Economic and social relevance
The knowledge infrastructure presently operating within the whole of the Netherlands is lacking in an organized and integrated Stem Cell and Developmental Biology strategy to obtain the fundamental knowledge that will ultimately lead to innovative applications in health and medicine. Indeed, the most powerful therapeutic approaches will come from our knowledge of the developmental signaling pathways operating in the determination of cell identity. Regeneration or replacement of defective, diseased or damaged cells will only be optimized by our complete understanding of developmental processes, stem cells and how the genetic program is regulated and maintained. Every day the international and national press is reporting on the potential use of embryonic stem cells in therapeutics and cloning. And just this past week an important step in the genetic manipulation (homologous recombination) of human ES cells has been achieved. We envision that the knowledge infrastructure will significantly contribute to novel therapies; for example therapies for thalassemia (which afflicts 2% of the world population), hypospadias (which afflicts almost 1% of newborn males in the Netherlands) and many other environmental and traumatic syndromes that can be treated by cell replacement therapies arising from ES cells, specific cell lineages differentiated from ES cells and from hematopoietic stem cells which may be manipulated to other cell fates. To keep the Netherlands in the forefront of Stem Cell and Developmental Biology and at the cutting edge in the application of these fundamental research results to health and medicine, the knowledge infrastructure must be supported.
The complexities of biomedical research into disease processes require a multidisciplinary approach; actively integrating developmental biology and animal models, stem cell biology and in vitro differentiation systems, molecular signaling and gene regulation. Expertise in these areas is spread throughout several major research universities/institutes in the Netherlands. At present, developmental research is mainly funded through the KNAW at one dedicated institute in the Netherlands, the Hubrecht Laboratory. However, there is no subsidy that will provide for the collaborations between these and other expert groups of developmental, stem cell and molecular biologists at the major Dutch research universities/institutes. Moreover, until Bsik there were no direct mechanisms to promote the implementation of fundamental research results to industrial applications, such as for example the production of molecules for intervention strategies in disease, development of model systems, and clinically relevant stem cell preparations.
With the exception of Bsik, there are presently no mechanisms to fund the innovative fundamental research of a consortium of expert developmental/molecular/stem cell scientists in different sites within the Netherlands. In addition to the Hubrecht Laboratory, there is clear developmental, molecular and stem cell expertise located in a number of research centers in the Netherlands (Rotterdam, Leiden and Amsterdam) as is demonstrated in the makeup of the consortium. The cooperation and integrated research of the consortium scientists will lead to added-value of the research already established in these centers. Bsik offers a timely and advantageous opportunity to bring all the experts together in an integrated and innovative plan to increase the knowledge base of Developmental and Stem Cell Biology and to support the important links with biomedical technology industries, such as Minos and Embyonic Stem Cells International, concerning the future of cell-based therapeutic strategies in health and medicine.
There is no question that the new frontier in stem cell based therapies for disease and trauma is through a better understanding of developmental processes. These developmental processes will be revealed through studies of the complex signaling and molecular regulatory pathways that provide individual cells with their identities. This consortium is based on this premise and uses a forward genetic approach. It is interesting to note that our consortium does not extend into the speciality of Tissue Engineering which includes the development of matrices/scaffolds, the study of matrice/scaffold interactions with cells and their surrounding tissues and the standardization of criteria for a successful repair/replacement of tissues and organs. However, the success of Tissues Engineering biomimetic and biomaterials technologies will rely on a comprehensive understanding of the temporal and spatial events taking place in normal embryonic development and disease, particularly the molecular regulation of cell fate determination. Hence, our Stem Cells, Development and Disease studies should form an important knowledge source for the future of the Tissue Engineering. Indeed, as a beginning to enter into the establishment of stem cells in engineered matrices, two consortium members (Mummery and Dzierzak) are involved in a Tissue Engineering application to Bsik.
The knowledge project on Stem Cells in Development and Disease will make fundamental contributions to our knowledge concerning developmental signaling processes that are used throughout life and deregulated in disease and trauma. The first and most obvious contribution is to the educational of a new generation of fundamental medical researchers. In this program we will train 8 Bsik funded postdoctoral fellows and 5 Bsik funded Ph.D. students (together with matching postdocs and students) in the latest theory, techniques and strategies in stem cell, developmental and molecular biology. They will guide the next innovations in biomedical technology and health research. The measureable scientific results of this program will be apparent in new strategies for future therapies in multifactorial disease and cell replacement and will involve molecules and cells for medical intervention. Furthermore, new biomedical research technologies and bioinformatic resources will be gained and will stimulate the participating biotechnology industries participating in this proposal to market diagnostic reagents, clinical grade cell prepartions, and other research reagents. More specific measureable results include:
- identifying functional gene networks and epigenetic controls governing cell fate decisions
- identifying possible targets (molecular or cellular) for future therapeutic intervention strategies
- providing diagnostic tools for purification/quality control of therapeutically relevant cells
Steps needed to embed results in the knowledge infrastructure are part of the scientific process and include the publication of results, communicating results at international/national conferences and educating young researchers as well as the general public. Rather than wait until the completion of the project, it is expected that as we reach set milestones, we will publish our results and communicate them to the biomedical community. We will also educate young researchers and the public. We are already very active in this area by organising a very popular course on genetics for non-geneticists as part of the research school MGC and giving many public lectures such as the "Laurens lezingen" in Rotterdam. In this way, the knowledge infrastructure grows more rapidly, will result in further integration and synergy and keep the public informed of progress. Concerning the marketing of biotechnologies and clinical intervention approaches, it is our intention together with our academic institutions and with our present industrial partner and industrial collaborators to protect intellectual property and bring applications to the market as soon as possible, whether during the frame of the knowledge project or thereafter. As other novel applications arise, we will approach these and other relevant industries for marketing.
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