In the context of the current proposal we define the yearly intermediate reports as milestones because the reports will reveal the success of the implementation of the project as measured by the achieved results against the respective plans. Thus, a milestone, in the sense of the current guide, occurs and decisions regarding any changes in the implementation of the project can be made if specific shortcomings are reviled.

B2 Implementation

The project management will be implemented strictly within the management structure of the EBC. Therefore we shall start with a brief description of the latter. The ground rules of the management of EBC are fixed in its Statute, which is approved by a special Decree of the Estonian Government. The EBC is accountable to the Government via Ministry of Education and Science. Changes in the structure of the EBC, approving its budget and electing researchers is the responsibility of the Scientific Council. Scientific council is the ruling body of the EBC. Its role is in developing, discussing and approving RTD directions of the EBC, basic changes at the organisational level etc. Out of nine Scientific Council members, 6 are elected by research stuff. Three outside members, chosen among leading Estonian researchers of close fields, are also the voting Members of the Council. The Council is responsible for approving budget, research directions and electing researchers. Director (important: according to Estonian legislation, director of a research institution is a research, not administrative position) is elected by the Council for a 5 year period, which is renewable. Director's responsibility is in co-ordination and in representing the EBC.

Altogether, administration of the EBC includes 3 people: chief accountant, personnel clerk and managing director. The latter is responsible for organising the work of the supporting staff, management of the building etc.

The EBC has an International Advisory Board (AB). AB is not strictly academic, but covers different expertise. Recommendations of the AB are discussed in our Council and taken into account wherever possible. We may add here that some members of the AB visit EBC more than once a year and many of the staff members are in regular scientific correspondence with one or other AB member.

Management of the project

The management structure of the project is outlined on diagram 2.1.1. A full time manager will be hired to manage the day-to-day business of the project. The manager will be responsible for i) keeping the overall progress of the project on track, ii) will advise and help the research group leaders with organisational questions regarding to the activities envisaged under WP2 and WP3 and WP4. The manager will also collect reports from all grant awardees of different grants and stipends of the project and participants of D5.1 and the managers of D5.1 and D5.2. These reports serve as constituents for the intermediate and final report to the Commission and as feedback to the manager himself and the council in endorsing changes to the implementation of the project if needed. The manager will also be responsible for writing the yearly intermediate and the final report of the project which will be approved by the council and signed by the director. The manager will be working directly under the supervision of the director of the EBC who will, in turn, follow the guidance and endorsed policy of the scientific council. Major decisions such as approvals of applications for grants will by taken on the scientific council level (or by a panel nominated by the council). In addition, three part-time managers will be hired who will be responsible for organizing the i) yearly GENEFORUM conference, ii) 3 (one per year) hands-on courses / seminars on post genomics tools and iii) 3 (one per year) hands-on courses / seminars on genome analysis. In WP 1 the EBC council will nominate a selection panel of 4-5 persons who will be in charge of the women in science grants. They will formulate and announce the in-house call and select the applications that will be financed. For the repatriation program the EBC council itself will serve as the selection committee. In- and outward mobility actions will be initiated at the research group level and brought to the EBC council for approval. The manager will help the applicants with the applications.

The manager will keep track on the progress of the project continuously and upon any major deviations will consult the director. More detailed analysis of the proceeding of the project is performed during the intermediate reporting to the Commission. Any problems or deviations that may occur will be brought to the council by the director. The council may opt to solve the issue with consultations with the respective research group(s) and/or seek additional advice form the International Advisory Board who will receive also the copies of the intermediate reports.

B.2.2 Beneficiaries

The Estonian Biocentre (EBC) was established in 1986 as a joint venture between the Academy of Sciences and University of Tartu, in order to promote basic and applied research in gene and cellular technologies in Estonia via research and human capital development. It is a legally independent non-profit research institution, though operates under twinning agreement with the University, in particular its institute of molecular and cellular biology. EBC participates in university teaching in all levels, ending with PhD studies and post-doc training. The research staff of EBC is about 75 people, including part-time employed research students. The current main research direction of EBC is focussed to human genomics and bioinformatics, including inter- and transdisciplinary studies. EBC is the member of PG3 consortium. However, equally active is the ongoing research in environmental microbiology with a strong genomic component and in several applied directions, like vector design for medical purposes etc. The EBC runs also core facility for transgenic animals.

