Bilaga 3. Expertpanelernas slutgiltiga yttranden per område

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1 Bilaga 3 Expertpanelernas slutgiltiga yttranden per område

2 Slutgiltiga yttranden Expertpanelen inom Cancer

3 Dnr Efternamn, Förnamn Eriksson, Per Filip Billy Lunds universitet Bidragsform Strategiska forskningsområden Projekttitel BioCARE - biomarkörer i cancermedicin Ämnesområde/målområde Medicin Beredningsgrupp Cancer (VR-St-Can) Evaluation form Strategic research areas panel evaluation 1. Evaluate scientific quality by international comparison (scale:1-5) based on: A) - scientific quality. B) - potential development of the scientific environment. C) - how the area is prioritised among the applicant s activities to generate the conditions for scientific excellence. D) - strategies to increase Sweden s international scientific competitiveness in the research area. Assessment note: The "biocare" proposal is sponsored by the universities of Lund and Goteborg. The leading scientists involved in the proposal have strong publication records, with numerous publications in highly ranked journals. Ake Borg and Joachim Dillner appear to have a particularly strong track record. The main scientific achievements of the participants are well summarized in the proposal. We conclude that the participants form a very active group of highly competent medical scientists with a strong research focus. This provides a strong basis for the pursuit of their biomarker program. One may regret that the proposal lacks a strikingly innovative element. The scientific environment is already strong and it has high potential for development because of the availability of a large population of cancer patients, particularly breast cancer patients, and well established technological platforms. The proposal involves the creation of a jointly run research school to organize a doctoral program. It also involves the creation of half-time positions enabling clinicians to carry out significant research programs.this is very commendable. 2. Evaluate strategic importance to the business sector and society (scale: 1-5) based on: A) - why, and in what way, the research area is, or can become, strategically important for the business sector and society. B) - strategies and plans to generate benefits from research findings in the research area. C) - capacity and supportive activities to generate benefits from research findings in the research area. D) - engagement and participation of the business sector, industrial research institutes, and other community organisations in problem formulation and implementation. Assessment note: The societal impact includes potential new diagnostics and treatments for cancer, development of new approaches for cancer prevention, increased potential of success for current drug therapies through personalized treatment regimens. There will be increased economic development through job creation and generation of new start-up companies The strategies to translate research findings into new therapies are sound. 3. Evaluate the need for infrastructure - The need for infrastructure is not a criterion for assessing the application s quality, but the comments highlight the infrastructure that currently exists and that which needs to be financed to enable implementation of the proposed research programme. Comments: No major purchase of new equipment is requested as advanced platforms are already available. However, these platforms will require constant upgrading at a significant cost. 4. Overall grade (scale:1-5) 4 (1=Insufficient, 2=Good, 3=Very good, 4=Excellent, 5=Outstanding) The panel s summary of the application s quality in relation to the criteria listed above. This is an excellent application from a very good research institution aiming at coordinating their current cancer research efforts. The strengths lie in the strong group of highly productive scientists who will populate this Center, the strategic approach to the expansion of current cancer research capabilities, the existence of excellent core facilities/databases, new efforts to train and support young cancer researchers, strong alliances with hospitals and companies that will allow translation of basic findings into the clinical arena.there is confidence among the panel members that funding of this initiative will lead to new discoveries that can be translated into better cancer diagnosis/prevention/treatment. Beredningsgruppens yttrande VR-St-Can, Eriksson, Per Filip Billy

4 Dnr Efternamn, Förnamn Wallberg-Henriksson, Harriet Karolinska Institutet Rektor Bidragsform Strategiska forskningsområden Projekttitel Centrum för Integrerad Cancerforskning vid Karolinska Institutet (CICS-KI) -en miljö för translatorisk cancerforskning Ämnesområde/målområde Medicin Beredningsgrupp Cancer (VR-St-Can) Evaluation form Strategic research areas panel evaluation 1. Evaluate scientific quality by international comparison (scale:1-5) based on: A) - scientific quality. B) - potential development of the scientific environment. C) - how the area is prioritised among the applicant s activities to generate the conditions for scientific excellence. D) - strategies to increase Sweden s international scientific competitiveness in the research area. Assessment note: A) Scientific Quality This is a highly ambitious and sophisticated proposal from a world class institution to develop a Center for Integrated Cancer Studies (CICS). The major strength of the proposal lies in the high quality multidisciplinary scientific consortium that will oversee and populate this initiative, the pre-existing research infrastructure (core facilities, registries, laboratories) that will form the basis for the CICS, the relevance of the four focus areas to the future of cancer diagnosis, treatment and prevention, and the already-established relationships with internal and external partners to move findings towards commercialization. The majority of the research focus relies heavily on the documented expertise of the current faculty, a strategic decision that enhances the likelihood of success. The recent addition of Drs. Ohlsson and Taipale both broadens and strengthens an already strong cadre of scientists and brings new technology to the enterprise. The two infrastructure initiatives a molecular pathology facility dedicated to tissue microarrays and IHC, as well as a pre-clinical trial facility for the in-depth analysis of mouse and cell culture tumor models again build on existing and complementary strengths within the institute, although some of the details as to how these facilities will be operated remain vague. B) A number of educational initiatives have been proposed, including focused support for postdoctoral trainees and MD-PhD and residency programs. These initiatives seem appropriate, although the proposal would have benefitted from a more detailed description of curriculum development and other programmatic features to determine whether this initiative is particularly innovative, and whether it will indeed surpass current approaches to training future clinician scientists. A strategic investment in the recruitment of junior scientists is also viewed positively, although a discussion of the mentoring activities that will be in place to assure their success was lacking. C) Overall, there has been an impressive and strategic investment in KI s research infrastructure over recent years (250MSEK), including the development of cancer-focused research centers of excellence, state-of-the-art core facilites and SCS research grants (of which KI holds 41%). All this bodes well for the success of this new venture. KI has also been recognized as an international leader in cancer research, as evidenced by publications in top-rate international journals, leadership participation in international symposia/panels, and procurement of research grants from international agencies (including NIH and AICR). D) The Karolinska Institute enjoys an excellent international reputation, and a number of the cancer researchers collaborating in the current effort are leaders in their field. The proposed coordination and expansion of research infrastructure and training should enhance Sweden s international scientific competitiveness. The development of an international SAB to evaluate ongoing and planned research will be a critical factor in this regard. 2. Evaluate strategic importance to the business sector and society (scale: 1-5) based on: A) - why, and in what way, the research area is, or can become, strategically important for the business sector and society. B) - strategies and plans to generate benefits from research findings in the research area. C) - capacity and supportive activities to generate benefits from research findings in the research area. D) - engagement and participation of the business sector, industrial research institutes, and other community organisations in problem formulation and implementation. Assessment note: Beredningsgruppens yttrande VR-St-Can, Wallberg-Henriksson, Harriet

