 to social sciences & communication, and WP9 to management. The broad consortium set-up allow gathering the necessary expertise for an actual interdisciplinary approach, and operating in a range of countries with contrasting ZIKV epidemiological status.<\/p><\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t\t\t

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\n\t\t\t\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<\/i><\/span>\n\t\t\t\t\t\t\t\t<\/i><\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t2015-2018: Sinergia 160719 - Interplay of classical and atypical chemokine receptors in immune cell trafficking and dynamic microarchitecture of the secondary lymphoid organs<\/a>\n\t\t\t\t\t<\/div>\n\t\t\t\t\t
Hosting organisation:<\/b><\/td>

Institute for Research in Biomedicine<\/p><\/td><\/tr>

Coordinator:<\/b><\/td>Marcus Thelen<\/td><\/tr>
IRB Participants:<\/b><\/td>

Marcus Thelen<\/a>, Group Leader<\/p><\/td><\/tr>

Partners:<\/b><\/td>

Cornelia Halin, ETH Z\u00fcrich, Institut f\u00fcr Pharmazeutische Wissenschaften (CH)<\/p>

Daniel Legler, Universit\u00e4t Konstanz, Biotechnologie Institut Thurgau (CH)<\/p>

Antal Rot, University of York (UK)<\/p><\/td><\/tr>

Research area:<\/b><\/td>

SNSF – Sinergia<\/p><\/td><\/tr>

Duration:<\/b><\/td>01.11.2015<\/span>\u00a0to\u00a031.10.2018<\/span><\/span><\/td><\/tr>
Website:<\/b><\/td>http:\/\/www.ackr.usi.ch<\/a><\/td><\/tr><\/tbody><\/table><\/section>

Atypical chemokine receptors (ACKR), unlike the classic (typical) chemokine receptors, do not trigger cell migration. These receptors rather act as decoy, eliminating or trancytosing chemokines. Research from the recent years has shown that ACKRs play a key role in the regulation of the chemokine system. In this project, the similarities and discrepancies of the function of three atypical receptors (ACKR1, ACKR3 and ACKR4) will be assessed.<\/p>

The group of atypical chemokine receptors (ACKR1-4) has recently been defined as receptors that are structurally related, although they do not follow the classical scheme of G-protein coupled receptors and do not interact with G-proteins. Nevertheless ACKRs can contribute through their capacity as effective eliminators of chemokines to form gradients. Francis Crick concluded already in the 70s that the persistence of spatial chemoattractant gradients requires the presence of corresponding sinks in juxtaposition to their sources. Such gradients of chemokines are essential for effective innate and adaptive immune responses.<\/p>

The project aims to demonstrate that gradients of chemokines exist in lymphoid tissue and, with a special focus on the function of ACKR. The consortium expects that the results will bring new insights into the regulation of immune response, which can be important, both in the fight against pathogens and in autoimmunity.<\/p><\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t\t\t

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\n\t\t\t\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<\/i><\/span>\n\t\t\t\t\t\t\t\t<\/i><\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t2012-2018: ABIRISK - Anti-Biopharmaceutical Immunization: Prediction and Analysis of Clinical Relevance to Minimize the Risk<\/a>\n\t\t\t\t\t<\/div>\n\t\t\t\t\t
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Hosting organisation:<\/b><\/td>\n\n

GlaxoSmithKline<\/p>\n<\/td>\n<\/tr>\n

Coordinator:<\/b><\/td>\nDaniel Sikkema, GlaxoSmithKline<\/td>\n<\/tr>\n
IRB Participants:<\/b><\/td>\n\n

Antonio Lanzavecchia<\/a>, Director<\/p>\n<\/td>\n<\/tr>\n

Research area:<\/b><\/td>\n\n

Innovative Medicines Initiative<\/p>\n<\/td>\n<\/tr>\n

Duration:<\/b><\/td>\n01.03.2012<\/span> to 28.02.2018<\/span><\/span><\/td>\n<\/tr>\n
Website:<\/b><\/td>\nhttp:\/\/www.abirisk.eu<\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<\/section>\n

