RICERCA ITALIANA     

Centre for Bio-molecular Interdisciplinary Studies and Industrial Applications (CISI).

Università degli Studi di Milano

Abstract

1.The mission of the Centre for bio-molecular studies and industrial applications (CISI) will be to promote and co-ordinate research, technological development, and training activities of scientific and economic interest. Such definition of the mission of CISI closely follows the recommendation of the EU, the Italian Government and the Ministry of University (MURST). It is planned that CISI through the implementation of two key technological platforms (DNA chip technology and development of methods for combinatorial synthesis and high throughput screening of compounds with biological activity) will collaborate with a selected group of 12 industries on: assisted selection in crop species, specially relevant to Italian agriculture; DNA/RNA probe diagnostic systems for the medical and veterinary sciences; development of advanced scientific instrumentation based on Nucleic Acid Technology (NAT). These areas of activity are closely interconnected since they are based on: common scientific background, provided by a large group of scientists of international level; similar methodological approaches; state of the art of genomic studies in plant, micro-organisms, and humans, and a carefully planned strategy of industrial development.

2. Human and financial resources available to CISI will be: four groups of internationally known scientists and scholars from the medical, veterinary, chemistry and agriculture faculties of Milan University; the R&D personnel of 2 multinational (Chiron, U.S.A. and Lepetit- Aventis, Germany) and 10 Italian biotech industries; a total of 50 Ph.D. students from five Ph.D. schools in life sciences of the University of Milan; 3 four years fellowships, and an initial contribution totalling ca. $ 2,300,000 from private industries and a non profit foundation. Such resources will add to the support provided by the Milan University and MURST following this application. It should be added that all salaries of permanent staff and scholars of the University of Milan, overheads and laboratory spaces and basic equipment will be paid by the University of Milan.

3. CISI will be directed by Prof. F.Salamini, an outstanding scientist, plant genetist and biochemist, full professor of Milan University (on leave of absence) presently Director of the Max-Plank-Institut fur Zuchtungsforschung of Cologne (Germany), flanked by an international scientific board, with Prof. Renato Dulbecco, Nobel prize for Medicine as President.

3. The programme of activity of CISI will be divided in three temporal phases, spanning a five years period, after which, according to recommendations put forward by the "National Programme for the development of Biotechnology of Italy" and the MURST is expected to spin off as a separate, independent entity. <<<

Principal Investigator

Francesco SALAMINI Università degli Studi di MILANO

International Relationship

2.4 The interaction between CISI and other research and business-oriented institutions.

The V EU framework program of research has been mainly directed to promote the interaction between public research institutions and industry. The need for a more close collaboration between these two entities has also been stressed by the report on biotechnology of the Office of the Italian Prime Minister which has been previously cited (see section 2.2.1). The lack of collaboration, however, is not, by all means, the main obstacle for the development of biotechnology in Italy. One can note that research funds available for all areas of research are very scarce since Italy spends only a little more than 1% of its GIP in research, as compared with 2.8% in the U.S.A. and other major industrialised countries. In addition, research money is mainly funnelled into traditional "hard sciences" like physics. Italy is also notable for the almost complete absence of private risk capital invested in biotechnological companies. Thus the collaboration between public research and industry is not easy to achieve in this field, and it is not surprising that the Italian government is so keen to increase the interaction between industry and the largely unexploited intellectual capital of Italian Universities. A similar action, which has been recently promoted by the German government through a programme named BioRegio, has met with extremely encouraging success, since it has spun off a large number of companies stemming from the collaboration between University and the private sector. The programme outlined in the present proposal is aimed to set an example of how a substantial collaboration between an interdisciplinary group of university scholars and scientists and a group of 12 industries active in biotechnology can be organised. The key to a successful interaction is to centre on the "core business" of the industries which participate in the programme. A too-advanced research activity may, in fact, give rise to products for which an industry has no market. As such, it is likely that the same industry will not commit to such a programme a substantial part of its R&D research resources. Thus a preliminary, substantial effort has been made to precisely define the type of products industry thinks that should be developed and what kind of scientific background would be required for its development. A good deal of effort has obviously been made by scientists with experience in the development of advanced instrumentation to refine initial ideas and to analyse the technical capability of the interested industrial partner. By careful matching of various factors, a satisfactory preliminary programme could be defined. Is is relevant to point out that following this first step the 12 industries involved have agreed to finance a total of 18 Ph.D. salaries, providing an investment of about $800,000 in the project. In addition, they have made available a significant fraction of their R&D resources to pursue the commonly shared work objective.