ISI Web of Science allows easy search for our present-day research potential, revealing in the relevant recent period of time (since 2000 till April 2007) about 2,600 references to about 185 research papers (see "Estonian Bioctr" under General Search, ISI Web of Knowledge) in the ISI-covered list of journals. It does not of course cover all publications, neither references to papers of individual researchers who have returned to Estonia more recently and have earlier publications under different (western) research institutions. Yet publications in Nature, Science, EMBO Journal, PloS Biology, long series of papers in the Am. J. Hum.Genet. and in many other top journals of particular research fields, document the quality of the ongoing in EBC research. This is in a large scale thanks to well-equipped modern research labs and group leaders of high international reputation. Estonian Biocentre has recently organized a core facility for genomics (DNA sequencing and genotyping). The latter is equipped with Illumina platform for complete genome genotyping and the current sequencing capacity, though moderate, allows in routine to sequence about 300,000 bp per 24 hours. This core facility is already used widely all over Estonian research groups, both academic and in SMEs, who need such techniques in their R&D projects. Researchers are also equipped by state-of-art cell sorters, imagers, RT-PCR, robotics for high-throughput research etc.

EBC became actively involved in FPs when it became legally possible under the PECO programme at the end of FP3. Success in FP4 and FP5 allowed further capacity building, including to carry out active repatriation scheme. EBC is among those few institutions who have achieved twice prestigious EC Centre of Excellence nomination (2000 and 2003) under the competition among that time "accession countries" - the present-day new member states. The quality of research can be also documented by more recent success in the participation FP6, carried out with no "custom-made" instruments for the new member states any longer operable. Here, EBC has participated and participates in 7 projects, including in a number of large-scale IPs in genomics and bioinformatics. Thanks to such intensive and already relatively long-lasting pan-EU collaboration, Estonian Biocentre has obtained some experience and capacity to plan and to carry out joint research programmes.. To end, it can be mentioned that we have already submitted, as a part of larger consortia, a few proposals into the first calls of FP7 - the outcome to be seen later this year.

In longer run, the major weakness we feel at present is in our too narrowly focussed strength, relying largely on high-tech genomics and related bioinformatics. Although not specified directly in work packages, EBC needs to build comparable capacity in metabolomics and, in a wider meaning, to re-generate/re-activate largely lost decades ago high-class knowledge in biochemistry and physiological chemistry. Though the term "systems biology" is currently often abused, it does bring together ideas for future developments.

B.2.3 Consortium as a whole

Not applicable

B.2.4 Resources to be committed

Indicative budget of the project is presented in Table 2.4.1. The support personnel costs of the project consist of stipends in WP2 and WP3, repatriate (WP1) and the instructors for the hands-on training courses / seminars salaries (WP5). Other direct costs under support are comprised of i) "women in science" grants; ii) travel & accommodation costs of study visits and brainstorm meetings (WP4), hands-on training courses / seminars and international conferences (WP5), and iii) consumables costs of the hands-on training courses / seminars and international conferences (WP5). Of these the "woman in science" grants deserve perhaps further attention. These grants are neither stipends nor salaries. In accordance with the work plan (see above) these grants serve the purpose of providing the applicants with the means of regaining scientific competence after the child-leave. The applicants write a grant proposal where they devise a work plan of their own. This may include attending conferences, hands-on courses, purchasing textbooks, study visits or similar. The appointed by the scientific council panel of in-house experts will evaluate the applications and decide upon financing based on the quality of the work plan and its ability to help the applicant achieve the goal of the WP - regaining scientific competence. The management personnel costs are comprised of the salaries of the general manager of the project and the salaries of the part-time managers of the hands-on training courses / seminars and international conferences.

The consumables costs for hands-on training courses / seminars (D5.1) and international conferences (D5.2) also need further explanation. In case of D5.1 we rest upon our now seven years of experience in organizing such courses and predict that on average one event will need approximately 20 000 EUR to cover the cost of consumables. The actual costs of a single event will vary depending on the topic if the course. The consumables budget for a course that spends considerable time on bioinformatics, for example, will be understandably smaller than that for a fully wet-lab based course. Another factor is the number of participants which also affects the consumables budget. Here we foresee that the number of participants in D5.1 will vary from 10 to 20 depending on the nature of the course. The bulk of consumables costs of D5.1 are made up from the costs of reagents (enzymes, etc) and solid labware. In the case of D5.2 we again have the opportunity to draw from our experience since the yearly Geneforum conferences started in the year 2000. We again calculate 20 000 EUR per event. Printed materials and facilities rent make up the bulk of consumables budget of D5.2.