Biopharmaceuticals are drugs that are biological in origin (i.e. are made of proteins or DNA for example) and are manufactured using biotechnology. A number of biopharmaceuticals are already in use and have dramatically improved quality of life for patients with serious, hard to treat conditions such as multiple sclerosis, Crohn\u2019s disease, diabetes, rheumatoid arthritis, haemophilia A and some cancers. However, in some patients, biopharmaceuticals can trigger an immune reaction, a phenomenon known as immunogenicity. When this happens, the immune system produces antibodies (ADAs) that neutralise the drug, which can reduce the effectiveness of the biopharmaceutical. In some patients, the immune response causes side effects such as a rash, chest pains, or a fall in blood pressure. In the most severe cases, it can trigger anaphylactic shock and even prove fatal.<\/p>\n

Immunogenicity \u2013 the known unknowns<\/strong><\/p>\n

Diverse factors appear to be involved in immunogenicity. On the drug side, both the compound and the route and duration of administration seem to play a role, while on the patient side, the type of disease, age, genetic background and interactions with other medicines may be risk factors.<\/p>\n

Therefore it is extremely hard to predict which biopharmaceuticals will have immunogenicity problems; although many tests exist, these are not always accurate. Furthermore, knowing which patients are at greatest risk of mounting an immune response to a given biopharmaceutical is extremely difficult.<\/p>\n

Reducing the risks<\/strong><\/p>\n

Yet even though immunogenicity continues to pose a problem in the development of new drugs, until now there has been no major effort to solve the problem.<\/p>\n

Enter the ABIRISK project, which aims to give biopharmaceuticals a much-needed boost and represents the first concerted effort to tackle the immunogenicity problem by bringing together leading experts from hospitals, academia, industry, and small companies.<\/p>\n

The kick-off meeting for the ABIRISK project took place in Paris on March 1st<\/sup>-2nd<\/sup>, 2012. The ABIRISK project consortium is presently made up of thirty-five partners, twenty-four of which are academic institutions, nine are EFPIA member companies and two are small and medium enterprises (SMEs). Thirteen countries are represented: The United Kingdom, France, Italy, Germany, Switzerland, Denmark, Belgium, the Netherlands, Spain, Sweden, Austria, Israel and Czech Republic.<\/p>\n

The project will set up laboratory tests to probe the immunogenicity of several biopharmaceuticals that are already used on patients. The scientists will then match their test findings with the effect the drug actually has on patients. This will help the team to develop tools that are better at predicting immunogenicity during drug development.<\/p>\n

Many pharmaceutical companies, academic institutions and patient registries have large amounts of data on biopharmaceuticals and patients\u2019 responses to them. In ABIRISK, these diverse databases will be assembled into a single immunogenicity databank that will help researchers pinpoint the factors that influence a drug\u2019s immunogenicity and patients\u2019 risk of it. This will allow the researchers to generate tools that will accurately predict whether a patient will mount an immune response to a biopharmaceutical and how that immune response will affect the efficacy and safety of the drug.<\/p>\n

Safer, more effective drugs for patients<\/strong><\/p>\n

Immunogenicity means many patients today are denied the life-changing benefits of biopharmaceuticals. ABIRISK will ultimately result in a new generation of biopharmaceuticals with lower immunogenicity that can be safely and effectively used by more patients. In addition, the project will allow clinicians to determine which patients will respond best to which biopharmaceutical, thereby preventing patients from suffering the side effects of a drug that does not suit them.<\/p>\n

For Europe\u2019s pharmaceutical industry, better tests will help companies identify the safest, most effective biopharmaceuticals and weed out those that pose a high immunogenicity risk earlier in the drug development process. This will save companies both time and money. Finally, by adding to our knowledge of the mechanisms behind immunogenicity, the project will help to improve regulatory guidelines for the approval of biopharmaceuticals.<\/p><\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t\t\t