5 A) The impact on society and the business sector include: potential new diagnostics/treatments for cancer, development of new approaches for cancer prevention, increased potential of success for current drug therapies through personalized treatment regimens, decreased sick time = increased job performance, increased economic development through job creation (within KI), generation of new start-up companies, influx of support from large pharmaceutical/ medical device companies, training of highly competent and sought-after young clinical translational scientists, international recognition for new cancer initiatives. B) The strategies to translate research findings into new therapies are sound, and focus on moving new discoveries into the clinical setting (enhanced by the existence of a comprehensive Clinial Trials unit) and commercialization of new diagnostics/therapies. C) The collaboration between KI and the Stockholm County Council provides KI with a partnership with which to develop/support research infrastructure, more effectively move new discoveries into the clinical setting, and broadly impact clinical education. With regard to commercialization of novel discoveries, the Karolinska Institute has an advantage as an academic center in that it has already established an internal commercialization infrastructure in the Karolinska Institutet Innovation system that guides its faculty researchers from initial commercialization through potential business partnerships. This can decrease the risks that may be associated with potential new technologies/therapies, both from a financial and operational standpoint, thereby encouraging industry partnership and product commercialization. D) Pre-existing strategic relationships with the SCC, the new Karolinska University Hospital, Karolinska Institutet Park (an incubator), Karolinska Institutet Development AB (an independent investment company), University start-ups in strategic areas, as well as major pharmaceutical companies such as Astra-Zeneca will help to position new research findings on the fast track to commercialization. The identification of new targets for cancer diagnosis/prevention/treatment and their validation will help to feed the industry drug development pipeline. 3. Evaluate the need for infrastructure - The need for infrastructure is not a criterion for assessing the application s quality, but the comments highlight the infrastructure that currently exists and that which needs to be financed to enable implementation of the proposed research programme. Comments: The applicants propose two infrastructure initiatives. The first is a molecular pathology laboratory with three aims: 1) TMA using mouse and human tumor samples to evaluate the relevance of potential cancer-related proteins, 2) tissue banking for human tumors to be used for analysis and the development of primary cultures, and 3) expansion of the existing mouse tissue analysis (MTA) unit with the addition of veterinary pathologists. This new infrastructure will work in collaboration with a number of pre-existing units, including the Swedish registry system, the Human Protein Atlas of unique antibodies, the SciLife Laboratory Initiative (Bioimaging), the mouse phenotypic analysis unit and the MTA. There is clear justification for this infrastructure need. The second infrastructure described is a Preclinical Trial facility, with a primary purpose of housing a variety of mouse tumor models, and providing the necessary technology for their analysis (imaging, FACs). A second effort will be directed at developing new mouse models. Enthusiasm for this would be enhanced if more detail had been provided as to how this will be accomplished, how mouse tumor models will be chosen, how the facility will be operated (fee for service?) and what the role will be for of each of the proposed personnel will be (an equal number of technicians and students/postdocs are proposed it is not clear what role the trainees will play, nor how their training will be accomplished). That said, a facility with this capability would be highly beneficial to the cancer researchers at KI. 4. Overall grade (scale:1-5) 4 (1=Insufficient, 2=Good, 3=Very good, 4=Excellent, 5=Outstanding) The panel s summary of the application s quality in relation to the criteria listed above. This is an excellent application from an outstanding research institution to coordinate their current cancer research efforts under a new Center for Integrated Cancer Studies. The strengths lie in the strong group of highly productive scientists who will populate this Center, the strategic approach to the expansion of current cancer research capabilities, the existence of excellent core facilities/databases and plans to develop additional ones, new efforts to train and support young cancer researchers, strong alliances with both healthcare and government entities that will allow translation of basic findings into the clinical arena, a management team that will bring together academic and government leaders to determine overall strategy and resource allocation, and a strong plan/infrastructure for commercialization of discoveries. The few minor criticisms do not detract from the enthusiam for this proposal, and there is confidence among the panel members that funding of this initiative will lead to new discoveries that can be translated into better cancer diagnosis/prevention/treatment. Beredningsgruppens yttrande VR-St-Can, Wallberg-Henriksson, Harriet