It now seems useful to spend some time on the description of the R&D activities of the industrial partners of this venture. For the agro-food area, collaboration relating to technological development and transfer to the final users will be obtained through collaboration with the Fondazione Parco Tecnologico Padano and its operative branch, CERSA. The foundation has already provided 3 research fellowships and $500,000 for each of the next three years as seed money. CERSA, through its laboratory of "plant and animal genome markers" will transfer the results obtained by CISI to breeder and grower associations. As regards Chiron S.p.A., it is the Italian branch of Chiron U.S.A., a well-known biotech company. Lepetit S.p.A. is 100% controlled by Aventis, Frankfurt. The company has large fermentation plants in Italy and it is noted for its discovery of rifampicin and other key antibiotics. Biosearch S.p.A. is a spin off of Lepetit and is active in high throughput screening and lead optimisation of biological compounds. It has a library of more than 100,000 compounds. Quanta System s.r.l. is a spin off of C.I.S.E., Milan, and is a leader in Italy in the development and application of laser techniques. Inpeco s.r.l. is a leader in the area of laboratory automation. It is working under contract for the development of advanced instrumentation for Beckman, U.S.A., Ortho, U.S.A., Olympus, Japan, and Glaxo, U.K. Angelantoni Industrie S.p.A. is an internationally based industry leader in criogenic technology. Clonit s.r.l. is the only Italian industry with a substantial production and development activity in DNA/RNA-based diagnostic kits. Areta s.r.l. is the only Italian company dedicated to the development and production of human monoclonal antibodies. It has dedicated ISO 9002-certified laboratories for the production of biologicals for parenteral use. Further information about other companies involved in the project is given in section 2.1.5.

In addition to the previously cited companies, the Centre will capitalise on the network of existing collaboration between each participating group from Milan University and colleagues abroad. For example, a substantial collaboration in the bioinformatic area will be obtained through Dr. Bishop of the Sanger Institute, U.K. Finally, It is relevant to point out the existing collaboration between Milan University and the Istituto di Tecnologie Biomediche Avanzate of the Italian National Research Council. This collaboration will be particularly important in the areas of mass spectroscopy, proteome analysis, DNA sequencing and in the development of scientific instrumentation. <<<

Research Objectives

2.2 Development, research, and organization of CISI, an Interdisciplinary Centre of Studies and Industrial applications.

2.2.1 Objectives.

The EU report on competitiveness of biotechnology in Europe (De Looze et al., Eu-CT 942032, 1996) has stressed the need for the European countries to promote biotechnology by an increase in the collaboration between public institutions and industry. In fact there is a major difference between Europe and U.S. in this field. Whereas Europe seems to be on the same level as the U.S. for the quality and strength of public research, the capability of developing extensive clinical studies and its potential market of more than 260 million people, the existence in the U.S. of a strong interaction between industry, government and University institutions, supported by a large amount of risk capital, has determined a gap between the two countries in the number and in the commercial value of biotechnology products on market. A similar report by a National Committee nominated by the Italian Prime Minister (1999) to provide suitable indications for the development of biotechnology in Italy has proposed the institution of a number of R&D "centres of excellence in biotechnology" as a major driving force to foster the development of this field in Italy.