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\n\t\t\t\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<\/i><\/span>\n\t\t\t\t\t\t\t\t<\/i><\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t2014-2017: Sinergia 154421 - ER-phagy mechanisms to maintain and restore endoplasmic reticulum homeostasis<\/a>\n\t\t\t\t\t<\/div>\n\t\t\t\t\t
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Hosting organisation:<\/b><\/td>\n\n

Institute for Research in Biomedicine<\/p>\n<\/td>\n<\/tr>\n

Coordinator:<\/b><\/td>\nMaurizio Molinari<\/td>\n<\/tr>\n
IRB Participants:<\/b><\/td>\n\n

Maurizio Molinari<\/a>, Group Leader<\/p>\n<\/td>\n<\/tr>\n

Partners:<\/b><\/td>\n\n

Matthias Peter, Department of Biology, Institute of Biochemistry, ETH Z\u00fcrich (CH)<\/p>\n

Fulvio Reggiori, Department of Cell Biology, University of Groningen, Groningen (NL)<\/p>\n<\/td>\n<\/tr>\n

Research area:<\/b><\/td>\n\n

SNSF – sinergia<\/p>\n<\/td>\n<\/tr>\n

Duration:<\/b><\/td>\n01.10.2014<\/span> to 30.09.2017<\/span><\/span><\/td>\n<\/tr>\n
Website:<\/b><\/td>\nhttp:\/\/p3.snf.ch\/project-154421<\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<\/section>\n

The endoplasmic reticulum (ER) is the site of folding and assembly for about a third of the eukaryote proteome. This membrane-bound organelle contains high concentrations of molecular chaperones and enzymes that 1) prevent aggregation of non-native newly synthesized polypeptides, 2) catalyze rate-limiting reactions of the protein folding process, and 3) insure that only native and fully-assembled proteins can leave the compartment to be transported to their intra- or extracellular functional site. The ER also contains molecular chaperones and enzymes that recognize terminally misfolded polypeptides and orphan subunits of oligomeric complexes, extract them from the folding environment and regulate their transport across the ER membrane for delivery into the cytosol where they are degraded by proteasomes. This process is known as ER-associated degradation (ERAD). Balanced activity of the ER folding and ERAD machineries is instrumental to maintain cellular homeostasis. A substantial increase in the ER cargo load, accumulation of misfolded polypeptides and environmental changes elicit an adaptation program known as the unfolded protein response (UPR). The UPR is triggered by ER stress sensors embedded in the ER membrane, and involves the activation of transcriptional\/translational programs resulting in expansion of the ER volume, attenuated synthesis of ER cargo proteins and increased production of ER-resident chaperones and enzymes. Emerging evidence shows that the specific engulfment of part of the ER into autophagosomes through a selective type of autophagy, which has been named ER-phagy or reticulophagy, plays a key role in the maintenance of ER homeostasis in two important aspects of the cell response to ER stress. First, ER-phagy teams up with the ERAD machinery to clear accumulated protein aggregates from the ER. Second, it counteracts the uncontrolled expansion of the ER that occurs during ER stress. If UPR activation does not alleviate the ER stress or does not allow adaptation to it, cell death programs are activated. In contrast, if the cellular response relieves the stress condition, a recovery phase starts whereby the volume of the ER and the content of ER-resident proteins return to pre-stress levels. Our preliminary data lead us to propose a third role for ER-phagy in reducing the ER size and content during the recovery phase initiated upon termination of ER stress.<\/p>\n