6 Dnr Efternamn, Förnamn Hallberg, Anders Uppsala universitet Universitetsledningens kansli Bidragsform Strategiska forskningsområden Projekttitel The U-Can Comprehensive Cancer Consortium Ämnesområde/målområde Medicin Beredningsgrupp Cancer (VR-St-Can) Evaluation form Strategic research areas panel evaluation 1. Evaluate scientific quality by international comparison (scale:1-5) based on: A) - scientific quality. B) - potential development of the scientific environment. C) - how the area is prioritised among the applicant s activities to generate the conditions for scientific excellence. D) - strategies to increase Sweden s international scientific competitiveness in the research area. Assessment note: The U-Can Comprehensive Cancer Consortium (UCAN) is a proposal, put forward jointly by the University of Uppsala (UU) and the University of Umea (UMU), that aims to strengthen their research activities and research output in the cancer area. The two main applicants will also collaborate with the Royal School of Technology (KTH), who have a high level of know-how in engineering, and with Stockholm University (SU), on account of their expertise in nucleic acids and bio-informatics. The proposal is based on and draws its strength from a broad range of already existing research activities in the cancer area in UU and UMU. Specifically, UU and UMU together look after about 30% of all cancer patients in Sweden, they have experience with clinical trials, and they expect that within a few years some 80% of cancer patients will be treated within clinical trials. But the main asset of the proposal lies in the excellent to outstanding scientific track record of the investigators, both on the basic science and on the clinical side: for instance, Lena Claesson-Welsh in angiogenesis, Anders Bergh in prostate cancer, Bengt Glimelius in clinical oncology, Carl-Henrik Heldin for his pioneering work on the PDGF and TGF-b signaling pathways, Thomas Helleday in the area of DNA repair, Ulf Landegren in innovative methodologies for DNA and protein analysis, Fredrik Ponten in proteomics, Britt Skogseid in endocrine tumors. Finally, it should be mentioned that Tobias Sjöblom was the first author in a ground breaking paper ( The consensus coding sequences of human breast and colorectal cancers, published in 2006, when he was working at Johns Hopkins in the laboratory of Vogelstein and Kinzler). The proposal is ambitious, as it ranges from molecular and cell biology to finding new prognostic markers, to finding new drugs and testing them in phase I trials. On the clinical side, research is planned on a wide range of malignancies, including colorectal, endocrine, haematological, brain, prostate, and there is appropriate emphasis on advance imaging and radiotherapy. From the point of view of clinical cancer research, the existence and further development of a tumor tissue bank is to be regarded as especially valuable, and it will naturally provide material for further efforts in defining the spectrum of somatic mutations in all the tumors mentioned. Undoubtedly the basic work on signalling pathways, angiogenesis and DNA repair will continue to bear fruit, and it should be ideally integrated with the clinical work. Thus, there is little doubt in our minds that through UCAN Sweden scientific competitiveness in cancer research will be enhanced. For most of the scientists and for all the clinical scientists involved cancer seems to be already the priority area: this is likely to encourage young people who have these scientists as mentors to enter this aresa, and this will be conducive to further developing excellence in cancer research. Perhaps because of the format of the application, whereby specific research projects were not presented, at places the writing lacks focus. For instance, the boxes and arrows diagram in Fig 1 of Appendix 2 is rather vague, and in that section of the application there is no prioritization among finding new mutant genes, defining mutational landscapes in specific subsets of tumors, identifying drug-resistance mutations versus mutant clones selected by drugs, and targeting known mutant genes: it is unlikely that all of this can be done for all tumors within the time span of the current UCAN application. With respect to management, it is not quite clear from Fig 2 of Appendix 4 how it is going to work: it is good for the Director to have a Steering Committee to support her: but the Committee should steer, whereas the Director must be responsible for running UCAN. In this respect, she should be able to appoint a Deputy in Umea and, if she sees so fit, additional deputies for specific areas. The management structure proposed including a deputy director in Umea and the role of a steering committe as an executive committee, with the role of helping the director to implement the programme, would be satisfactory. In conclusion, the Panel feel that this application is of high calibre and that it fulfils the criteria of scientific quality itemized in the Call for Grant Applications: Strategic Research Areas. 2. Evaluate strategic importance to the business sector and society (scale: 1-5) based on: A) - why, and in what way, the research area is, or can become, strategically important for the business sector and society. B) - strategies and plans to generate benefits from research findings in the research area. C) - capacity and supportive activities to generate benefits from research findings in the research area. D) - engagement and participation of the business sector, industrial research institutes, and other community organisations in problem formulation and implementation. Assessment note: Beredningsgruppens yttrande VR-St-Can, Hallberg, Anders

7 It is evident that cancer research is strategically important for society and for the business sector. UCAN can contribute substantially in terms of potential new diagnostics and eventually improved treatment for various types of cancer, increased potential of success for current drug therapies through personalized treatment regimens, decreased sick time = increased job performance, increased economic development through job creation, generation of new start-up companies, influx of support from large pharmaceutical/ medical device companies, training of highly competent and sought-after young clinical translational scientists, international recognition for new cancer initiatives. The components of UCAN have an excellent record of collaboration with industry and there is every reason to expect this can continue. In this respect, pre-existing relationships will help. The training of young people with role-models of high caliber will be especially valuable. 3. Evaluate the need for infrastructure - The need for infrastructure is not a criterion for assessing the application s quality, but the comments highlight the infrastructure that currently exists and that which needs to be financed to enable implementation of the proposed research programme. Comments: There is good infrastructure already in place, the additional items proposed will strengthen the infrastructure appropriately. 4. Overall grade (scale:1-5) 4 (1=Insufficient, 2=Good, 3=Very good, 4=Excellent, 5=Outstanding) The panel s summary of the application s quality in relation to the criteria listed above. In summary, this is an excellent proposal that benefits from the efforts of scientists who are eminent in cancer research and who clearly intend to work collegially. We confidently anticipate that the research output will continue to be of a high quality, that it will improve cancer care, and it will have a positive impact on the training of oncologists and of young people who intend to devote themselves to cancer research. Beredningsgruppens yttrande VR-St-Can, Hallberg, Anders