In WP 4 we have declared travel & accommodation costs for study visits brainstorm meetings while there are no person/months listed. Here we provide two explanations for this potential discrepancy. Firstly, the study visits and brainstorm meetings will be short-time events. That prevents hiring people for that specific task. Secondly, all persons from the centre that will take part in either actions, will necessarily be employed by the centre anyway, covered by funding from other sources.

As already mentioned EBC is well-equipped research institute and by sharing facilities and equipment with its twinning institutions, does not seek for additional resources for research equipment under this call. The exception here is some additional capacity in some relatively low-cost instruments, specifically needed for the planned hands-on training courses. For these purposes we plan to obtain new sets of automatic pipets, small centrifuges and one PCR incubators, with a total cost of 60,0000 EUR. Our experience in such activities has shown us that although possible, it is both inconvenient and probably also somewhat unjust to "mobilize", for the courses, such an equipment from dedicated research labs. After all, good professionals, as everybody knows, hesitate to lend "their own" automatic pipets, lab-adjusted pre-programmed PCR incubators etc.
An additional sum of 4000 euros will be allocated for a workplace generation for the manager of the project.

At first glance the budget may seem unbalanced as so far as the different WPs are considered. Namely the funds allocated into WP5 comprise ca 40% of the total budget. However, when one considers the number of people involved in this workpackage (participants to the conferences and courses), the initial impression of unbalanced budget evaporates

B3 Impact

B.3.1 Strategic impact

The general list of expected impact of the REGPOT-2007-1, outlined in the Capacities Work Programme, is covered by our proposal in full. The four criteria: (i) upgrading the RTD capacity; (ii) better integration in the ERA; (iii) improved capacity as far as FP7 is concerned; (iv) better regional research capacity, are all addressed, often under different angles by a coherent set of measures. Below we comment several aspects of the expected impacts in some details.

The main expected impact of the proposal for EBC is in enhancing its research quality, measured here through directly verifiable indicators, primarily by submitted joint proposals in different FP7 calls and published in high-class international journals papers. To submit joint proposals anticipates, first and foremost, identification of common interest and complementary experience in a relevant to FP7 calls direction, specific complementary research resources and skills. It also needs trust. However, while complementary skills and overlapping interests can be largely searched by analysing publication records, trust comes slow and arises the best from joint research experience. This is why much attention of the proposed work programme is devoted to provide possibilities for joint research experiences. It starts from the opening to wider audience, both local and international, hands-on training courses, complemented by seminars and lectures. The next level here is providing means for PhD student exchange for several months. The final level are shorter reciprocal visits of experienced researchers - for seminars, lectures as well as providing time for in-depth scientific discussions, planning and evaluation of possibilities to collaborate, as well as already working on joint scholarly papers and, most importantly - on joint research proposals. It is hard to see how that can be achieved by local approach and because Estonia is a very small country, also in a national level.

Meanwhile, there are other and indeed national aspects to be considered and linked to the main goal(s). As explained elsewhere in this proposal, we need to find new skilled researchers as well as to mobilize un- or underused human resources. For the first, repatriation scheme is designed, but we stress here that its virtual equivalent is talent spotting and recruiting new people irrespective of their nationality. As far as un- and underused capacity mobilization is concerned, we primarily relay on our past very positive experience in providing means for women researchers, who have been out of science for a considerable period and who wish, but hesitate to return, to restore their competence and self-confidence.

We have indicated elsewhere in this proposal that the National Development Plan of Estonia, approved by DG Regio and instrumental for handling EC cohesion funds, specifies biomedical research as one of the priority areas, needed for long-time knowledge building and capacity in public health, whereas development of the same capacity is needed for the growing in Estonia biotech enterprises both in industry and medical service sector. Therefore, our proposal is well in line with expected impacts of the call as far as the mentioned economic and societal cohesion aspects are concerned.

The proposal lacks formal SWOT analysis. However, we do not wish to display our project as a win-win game in all its details, in particular in long run. There is human factor involved and good researchers are in high demand. Where possible, this can and should be foreseen by building certain parallelism in key knowledges and skills. We have such positive experience when we started to build up, some five years ago, professional team in bioinformatics.