The major goal of this collaborative project is to identify the components and regulatory mechanisms underlying ER-phagy during cell recovery from ER stresses, which, to our knowledge, has remained totally unexplored until now. We will closely collaborate among 3 leading research groups, two in Switzerland and one in the Netherlands, to exploit our complementary experimental expertise and model systems (budding yeast and mammalian cells). Identified factors and principles will also be tested in the context of the two documented types of ER-phagy, i.e. clearance of ER aggregates and buffering ER expansion, to also shed light onto these poorly characterized processes and to determine whether ER-phagy operates through similar mechanisms under different stimulus conditions. Our studies will reveal important aspects of the coordinated cross talk between ER quality control, ER stress, ERAD and ER-phagy, which is crucial to maintain cell and organism homeostasis. The importance of these studies is highlighted by the growing interest and clinical use of proteostasis-modifying substances and autophagy modulators to contrast the onset and progression of several diseases caused by protein misfolding that leads to the accumulation of toxic aggregates.<\/p><\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t\t\t

\n\t\t\t\t\t
\n\t\t\t\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<\/i><\/span>\n\t\t\t\t\t\t\t\t<\/i><\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t2013-2016: Sinergia 147662 - Tuning of immune homeostasis and immune response by persistent viral infections<\/a>\n\t\t\t\t\t<\/div>\n\t\t\t\t\t
\n\n\n\n\n\n\n\n\n\n
Hosting organisation:<\/b><\/td>\n\n

Institute for Research in Biomedicine<\/p>\n<\/td>\n<\/tr>\n

Coordinator:<\/b><\/td>\nAntonio Lanzavecchia<\/td>\n<\/tr>\n
IRB Participants:<\/b><\/td>\n\n

Antonio Lanzavecchia<\/a>, Director<\/p>\n<\/td>\n<\/tr>\n

Partners:<\/b><\/td>\n\n

Thierry Calandra, Infectious Disease Service, Department of Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne (CH)<\/p>\n

Annette Oxenius, Institute for Microbiology, ETH Z\u00fcrich, Z\u00fcrich (CH)<\/p>\n

Giuseppe Pantaleo, Division of Immunology and Allergology, Centre Hospitalier Universitaire Vaudois, Lausanne (CH)<\/p>\n<\/td>\n<\/tr>\n

Research area:<\/b><\/td>\n\n

SNSF – Sinergia<\/p>\n<\/td>\n<\/tr>\n

Duration:<\/b><\/td>\n01.08.2013<\/span> to 31.07.2016<\/span><\/span><\/td>\n<\/tr>\n
Website:<\/b><\/td>\nhttp:\/\/p3.snf.ch\/project-147662<\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<\/section>\n

The immune response relies on the coordinated action of different cells of the immune system, which are constantly confronted with commensal microorganisms (microbiome) and with persistent viral infections (virome). In contrast to the microbiome, which has been shown to modulate the immune response, the virome received much less attention. This project therefore aims at assessing how the virome impacts the composition, properties and function of immune cells, in both humans and animal models.<\/p>\n

In this project, we aim to understand to what extent chronic viral infections impact on the response to vaccines, on the susceptibility to infection, on the predisposition to autoimmunity and on the acceleration of immunological ageing. Three research and clinical centers located in Bellinzona, Lausanne, and Zurich will cooperate to reach this ambitious goal. They will take advantage of complementary expertise and resources to study well defined cohorts of patients with chronic viral infections using state-of-the-art analytical technologies such as multiparameter and mass-tag barcoding flow cytometry, single cell gene expression profiling, high throughput cellular screening methods and with next generation repertoire sequencing. Studies in mouse models of chronic infection will complement and synergize with the human studies. By combining the data obtained in the three centers this Sinergia project will give rise to the most comprehensive view of the impact of chronic viral infections on the homeostasis and the functionality of the immune system.<\/p><\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t\t\t

\n\t\t\t\t\t
\n\t\t\t\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<\/i><\/span>\n\t\t\t\t\t\t\t\t<\/i><\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t2011-2016: ADITEC - Advanced Immunization Technologies<\/a>\n\t\t\t\t\t<\/div>\n\t\t\t\t\t
Hosting organisation:<\/b><\/td>