8 Slutgiltiga yttranden Expertpanelen inom Diabetes

9 Dnr Efternamn, Förnamn Eriksson, Per Filip Billy Lunds universitet Bidragsform Strategiska forskningsområden Projekttitel EXODIAB (Framstående Diabetesforskning i Sverige) Ämnesområde/målområde Medicin Beredningsgrupp Diabetes (VR-St-Dia) Evaluation form Strategic research areas panel evaluation 1. Evaluate scientific quality by international comparison (scale:1-5) based on: A) - scientific quality. B) - potential development of the scientific environment. C) - how the area is prioritised among the applicant s activities to generate the conditions for scientific excellence. D) - strategies to increase Sweden s international scientific competitiveness in the research area. Assessment note: EXODIAB is a joint strategic diabetes research initiative between Lund University (70% of overall funds) and Uppsala University (30% of overall funds) to develop new strategies for early risk assessment and novel therapies for prevention and treatment of diabetes and its complications. The consortium comprises an outstanding group of 10 investigators focused on several aspects of both type 1 and type 2 diabetes (T1D and T2D, respectively) to be led by Drs. Åke Lernmark and Leif Groop, outstanding researchers in diabetes and highly qualified to lead the effort. Lund University and Uppsala University have selected diabetes for their overall strategic planning for research emphasis areas. Seven projects are proposed aimed to: 1) identify the underlying molecular events leading to T1D and T2D and test the pathways involved for their potential as novel drug targets, 2) design a panel of biomarkers and genetic markers, which may predict T1D and T2D and development of diabetic complications, 3) test whether vaccination can be used to prevent T1D, 4) exploit novel dietary concepts and functional food for prevention and management of diabetes and obesity, 5) create a national Human Tissue and Islet Research Resource for the cure of diabetes, 6) create a novel endocrine organ at an extrahepatic site for clinical islet transplantation, and 7) test means to prevent micro-and macrovascular complications in diabetes. The focus on both Type 1 and Type 2 diabetes provides an opportunity to better define the parameters of each disease, as well as to investigate the disease continuum. For example, the exploration of whether non-autoimmune processes contribute to beta-cell damage in T1D is an opportunity to determine whether therapies such as exenatide and GLP-1 analogs may have a place in T1D treatment. Lund University (LU) is actively collaborating with selected universities worldwide in research and in the exchange of faculty. In the diabetes area LU co-operates with the Broad Institute at MIT/Harvard, Oxford University, Helsinki University as well as with a large number of universities as part of other research consortia. There are agreements with about 660 universities (about 450 in Europe) in undergraduate and graduate education. It is stated that LU has the largest international exchange of all the Swedish universities among its teachers and researchers. For diabetes, examples of ongoing EU-projects include ENGAGE, EXGENESIS, EURODIA, CEED3, DIAPREPP and the Innovative Medicine Project SUMMIT (Surrogate markers for vascular endpoints in diabetes). Particularly important to this consortium is to seek the recruitment of junior faculty research positions in strategic areas of diabetes. Postdoctoral fellowships are also included, especially for study abroad before returning to Sweden for more advanced positions. In this respect, plans are underway to include executive management courses in attempts to develop better strategies towards gender equity. The application would have benefitted from a more formal presentation of program priorities, especially in areas that affect both T1D and T2D research programs as well as from details referent to the coordination of the different research projects. Concerning the islet programs, the panel recommends that the islet expertise remains in Uppsala and that duplicating the effort in Lund will not be well justified. 2. Evaluate strategic importance to the business sector and society (scale: 1-5) based on: A) - why, and in what way, the research area is, or can become, strategically important for the business sector and society. B) - strategies and plans to generate benefits from research findings in the research area. C) - capacity and supportive activities to generate benefits from research findings in the research area. D) - engagement and participation of the business sector, industrial research institutes, and other community organisations in problem formulation and implementation. Assessment note: The strategic importance of this application is apparent in the already developed consortia such as SUMMIT which includes 18 European universities, a database company and 5 pharma industries including AstraZeneca, Roche, Lilly, and Boehringer Ingelheim to facilitate and shorten development of drugs for prevention and treatment of diabetic complications. This initiative will create one of the world s largest data bases on novel genetic markers and biomarkers for diabetic complications (over 10,000 people with these complications will undergo WGAS, and biomarker discovery, including metabolomics). The database is operated by LUDC. In addition, EXODIAB has the largest and best characterized biobanks for diabetes research in the world totaling over 100,000 individuals, with DNA extracted and serum stored for biomarker analyses. This is an invaluable tool to the business sector and to society in general.