B 3.2 Spreading excellence, exploiting results, disseminating knowledge

The mission of EBC since its opening has always included both goals: to enhance its own research capacity through increased excellence in research, and equally so not only disseminating know-how but also by "providing" new potential leaders and experienced researchers to different academic, in particular university labs as well as to the growing biotech industry in the fields and activities covered by EBC. For example, our successful earlier repatriation schemes have allowed to open not only new professorships in Tartu University, but to staff with several principal researchers the recently established Institute of Technology of Tartu University. We are particularly happy for the fact that several SMEs have been established by such repatriants and these spin-offs from our academic research are employing already many tens of specialists and that these SMEs have been as well successful in FP6. We trust that this balance can be achieved also during the coming years. The rationale here is that fast growth in public sector science, largely oriented to fundamental research, cannot be sustained unless the complementary private sector grows even faster. Estonian private sector in high- and medium-tech biotechnology is still in its rather early growth phase and can absorb many more people in different capacities, both in gene technologies and bioinformatics-data mining, and to grow its capacity in making profit, including via successful participation in FP7 calls and in establishing links over EU, including with pharmaceutical industry. We are well aware that there are many other calls within the FP7, facilitating the same pr, but we consider it worth stressing them also here.

In medium-long run, we believe in wider public benefit of the proposal, because the capacity we intend to build has in its focus also future needs of the successful use of the growing Estonian Genome Project, one of the main research-based cornerstones of the public health in future. Public health enhancement is a complex issue with many aspects. Probably only a minor part of it, in particular today, can be reduced to the advanced research in genomics and its post-genomic trends. However, it is a safe prediction that the importance of research achievements will grow and the least what this proposal would add is to facilitate, in short run, knowledge transfer needed for increased capacity in diagnostics and prognostics. Our recently gained experience with HIV genomics, drug-resistant tbc diagnostics and R&D-based improvement in diagnostics of several other infectious diseases, as well as establishment of DNA-based diagnostics of the main Mendelian disorders, is a proof that such an in-house, in the meaning of in-country, experience is highly valuable.

For immediate dissemination of project results a website will be opened. This site will serve as news board and archive at the same time. Upcoming events will be advertised and past events catalogued. Thus a constantly evolving "report" will be crated

Rapid dissemination of results, where appropriate, is also achieved thanks to the fact that EBC runs open for the whole community, core facility for DNA sequencing and genotyping. New developments in technologies, for example in data analysis, would be electronically transferred to partners and end-users of our network of labs.

Finally, close working contact with the National Contact Point for FP will allow pro-active analysis of coming calls well in advance to achieve an early alert of relevant research groups.

B4 Ethical issues

Our project is not directly linked to experimental research. Nevertheless, ethical issues are relevant also here. In short, Estonia has formulated and adopted a few years ago an Ethics codex for science. Secondly, Estonia is following the ground rules of the EU on the employment of scientists. Thirdly and more specifically, Estonia was one of the first European countries where the Parliament issued a special law regulating research in human genetic - this law was a pre-requisite to launch Estonian Genome Project, paying considerable attention also to personal data protection. Estonia has also signed EU rules for human stem cell research and they are binding in Estonia. All these legal norms and semi-voluntary rules are also followed in EBC. Relevant to work packages of this proposal, copies of the governing our research ethics rules will be handled to each of the new researcher coming either from Estonia or abroad. General institutional ethics committee (shared with Tartu University) is open for them for more specific questions. Our institutional Ethics Committee is not restricted to medical ethics, including lab animal handling issues, but covers research ethics in general. One may add that it is a binding rule that all Estonian grant proposals must address questions related to ethics, with special attention to those carried out in the field of biomedicine and clinical research.

B5 Gender aspects

We do consider gender aspects important and address these together with other measures that aim to the overall bettering of our human potential. The key issue here is fully mobilise and utilise our human resources and not specifically to endorse measures for artificial "equality". Women returning from child leave are in a position where they have stayed away from intensive scientific work for a prolonged time period. In order to facilitate their fast return into the competitive scientific environment where they can fully exploit their true potential and therefore benefit to the overall success of the centre, we have devised a special action under work package one "Mobilising Intellectual Capacity" - "Women in science" grant. These grants are neither stipends nor salaries. In accordance with the work plan (see above) these grants serve the purpose of providing the applicants with the means of regaining scientific competence after the child-leave. The applicants write a grant proposal where they devise a work plan of their own. This may include attending conferences, hands-on courses, purchasing textbooks, study visits or similar. The appointed by the scientific council panel of in-house experts will evaluate the applications and decide upon financing based on the quality of the work plan and its ability to help the applicant achieve the goal of the WP - regaining scientific competence.