Sclavo Vaccines Association (SVA)
Piazza La Lizza, Siena, Italy<\/p><\/td><\/tr>

Coordinator:<\/b><\/td>Rino Rappuoli<\/td><\/tr>
IRB Participants:<\/b><\/td>

Antonio Lanzavecchia<\/a>, Director<\/p>

Federica Sallusto<\/a>, Group Leader<\/p>

Mariagrazia Uguccioni<\/a>, Group Leader, Vice Director<\/p><\/td><\/tr>

Research area:<\/b><\/td>

HEALTH.2011.1.4-4 High impact initiative for better immunisation<\/p><\/td><\/tr>

Duration:<\/b><\/td>01.10.2011<\/span>\u00a0to\u00a030.09.2016<\/span><\/span><\/td><\/tr>
Website:<\/td>http:\/\/www.aditecproject.eu<\/a>
http:\/\/www.aditecproject.eu\/fileadmin\/user_upload\/Documenten\/News\/Publication_Im…<\/a><\/td><\/tr><\/tbody><\/table><\/section>

Vaccines so far have been developed mostly by following an empiric approach. To prevent and possibly cure unresolved and emerging infectious diseases we need to fully exploit the potential of the human immune system. Progress in science and technology makes it possible to achieve what was previously deemed impossible. The scope of this project is to produce knowledge necessary to develop novel and powerful immunization technologies for the next generation of human vaccines. This goal requires a multidisciplinary approach in which diverse but complementary scientific disciplines and technologies converge. Therefore some of the most competitive European research groups from public institutions and biotechs have agreed to join forces in ADITEC, together with top US groups on systems biology and adjuvants to support this enterprise.<\/p>

A systems biology approach will be used to study licensed and experimental vaccines in patient characterization studies and in clinical trials, to investigate the effect of adjuvants, vectors, formulations, delivery devices, routes of immunization, homologous and heterologous primeboost schedules, as well as the impact of host factors such as age, gender, genetics and pathologies. Animal models will be used to complement human studies, and to select novel immunization technologies to be advanced to the clinic.<\/p>

To address these issues in a coordinated manner, ADITEC is organised on a matrix structure in which research themes and experimental approaches feed into each other. Training curricula will be created to impact on the formation of the next generation of EU researchers in the field. ADITEC scientists and institutions are part of the Sclavo Vaccines Association (SVA), which is dedicated to vaccines and vaccine research. SVA, acting as the coordinating institution, guarantees the long-term commitment and sustainability of this initiative, beyond the duration of ADITEC itself.<\/p><\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t\t\t

\n\t\t\t\t\t
\n\t\t\t\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<\/i><\/span>\n\t\t\t\t\t\t\t\t<\/i><\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t2011-2016: IDAMS - International Research Consortium on Dengue Risk Assessment, Management, and Surveillance<\/a>\n\t\t\t\t\t<\/div>\n\t\t\t\t\t
Hosting organisation:<\/b><\/td>

Universit\u00e4tsklinikum Heidelberg
im Neuenheimer Feld 672, Heidelberg, Germany<\/p><\/td><\/tr>

Coordinator:<\/b><\/td>Thomas Jaenisch<\/td><\/tr>
IRB Participants:<\/b><\/td>

Federica Sallusto<\/a>, Group Leader<\/p><\/td><\/tr>

Research area:<\/b><\/td>

HEALTH.2011.2.3.3-2 Comprehensive control of Dengue fever under changing climatic conditions<\/p><\/td><\/tr>

Duration:<\/b><\/td>01.09.2011<\/span>\u00a0to\u00a031.08.2016<\/span><\/span><\/td><\/tr>
Website:<\/b><\/td>http:\/\/www.idams.eu\/<\/a><\/td><\/tr><\/tbody><\/table><\/section>

The overall concept of this research project is to assemble a consortium of international experts working together to develop new and innovative tools to be applied to the control of dengue in a global context. The core of the application focuses on parallel strategies aimed at:<\/p>