10 The group has a strong track-record in industrial collaborations. Examples include: 1. Diagnostics & Biomarkers, 2. Therapeutic targets, 3. Regenerative medicine, 4. Know-how, i.e. Health economics and Social Medicine, and 5. Clinical Trial Unit. Proofs of engagement and participation with the business sector include the commercialization of vaccines against atherosclerosis. In addition, three different strategies are being developed commercially: Apo AI Milano for treatment of coronary disease (Pharmacia, Upjohn, Pfeizer), recombinant apob antibodies for prevention of coronary disease (Bioinvent, Genentech) and an apob peptide-based atherosclerosis vaccine. The EXODIAB research group has a strong basic and translational infrastructure that facilitates the application of basic discovery to patent evaluation/application and business development through the DIABRIGE product/business management arm of the program. The targeted research areas of gene/protein discovery, islet biology, clinical trials and population health are all considered to be timely and appropriate priorities of this program. There is a clear track record for developing and/or participating in regional and global research consortia that promises to keep this program at the forefront of diabetes research. The translational aspect of the program for future business development is quite strong. Thus, this consortium is positioned to have significant impact in diabetes, while promoting business/economic development in diagnostics and therapeutics. 3. Evaluate the need for infrastructure - The need for infrastructure is not a criterion for assessing the application s quality, but the comments highlight the infrastructure that currently exists and that which needs to be financed to enable implementation of the proposed research programme. Comments: In general EXODIAB partners have access to an excellent equipment infrastructure to support the research. However, some areas need to be updated in order to stay competitive. For example, deep sequencing, not only of exons and cdna but also of whole genomes is now a reality and it will require a significant investment in the best available DNA sequencers. Other potential areas include mass spectrometry for metabolomic studies, cell sorting using FACS, MRI and PET for animal studies and nanotechnology for biomarker discovery. Presently there is an excellent current basic and clinical research infrastructure to strongly support this diabetes initiative. The requested budget support for research positions, education, and equipment will appropriately augment the physical and academic quality of this outstanding research group. 4. Overall grade (scale:1-5) 4 (1=Insufficient, 2=Good, 3=Very good, 4=Excellent, 5=Outstanding) The panel s summary of the application s quality in relation to the criteria listed above. This consortium of investigators from Lund University and Uppsala University comprises an outstanding group of experienced, internationally recognized leaders in diabetes research. There are a variety of strengths in this broad spectrum of diabetes-related research including genetics, autoimmunity, islet biology/transplantation, nutrition/metabolism, and disease-related complications. The fact that this group has a blend of investigators focused on both Type 1 and Type 2 diabetes research is especially attractive and makes this group adaptable to the rapid conceptual changes occurring in the field. The reviewers were overall impressed by the application and rated it highly. Strategies to increase Sweden s competitiveness at the academic level as well as at the business sector and society levels have been implemented as demonstrated by the several collaborations already existing with other universities in Sweden, Europe and the United States. Business areas in need of exploration have been identified, prioritized and partnerships also already developed or under consideration for early future developments. A valuable aspect of the application is the inclusion of a human tissue Laboratory to provide access to tissue from human islets as well as target tissues for insulin action. The translational aspect of the program for future business development is quite strong. Thus, this group is positioned to both impact the major societal health care burden imposed by diabetes and to promote business/economic developments in diagnostics and therapeutics. The plan to create academic positions for research sabbaticals is innovative, and provides opportunities for additional training of Swedish investigators. Taken together, this is a very competitive application that will contribute to the understanding of diabetes and its complications and potentially lead to new treatment modalities as well as improvements in the ability to predict the disease. This group of investigators is extremely competitive internationally and they are well positioned to make important future advancements. However, one major concern needs special attention. As presented, the research proposal is overly ambitious, to the point of appearing unrealistic. Along these lines, the application would have greatly benefitted from a more formal presentation of program priorities, including a more clearly defined organizational and management structure. Beredningsgruppens yttrande VR-St-Dia, Eriksson, Per Filip Billy

11 Dnr Efternamn, Förnamn Fredman, Pam Göteborgs universitet Bidragsform Strategiska forskningsområden Projekttitel Bekämpa typ 2 diabetes och dess komplikationer - etablera ett stategiskt forskningscentrum inom diabetes i Västsverige (DiaWest) Ämnesområde/målområde Medicin Beredningsgrupp Diabetes (VR-St-Dia) Evaluation form Strategic research areas panel evaluation 1. Evaluate scientific quality by international comparison (scale:1-5) based on: A) - scientific quality. B) - potential development of the scientific environment. C) - how the area is prioritised among the applicant s activities to generate the conditions for scientific excellence. D) - strategies to increase Sweden s international scientific competitiveness in the research area. Assessment note: The application focuses on the treatment and prevention of type 2 diabetes and proposes the following focus areas of research: 1) Understanding the role and mechanism of the gastrointestinal tract in improving type 2 diabetes following bariatric surgery. 2) Further develop the new therapeutic targets identified, i.e. SNAP23, FOXC2 and WISP2 as potential treatments for obesity, inflammation and diabetes. 3) Prevention and understanding of ectopic lipid accumulation, inflammation, cardiovascular and renal complications in relation to obesity and type 2 diabetes. 4) Initiate a prevention trial designed to see how life style changes might alter the course of type 2 diabetes. Supporting activities include: 1) development of drug targets potentially identified above together with mainly AstraZeneca, 2) Establishment of a state-of-the-art phenotyping laboratory for clinical studies allowing characterization from genotype to phenotype and 3) Establishment of research and career development programs in diabetes. The scientist comprising the proposed research consortium has for many years been in the forefront within the research fields proposed and already made significant contributions thus building further on a strong platform and expertise. In addition the composition of scientists should promote translational research, since within each area, a mix of clinical and mechanistic research is proposed. Furthermore, they can expand and build on a well established patient population including: Swedish National Diabetes Register (NDR) including 220,000 patients and established in UGOT/VGR, and Swedish Obese Subjects (SOS) an ongoing, prospective, controlled intervention trial involving 2,010 obese subjects who underwent bariatric surgery and 2,037 matched obese controls conventionally treated in the Swedish primary health care system. The clinical material/expertise could have been better utilized in the application, by encompassing additional areas of diabetes research. For example, the investigators appear to have missed the opportunity to use the same technology platform to examine other aspects of diabetes such as the gastrointestinal tract in type 1 diabetes, beta cells, insulin secretion and insulin resistance in a setting of autoimmunity. Lastly, the overall aim to reduce type 2 diabetes and its complications by at least 25% within 10 years, although laudable, is not substantiated as a realistic goal. 2. Evaluate strategic importance to the business sector and society (scale: 1-5) based on: A) - why, and in what way, the research area is, or can become, strategically important for the business sector and society. B) - strategies and plans to generate benefits from research findings in the research area. C) - capacity and supportive activities to generate benefits from research findings in the research area. D) - engagement and participation of the business sector, industrial research institutes, and other community organisations in problem formulation and implementation. Assessment note: One of the major collaborators of this group at the present time is AstraZeneca. However, few specific details on the collaboration are provided. The applicants propose joint postdoc programs, but these are insufficiently detailed to adequately judge whether this approach is likely to be fruitful. Formal alliances with other academic and industrial institutions - both national and international - are to some degree missing, thereby not realizing the full potential for development of the scientific environment. The investigator team has already shown that it can capture the benefits, e.g. approximately 100 papers have been published based on the data from the SOS study. Furthermore, the investigators have made a high bibliometric impact, a factor that will strongly facilitate communication and distribution of research results. Taken together, the proposed research and clinical trials have the potential to significantly impact the way we treat diabetes in the future via the identification of new treatment modalities and identification of new drug targets. However, the approach is limited both in terms of scope and in national and international collaborations. Thus, the applicants are missing an opportunity to fully explore the potential of the proposed research and to develop the field of diabetes more broadly.

