What is the problem to be addressed
CELL-O-MATIC will address the problem of how to access genome information at a resolution and with a fidelity that enable mechanistic insights and is instructive for healthcare. Advances in genome sequencing technologies now enable
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individual genomes to be sequenced at relatively low cost ($5-10000 per genome)
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sequence comparison of normal and cancer cells in single individuals, which has revealed somatic mutations that are present in the tumour only.
The broad sweep of ensemble cell-analysis masks inter-cell heterogeneity, which modern biology and medicine have neglected until very recently.
It is clear that there is substantial genomic diversity in the cells comprising a tumour; some of these cells may be metastatic and others may be capable of initiating tumours. Without the elimination of the latter cells, a tumour in remission may regress.
Sequencing has now become sufficiently cheap and high-throughput to contemplate
The problem is that it is neither easy, cheap nor currently effective to analyze a population of cells individually. There are a number of bottlenecks in sequencing technology today:
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high-throughput sequencing requires several days and hundreds of Euros devoted to upfront sample preparation which is further increased when sequencing selected parts of the genome;
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genome assembly relies on computationally intensive comparisons to the reference genome because existing technologies produce short sequence reads;
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it is currently challenging to work with small amounts of sample material comprising micro-biopsies and single-cells;
Results to date show very low genome sequence coverage and the whole genome amplification that is required before high-throughput sequencing leads to contaminants that obscure the genomic sequences from the single-cell.
What is the proposed solution
The proposed solution is to develop lab-on-a-chip technology that provides the sensitivity required to analyse single cells, provides high genome coverage and is not susceptible to promiscuous amplification. The approach should be applicable in the various settings where single-cell analysis is important and should be streamlined, automatable, high-throughput and low cost.
What radical innovations are expected
The radical innovations that can be expected are new capabilities in micro and nanofluidics, new low cost/ mass production chips, contamination free/ full coverage genome sequencing from single-cells, ability to select megabase regions in which haplotypes are resolved. In addition if the programme is successful it will lead to clinical decision-making based on comprehensive information that is personalized to an individual’s tumour and is predictive of progression and response to treatment.
Why is this the ideal consortium for the project and what are the major benefits for the SMEs
CELL-O-MATIC is a highly interdisciplinary project and consortium with a strong management structure. The consortium is ideal because it contains the diverse range of expertises that is needed to bring about a much-needed change in biomedical science: From analysing cells and molecules in bulk, which shows their average characteristics and behaviour, to single-cell and single-molecule analyse that unmasks cell-to-cell and molecule-to-molecule variability.
The consortium is ideal because it fosters research and development activities in SME partners. The SME partners are likely to benefit strongly from their collaboration with leading academic researchers and highly successful multi-national companies and from gaining access to highly innovative bleeding-edge technologies. This will increase the market competitiveness of the SMEs and their collaboration with the two participating European multi-nationals, ROCHE and PHILIPS, will increase the competitiveness of European companies.