Partners

Universitat Basel (2) represented by Prof. Wolfgang Holzgreve and Prof. Sinuhe Hanh
University of the West of England (3) represented by Prof. Neil Avent
Medizinische Universitat Graz (8a) represented by Prof. Barbara Pertl
University of Helsinki (13) represented by Prof. Jim Schroeder
University of Aberdeen (15) represented by Prof. Stan Urbaniak
University Medical Center Nijmegen represented (17) by Dr Dorine Swinkels
National and Kapodistrian University of Athens (19) represented by Dr Ariadni Mavrou
Cham Sheba Medical Center (21) represented by Dr Esther Guetta
Cyprus Institute of Neurology and Genetics (25a) represented by Dr Marina Kleanthous
University of Bristol (26a and 26b) represented by Prof Peter Soothill and Prof. Bernard Lopez
Universita Degli Studi di Perugia (28) represented by Prof. Gian Carlo di Renzo
Georg- August- Universiteat Goettingen (29) represented by Dr Tobias Legler
UCL (41a) University College London (41a and 41b) represented by Prof. Charles Rodeck and Dr Lun Chitty
INSERM 2 (43) represented by Prof. Jean-Jacques Toulme
Stetens Serum Intitut (52b) represented by Dr Paal Skytt Andersen

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Objectives

WP3B began its activity during the M25-42 period as a result of recommendations by the EC reviewers, largely because the programme of activities within the original workpackage 3 were too numerous to be managed within one entity. WP3B evolved to explore the massive potential of post-genomics technologies in NIPD. In particular it is focused toward the development of new protein-based assays which may be a cheap and more accurate alternative to the nucleic acid based approaches being explored in WP3A. In particular WP3B may provide a series of novel diagnostic strategies for key targets where NIPD would be most requested, namely in the analysis of aneuploidy.
WP3B has been segregated into two major sub-workpackages (A. Proteomics and B. Transcriptomics), both of which have identical goals. Gene expression in the placenta (and also within the developing fetus) offers a significant opportunity to study the release of biomarkers and associated metabolites into the maternal circulation. Each fetal anomaly may produce a "signature" of such biomarkers and metabolites and thus provide the opportunity for diagnosis of disease. As such, study of gene expression directly within placental tissue using transcriptomics based approaches maybe ultimately as productive as the investigation of low abundant protein species found in plasma. The latter studies employ plasma proteomics, which is a highly technically demanding discipline within proteomics as this is the most complex of the human proteomes. A variety of collaborative studies are ongoing including the depletion of the major protein species within plasma in order to increase the chance of the identification of low abundance species. Furthermore separation of proteins is being performed by free-flow electrophoresis and advanced two-dimensional gel electrophoresis.
Candidate biomarkers have been identified and those for aneuploidy, pre-term labour and preeclampsia will feature significantly in future investigations. They will also feature in the long-term objective of the introduction of a new generation of protein based diagnostic tests for complications of pregnancy. These biomarkers will be subjected to a rigorous analysis using the SAFE co-ordinated cohort of samples - the SAFE biobank. SAFE will, wherever possible, primarily exploit the identified biomarkers for the implementation of diagnostic assays for introduction as rapidly as possible into NIPD. However, we are also duty bound wherever possible to further explore the biology of disease in order to ameliorate or obviate the symptoms of disease in utero. In preeclampsia for example, the involvement of neutophils in the disease is poorly characterized and WP3B is exploring the production of Neutophil extracellular traps (NETS) in this disease.
WP3B has been a major exploiter of the New Technology Resource Centre (NTRC) which is organised by WP4. The NTRC has provided the consortium with an overview of the technology available within the consortium for highly technically demanding projects such as those hosted by WP3B. The technology includes microarray fabrication and processing facilities, proteomics instrumentation including two-dimensional gel electrophoresis, Difference in-Gel Electrophoresis (DiGE), and mass spectrometry.

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Description of work

3B1.1 Plasma Proteomics for markers of Aneuploidy
3B1.2 Proteomics of preeclampsia (PET) and Interuterine growth restriction (IUGR)
3B1.3 Proteomics of Preterm labour
3B1.4 Placental Proteomics
3B1.5 The presence of placental NETS (Neutrophil extracellular traps
3B2.1 Microarray analysis of Placental material
3B2.2 Free fetal mRNA: Analysis of free fetal RNA in Aneuploidy and preterm labour