12 3. Evaluate the need for infrastructure - The need for infrastructure is not a criterion for assessing the application s quality, but the comments highlight the infrastructure that currently exists and that which needs to be financed to enable implementation of the proposed research programme. Comments: The investigators plan to hire one top researcher and 2-3 young lecturers or professors, and to develop a research assistant program, a postdoc program and a PhD school in diabetes. Furthermore, the investigators plan to establish a phenotyping core facility to utilize the large number of patient samples available. This proposed core facility would provide state-of-the-art expertise in stable isotopes and upgraded equipment for assessment of insulin sensitivity and secretory capacity, body composition, endothelial function and vascular imaging technologies. It is assumed that the expensive equipment" requested is for the establishment of this facility but this is not clear and should be addressed in more detail. Otherwise the infrastructure of the proposed center utilizes the excellent existing infrastructure at the Gothenburg University. 4. Overall grade (scale:1-5) 3 (1=Insufficient, 2=Good, 3=Very good, 4=Excellent, 5=Outstanding) The panel s summary of the application s quality in relation to the criteria listed above. This is a competitive and innovative application that will contribute to our understanding of obesity, diabetes and its complications, and cement Sweden s leading role within the research fields proposed. Furthermore, it may result in identification of new treatment modalities and identification of drug targets to treat diabetes and its complications, e.g. 1) via the development of better and more safe procedures for gastric bypass, the only known cure for type 2 diabetes, 2) via an understanding of the underlying mechanism of gastric bypass on obesity and type 2 diabetes so that no surgical procedures can be developed to mimic the effect and 3) via a further biological understanding/validation of the proposed targets. The primary intervention study in type 2 diabetes may facilitate better treatments for the disease. However, the approach is limited both in scope and in terms of national and international academic and industrial collaborations, thereby missing an opportunity to fully explore the potential of the proposed research and to advance the field of diabetes. Beredningsgruppens yttrande VR-St-Dia, Fredman, Pam

13 Dnr Efternamn, Förnamn Millnert, Mille Linköpings universitet Rektor Bidragsform Strategiska forskningsområden Projekttitel Prevention av diabetes och dess komplikationer Ämnesområde/målområde Medicin Beredningsgrupp Diabetes (VR-St-Dia) Evaluation form Strategic research areas panel evaluation 1. Evaluate scientific quality by international comparison (scale:1-5) based on: A) - scientific quality. B) - potential development of the scientific environment. C) - how the area is prioritised among the applicant s activities to generate the conditions for scientific excellence. D) - strategies to increase Sweden s international scientific competitiveness in the research area. Assessment note: The general aim of this application from Linköping University (together with Stockholm University) is to coordinate the resources and competencies in diabetes research for prevention and treatment of both type 1 and type 2 diabetes (T1D and T2D, respectively) and their complications. To accomplish these goals, the investigators have presented a variety of loosely linked projects. For T1D they focus on the use of GAD vaccination as a treatment to prevent disease, ethical issues with respect to screening and prevention, protein arrays for better screening protocols, and the role of stress and viruses in the pathogenesis of T1D. For T2D, they present projects on insulin signaling/insulin resistance with mathematical modeling, the study of adipocytes from overfed subjects, the role of islet amyloid polypeptide on islet survival in a transgenic mouse model, the differentiation of brown adipose tissue, and mitochondrial processes in aging in mtdna mutator mice. For prevention of complications, they combine access to long-term study populations, such as VISS (study from 1983 for vascular complications in diabetes- which will help define parameters of glucose control), and Cardipp (study found nocturnal hypertension in diabetics), study of vascular physiology, and studies of IGF. They intend to develop web-based applications for improved patient education. The strengths of this consortium are the involvement of pediatric research, in particular the commitment to clinical trials, and its access to long-term cohorts of subjects. The program involves internationally recognized investigators. However, much of the program relies on the use of existing patient cohorts to simply add minor ancillary studies rather than creating novel research programs. Moreover, much of the proposed work lacks specific detail and it is therefore unclear whether the expertise and scientific approach is sufficient to make significant advances. For example, none of the investigators have special expertise in studying the role of stress in type 1 diabetes, the expertise in immunological studies is not profound, there is no detail provided in the design and analysis in the modeling approach to insulin resistance, and no indication of how findings will be tested in animal models is included. The GAD vaccination is an important achievement and component of the project, but again, the investigators fail to consider how the findings could be complemented with other approaches and do not anticipate the possible lack of a positive outcome. Besides, there was an additional ethical concern raised involving the proposed use of pancreatic biopsies in human subjects. A more novel project includes the differentiation of brown adipose tissue, but no details of what will be investigated are provided. Overall, the combination of researchers has potential, but there is little strategic unification and networking either within the consortium or with other institutions. Furthermore, little detail is provided of how the science will be accomplished, dampening the enthusiasm for this application. 2. Evaluate strategic importance to the business sector and society (scale: 1-5) based on: A) - why, and in what way, the research area is, or can become, strategically important for the business sector and society. B) - strategies and plans to generate benefits from research findings in the research area. C) - capacity and supportive activities to generate benefits from research findings in the research area. D) - engagement and participation of the business sector, industrial research institutes, and other community organisations in problem formulation and implementation. Assessment note: There is potential for developments with industry (eg Diamyd, protein arrays, drug development), but unfortunately, there is limited information about relationships with industry. The application fails to address this component, simply providing a general description of LiU Innovation which is essentially a technology transfer office, but no specific details are provided. 3. Evaluate the need for infrastructure - The need for infrastructure is not a criterion for assessing the application s quality, but the comments highlight the infrastructure that currently exists and that which needs to be financed to enable implementation of the proposed research programme. Comments:

