Proteomics profiling of RNAi in human cells

Cenix BioScience (Dresden), Applied Biosystems, and the Biotechnology Centre (Biotec) of the Technische Universitat Dresden (TUD) have announced a collaboration to establish a new joint facility to pioneer the convergence of two of the most powerful research methodologies driving pharmaceutical drug discovery today: functional genomics and proteomics.

The new facility will enable scientists from the three organisations to develop and deliver novel research tools and methodologies that enable more detailed and probative analyses of the cellular functions of therapeutically-relevant genes.

As such, this work promises to improve the predictive value of early pre-clinical drug development, ultimately reducing the risks of unwanted side effects from future medicines.

A German federal grant of euro1.2million has been issued to support the efforts of this two-year project through the BioChance Plus grant programme.

The three partners bring complementary core competencies to the project.

Cenix BioScience is a specialist in advanced, cell-based applications of RNA interference (RNAi), a breakthrough gene silencing technology for the discovery and functional characterisation of novel therapeutic target genes and drug candidates.

Applied Biosystems contributes integrated genetic and proteomic systems technology as well as RNAi reagents.

The Biotec centre of the Technische Universitat Dresden combines dynamic academic training programmes with interdisciplinary research in biotechnology.

The two-year project will stretch the limits of today's most advanced technologies for analyzing gene function and drug action through cellular phenotyping, ie, the detection and measurement of changes in the behavior of living cells after the application of pharmaceutical agents or other treatments that modulate gene expression.

Among the latter, RNAi-based gene knock-down has recently emerged as the most powerful functional genomic method for harnessing the full power of the completed Human Genome Project, using genome sequences to drive assays of gene function and for predicting the effects of future inhibitory drugs.

Until now, the broadest, highest content phenotyping approaches could only probe the so-called transcriptome level of gene expression, whereby cDNA microarrays have enabled measurements of thousands of gene transcripts simultaneously.

However, in order to truly understand the full complexity of gene function, phenotypes must be examined at the level of the final, functional gene product: the protein.

Despite the success of high content microscopy-based assays, broad proteome-level profiling has remained much less developed, primarily due to inherent limitations of antibody-based approaches.

The present project will seek to overcome these limitations by developing broad, quantitative surveys of protein levels in RNAi- and drug-treated cells using antibody-independent, mass spectrometry-based analyses.

This initiative represents a new effort by Cenix in its continuing mission to strengthen and broaden the discovery potential of RNAi-based experimentation through high-resolution phenotypic analyses.

Cenix will integrate the newly developed capabilities within its leading range of advanced RNAi-based research service programs for target discovery, target validation and drug mode of action analyses.

"This is the natural next step in high content analysis not only for RNAi experiments, but also for studying therapeutic drug effects and a wide variety of other experimental strategies common to both basic and applied research", notes Christophe Echeverri, CEO/CSO of Cenix.

Technologies for the collaboration from Applied Biosystems will include mass spectrometry systems, iTraq protein labelling reagents, customised TaqMan gene expression assays, and its Ambion range of RNAi knock-down reagents.

Applied Biosystems's contributions to the project will be coordinated from its Science Centre Europe, located in Darmstadt, Germany.

"Applied Biosystems has a 25-year history of collaborating with leading researchers in academia and industry on a global basis," said Lars Holmkvist, Applied Biosystems president for Europe.

"We are confident that this collaboration in Europe will enable significant innovative advances in cell biology and for marker discovery and validation in the pharmaceutical industry".

This collaboration is a further manifestation of the strong industry-academic cooperation being fostered within Dresden's growing life science research community.

The new facility will be located within the Dresden Bio-Innovation Centre, adding further strength to the existing Biotec research group for Proteomics now led by Bernard Hoflack.

Prof Hoflack joined the Biotec/TUD in 2003 after holding previous positions at Washington University (St Louis, USA), the European Molecular Biology Laboratory (Heidelberg, Germany) and the Pasteur Institute (Lille, France).

"We are proud to demonstrate again the pivotal role of the Biotec for connecting scientific, social and economic interests in the Dresden life science research community," said Hoflack.

"As a researcher focused on bone biology and osteoporosis, I welcome this cooperation with industrial partners to help accelerate and enhance our basic research efforts, facilitating their translation towards future therapeutic applications."