Milan is the major industrial centre of Italy and the capital of Lombardy. In Milan there are 2778 companies operating in the agro-industry, 445 in the environmental and 2561 in the pharmaceutical field, whereas the University of Milan ranks first among Italian universities for scientific productivity (Science citation index). Thus in this geographic area there is a unique opportunity for the successful operation of a well﷓organised R&D centre dedicated to biotecnology and based on the collaboration between Industry and University. The proposed centre (CISI), which is described in this application, will operate according to the previously reported recommendations and will initially benefit from a specific financial support of the Ministry of University and Scientific Research, (MURST). It is required, however, that later it should "spin off" as a separate, independent entity. Thus the centre will not only focus on scientific merit and excellence of research, but also on the capability of attracting the interest of private companies for the development of innovative products of commercial value. In short, CISI will operate in two major areas of interest. Agro-food and biotechnology-based probe diagnostic systems, through the implementation of three major technological platforms i.e. genetic arrays/DNA chips, combinatorial synthesis/high throughput screening of chemical compounds, development of fully automatic methods of analysis based on the rapidly advancing DNA/RNA knowledge of biological systems. These different aspects are very closely interconnected as regards the scientific background required, common molecular technologies, coherent industrial interests, and need for advanced training of young scientists. CISI will specifically: 1) coordinate and execute specific R&D projects in collaboration between internationally qualified scientist, Ph.D. students and industrial investigators of 12 multinational and SMI private companies; 2) develop advanced products and prototypes suitable for industrial exploitation; 3) make available to other interested parties the skill, experience and the large instrumentation of the centre for the development of collaborative R&D research; 4) develop an interdisciplinary program of Ph.D. training and research in life sciences.



2.2.2 Organisation of CISI

According to the guidelines provided by the Italian government, the new "Centres of excellence" in biotechnology, which will be identified following a national selection from a number of proposals made by Italian Universities, after an initial three-year period (during which their financial support will be provided by the Government and by a local University), should develop into self-supporting, independent entities. A series of laws recently approved by the Italian Parliament have provided the necessary framework to allow scholars and researchers from public institutions to "spin off", in collaboration with industry, private, and independent industrial enterprises. The transformation of CISI after the first three years of operation under public control into an independent body will require a careful planning since no previous example of this kind has yet been available in Italy. It seems clear that the successful operation of this venture, whose program of activity and organisation is outlined in this proposal, very closely depends on the establishment of a fruitful cooperation between university scientists and the 12 industries which will participate, from the beginning, in the set-up and operations of the centre. This section will only outline the general organisation of the centre during the initial three-year period, since other sections of this report will specifically deal with other aspects of interest.

(i)Location. The administrative and directional activities of CISI will initially be located in offices made available by the University of Milan. Given the short time allowed to start operations and the limited funds available, the R&D work activities will initially be carried out either in the University or in the industrial laboratories already available. In the second planned phase of activity, CISI will acquire separate headquarters, where major instrumentation will be located.

(ii)Direction. Prof. F. Salamini will be appointed director of CISI F. Salamini is an outstanding scientist in plant genetics and biochemistry; he is presently full professor at the University of Milan (on leave of absence) and Director of the Max-Planck Institut fur Zuchtungsforschung in Cologne (Germany). He will be supported by a Scientific Committee chaired by Prof. Renato Dulbecco, Nobel prize for Medicine, and including 5 scientists to represent the main areas of scientific activity of the centre, 2 members chosen by the participating industries, 3 high-level independent scientists, and one member representing young scientists undergoing training. The technical and administrative duties of the centre will be carried out by two full-time people to work on administration and a high-level technical person having a well-documented experience in the management and direction of industrial research. The stipends of these people will be paid by Milan University.

(iii) Personnel. A number of scientist and scholars of Milan University will be associated part-time in the research activities of the centre. A major part of the experimental work, however, will be carried out by two groups of people. The first group (10 scientists) will have four-year research contracts fully paid by the Milan University. They will be chosen from among young promising post-doctorate scientists having at least three years of research experience. Five of them will be required to have spent at least three years working in universities or research laboratories abroad. A second group will consists of Ph.D. students enrolled in 5 Ph.D. life science and chemistry programs of Milan University. It should be pointed out that a total of 18 Ph.D. positions will be financed (about $800,000) by the 12 industries partcipating in the initial R&D programs of the centre, whereas Milan University will provide an additional $1,400,000 to support 32 Ph.D.s for a three-year period in the centre. In addition, another three 4-year research contracts to be held by established scientists will be made available by the Fondazione Parco Tecnologico Padano (Cersa), which will collaborate with CISI on research projects centreed on animal and plant marker-assisted selection.

In conclusion, CISI will be staffed by a qualified medium-sized work force which will be fully able to reach the objectives of the R&D programs outlined in the previous s... <<<