14 No immediate infrastructure needs are highlighted. Indeed, apart from a need for a new Biacore instrument, the investigators state that there are no infrastructure needs. Moreover, there are few details provided on how funding will be used for new research groups or investigators, training programs, or how to increase high end technology or human resources in Sweden. 4. Overall grade (scale:1-5) 2 (1=Insufficient, 2=Good, 3=Very good, 4=Excellent, 5=Outstanding) The panel s summary of the application s quality in relation to the criteria listed above. Overall, the combination of researchers has potential, but there is little strategic unification and networking within the consortium or with other groups outside the consortium, and little detail of how the science will be accomplished, dampening the enthusiasm for this application. Beredningsgruppens yttrande VR-St-Dia, Millnert, Mille

15 Dnr Efternamn, Förnamn Wallberg-Henriksson, Harriet Bidragsform Strategiska forskningsområden Projekttitel Program för translationell diabetesforskning, utbildning och vård Ämnesområde/målområde Medicin Beredningsgrupp Diabetes (VR-St-Dia) Evaluation form Strategic research areas panel evaluation 1. Evaluate scientific quality by international comparison (scale:1-5) based on: A) - scientific quality. B) - potential development of the scientific environment. C) - how the area is prioritised among the applicant s activities to generate the conditions for scientific excellence. D) - strategies to increase Sweden s international scientific competitiveness in the research area. Assessment note: This proposal is a consortium of Principal Investigators from both the Karolinska Institute and Umeå University. This talented group of senior Principal Investigators has a long-standing and internationally recognized track record of excellence in diabetes research, largely in the area of Type 2 diabetes. Investigators from the Karolinska Institute are predominant in the application and this Institute is clearly a world leader in the field. A variety of comparative/literature citation metrics data provided strongly support this view. Both the physical and academic infrastructures of this consortium are already quite well developed. The research environment is outstanding and is considered to be state-of-the-art for supporting ongoing diabetes research ventures. Importantly, several of the Investigators are physician scientists who are clinically active, greatly positioning this group to perform genuinely translational research that is a major goal of the program. The proposal clearly documents the involvement of the research community in bridging basic and clinical research activities. The consortium will complement an EU-based initiative (www.eatris.eu) to create a complete infrastructure platform for translational research involving all core facilities at the Karolinska Institute including a dedicated and centralized clinical research center focused on metabolic aspects of diabetes and its complications. The consortium will be supported by a BIOBANK to assist investigators in large-scale sample and data collections, a non-commercial core facility for academic and health care-related research, with large collections of samples from patients with diabetes and its complications, by the Karolinska Genomics Core Facility which offers a broad range of genomic methods for studies of health and disease based on Affymetrix, Illumina, Sequenom and Applied Biosystems (ABI) technologies. The quality of the faculty, their outstanding research record and the excellent facilities all contribute to making this an outstanding proposal. There are other areas of strength described in the application that warrant support for the program. There is a strong management plan presented that increases the confidence that program goals can be achieved. Also, there is an excellent description of both technology and training platforms to be developed in this group. In particular, there was strong support for the development of an international virtual classroom for the study of diabetes with established collaborative agreements with some of the best the best academic institutions in Europe and North America with outreaches extending to Universities in Africa, China and Singapore. There were two primary concerns regarding the applications. One apprehension with this program is the overarching emphasis on Type 2 diabetes research. While the proposal repeatedly mentions Type 1 and Type 2 diabetes research, there is little documented experience in this group in translational studies in autoimmune, type 1 diabetes (with the exception of Dr. Annika Tibell). In general, there is little distinction made in the proposal between Type 1 and Type 2 diabetes. The proposal mentions islet transplantation studies and using new immunomodulating agents to prevent Type 1 diabetes, but there is little explanation of how such programs will be supported. This is important due to the very high relative risk/incidence of Type 1 diabetes in the Swedish population. There was an additional concern raised on how the initiatives developed in this program intersect with and/or augment current major national and international consortia, especially regarding gene/protein screening programs. It would be of general benefit for this group to outline how their program will provide added value to other existing programs in this research area. 2. Evaluate strategic importance to the business sector and society (scale: 1-5) based on: A) - why, and in what way, the research area is, or can become, strategically important for the business sector and society. B) - strategies and plans to generate benefits from research findings in the research area. C) - capacity and supportive activities to generate benefits from research findings in the research area. D) - engagement and participation of the business sector, industrial research institutes, and other community organisations in problem formulation and implementation. Assessment note:

16 There is no doubt that a major initiative in diabetes research is strategically essential for both the business sector and the society in general, especially in Sweden where diabetes is a major health care concern. This Karolinska/Umeå consortium is well positioned to translate discovery-based research to clinical trials. The program described is largely focused on high-throughput technologies and corresponding data informatics to result in new gene/protein discovery. The major goal is to use these data to identify reliable biomarkers for diagnostic purposes and/or to develop new therapeutic targets for disease prevention and treatment. This group is especially well positioned to connect this basic research with business/industrial entities to promote clinical studies. In particular, the Karolinska Institute has a very well developed infrastructure to execute this program and there are clear Institutional commitments to further enhance the research environment. This group already has strong industry support and a clear bench-to-beside algorithm is described in the proposal. Noteworthy is the range of onsite industrial partners, from established pharmaceutical to smaller start-up biotechnology companies. The academic/industrial connection is viewed as highly competitive on the international level to develop new diagnostic and therapeutic agents for clinical use. 3. Evaluate the need for infrastructure - The need for infrastructure is not a criterion for assessing the application s quality, but the comments highlight the infrastructure that currently exists and that which needs to be financed to enable implementation of the proposed research programme. Comments: The Karolinska/ Umeå consortium is supported by an outstanding and state-of-the-art research infrastructure. There are major current and planned commitments by the Karolinska to further enhance the research capacity relevant to this program. Importantly, the current infrastructure strongly supports both basic and clinical research activities outlined in the proposal. The requested budget is appropriate for this program: equipment to support the high-throughput gene/protein analysis and corresponding data analysis are considered essential. There is also a major budget allocation for graduate/ postdoctoral fellow training, young investigator support, and recruitment start-up packages. This building of academic strength is at least as essential to the building of physical infrastructure and is strongly supported to provide ongoing and future scientific vitality to this research community. Support for both Scientific and Innovative Advisory Board travel is a minor but important and appropriate component of the budget request. 4. Overall grade (scale:1-5) 4 (1=Insufficient, 2=Good, 3=Very good, 4=Excellent, 5=Outstanding) The panel s summary of the application s quality in relation to the criteria listed above. Overall, this group is a highly productive and internationally excellent group to promote translational diabetes research. There is some concern that Type 1 diabetes programs will not keep pace with the outstanding Type 2 diabetes programs. Beredningsgruppens yttrande VR-St-Dia, Wallberg-Henriksson, Harriet

17

18 Slutgiltiga yttranden Expertpanelen inom Effekter på naturresurser, ekosystemtjänster och biologisk mångfald

19 Effects on natural resources, ecosystem services and biodiversity Nr Applicant Kåre Bremer, Stockholm university Title A multiscale, cross-disciplinary approach to the study of climate change effects on ecosystem services and biodiversity Statement Scientific quality This proposal advances scientific ideas that are at the forefront of ecological ecosystem research and the capacity to undertake such research is not questioned. The coverage of the main natural science themes is good. A number of interesting and currently relevant topics have been outlined, and they include the linking of ecosystem services with underlying mechanistic processes relating to ecological community traits and interactions, and considering the impacts of climate change on these interaction and ecosystem level networks. This proposed research is then set within an adaptive management context, with a view to applying new ecosystem knowledge to improve land management solutions. There is emphasis of modeling complex social and ecological systems. The quality of the scientific work is likely to be high based on the established reputation of the applicants. However, this is not immediately apparent from the proposal, as little detail is given on modeling approaches or empirical procedures. While the overall goals are good, the detail provided in the proposal is not particularly convincing. The proposal rarely gets beyond an abstract description of objectives. Mention of coupled socio-economic systems, adaptive management and functional trait approaches conveys little more than an overarching framework by which to proceed. The research is driven primarily by focused scientific curiosity rather than a clear recognition of the need to address societal challenges. Thus there is a very heavy ecological focus to much of this proposal that does not obviously respond to fulfilling major needs and solving important problems in society in any direct or immediate way. The scientific outputs may well be high, even potentially outstanding, but the societal impact is more questionable. The section on social behaviour is weak. There is discussion of how social behaviour contributes or detracts from the resilience of ecosystems (page 11), but the other loop of the feedback how changes in environment affect social behaviour is apparently not considered. There is little mention of how social behaviour might be influenced by the policy or economic environment. The adaptive governance theme focuses on the failings of governance, with no consideration of learning from the successes. Policy is considered as a top-down government led approach, but there is little consideration of the many forms of governance at local and district levels. Strategic importance This proposal is driven by the desire to provide a clear mechanistic understanding to the likely environmental and related ecosystem service impacts of climate change. It further seeks to use such understanding to improve the society s response to these challenges, particularly through

20 the adaptive management approach that recognizes the coupled nature of ecological and social systems. The vision does not include much in the way of public outreach and involvement of various societal elements, either in shaping the research programme, in providing socially relevant information, or as decision makers and ultimate beneficiaries. Connection to the Swedish business sector is very weak. Indeed much of the research is strongly academic in focus and there has been little attempt to establish links with business, land management or policy institutions. Policy and economic dimensions are weak throughout the proposal, and where they are considered it is in an abstract and theoretical manner. Outreach and information dissemination is targeted mainly to the academic world through journal publications. Mention of public seminars is included, but this does not seem to be in addition to existing pathways. Overall assessment The applicants represent an excellent group of scientists who are highly regarded internationally and have made substantial contributions to their respective fields. The proposal is driven by an ecological imperative with societal and strategic considerations given little weight, in contrast to the terms of reference as stated in the guidelines. The panel recommends this proposal to be funded with residual funding. Overall assessment: grade 3 Very good

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