Assessing risk and progression of pre-diabetes and type 2 diabetes to enable disease modification

The stated goal of RHAPSODY is to define a molecular taxonomy of type 2 diabetes mellitus (T2D) that will support patient segmentation, inform clinical trial design, and the establishment of regulatory paths for the adoption of novel strategies for diabetes prevention and treatment.

Our plans are built upon:
  • access to large European cohorts with comprehensive genetic analyses, rich longitudinal clinical, biochemical data and samples
  • detailed multi-omic maps of key T2D-relevant tissues and organs
  • large expertise in the development and use of novel genetic, epigenetic, biochemical and physiological experimental approaches
  • the ability to combine existing and novel data sets through effective data federation and use of these datasets in systems biology approaches towards precision medicine;
  • expertise in regulatory approval, health economics and patient engagement.

These activities will lead to the discovery of novel biomarkers for improved T2D taxonomy, to support development of pharmaceutical activities, and for use in precision medicine to improve health in Europe and worldwide.

Most recent publications

1.
Synthesis and in vivo behaviour of an exendin-4-based MRI probe capable of β-cell-dependent contrast enhancement in the pancreas.
Dalton Transactions 49, 4732-4740 (2020). doi:10.1039/D0DT00332H
2.
The type 2 diabetes gene product STARD10 is a phosphoinositide binding protein that controls insulin secretory granule biogenesis.
bioRxiv 2020.03.25.007286 (2020). doi:10.1101/2020.03.25.007286
3.
The influence of peptide context on signalling and trafficking of glucagon-like peptide-1 receptor biased agonists.
bioRxiv 2020.02.24.961524 (2020). doi:10.1101/2020.02.24.961524
4.
Effects of pharmacological modulators of α-synuclein and tau aggregation and internalization.
bioRxiv 2020.01.27.921643 (2020). doi:10.1101/2020.01.27.921643
5.
Klf6 protects β-cells against insulin resistance-induced dedifferentiation.
Molecular Metabolism (2020). doi:10.1016/j.molmet.2020.02.001
6.
Stearoyl CoA desaturase is a gatekeeper that protects human beta cells against lipotoxicity and maintains their identity.
Diabetologia 63, 395-409 (2020). doi:10.1007/s00125-019-05046-x
7.
The supply chain of human pancreatic β cell lines.
The Journal of Clinical Investigation 129, 3511-3520 (2019). doi:10.1172/JCI129484
8.
Use of preclinical models to identify markers of type 2 diabetes susceptibility and novel regulators of insulin secretion – A step towards precision medicine.
Molecular Metabolism 27, S147-S154 (2019). doi:10.1016/j.molmet.2019.06.008
9.
Fostering improved human islet research: a European perspective.
Diabetologia 62, 1514-1516 (2019). doi:10.1007/s00125-019-4911-4
10.
Leader β-cells coordinate Ca 2+ dynamics across pancreatic islets in vivo.
Nature Metabolism 1, 615 (2019). doi:10.1038/s42255-019-0075-2
11.
Laser capture microdissection of human pancreatic islets reveals novel eQTLs associated with type 2 diabetes.
Molecular Metabolism (2019). doi:10.1016/j.molmet.2019.03.004
12.
ICA512 RESP18 homology domain is a protein condensing factor and insulin fibrillation inhibitor.
bioRxiv 521351 (2019). doi:10.1101/521351
13.
The Expression of Aldolase B in Islets Is Negatively Associated With Insulin Secretion in Humans.
The Journal of Clinical Endocrinology & Metabolism 103, 4373-4383 (2018). doi:10.1210/jc.2018-00791
14.
Inflammatory stress in islet β-cells: therapeutic implications for type 2 diabetes?.
Current Opinion in Pharmacology 43, 40-45 (2018). doi:10.1016/j.coph.2018.08.002
15.
Pancreatic β-cell tRNA hypomethylation and fragmentation link TRMT10A deficiency with diabetes.
Nucleic Acids Research 46, 10302-10318 (2018). doi:10.1093/nar/gky839
16.
Prediction of Glucose Tolerance without an Oral Glucose Tolerance Test.
Frontiers in Endocrinology 9, (2018). doi:10.3389/fendo.2018.00082
17.
Novel subgroups of adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables.
The Lancet Diabetes & Endocrinology 6, 361-369 (2018). doi:10.1016/S2213-8587(18)30051-2
18.
Modeling human pancreatic beta cell dedifferentiation.
Molecular Metabolism 10, 74-86 (2018). doi:10.1016/j.molmet.2018.02.002
19.
MondoA Is an Essential Glucose-Responsive Transcription Factor in Human Pancreatic β-Cells.
Diabetes 67, 461-472 (2018). doi:10.2337/db17-0595
20.
HbA1c is associated with altered expression in blood of cell cycle- and immune response-related genes.
Diabetologia 61, 138-146 (2018). doi:10.1007/s00125-017-4467-0
21.
Endoplasmic reticulum stress and eIF2α phosphorylation: The Achilles heel of pancreatic β cells.
Molecular Metabolism 6, 1024-1039 (2017). doi:10.1016/j.molmet.2017.06.001
22.
Local and regional control of calcium dynamics in the pancreatic islet.
Diabetes, Obesity and Metabolism 19, 30-41 (2017). doi:10.1111/dom.12990
23.
NACHO: an R package for quality control of NanoString nCounter data.
Bioinformatics doi:10.1093/bioinformatics/btz647
24.
The tRNA epitranscriptome and diabetes: emergence of tRNA hypomodifications as a cause of pancreatic β-cell failure.
Endocrinology doi:10.1210/en.2019-00098
25.
Decision models of prediabetes populations: A systematic review.
Diabetes, Obesity and Metabolism doi:10.1111/dom.13684

1.
Synthesis and in vivo behaviour of an exendin-4-based MRI probe capable of β-cell-dependent contrast enhancement in the pancreas.
Dalton Transactions 49, 4732-4740 (2020). doi:10.1039/D0DT00332H
2.
The type 2 diabetes gene product STARD10 is a phosphoinositide binding protein that controls insulin secretory granule biogenesis.
bioRxiv 2020.03.25.007286 (2020). doi:10.1101/2020.03.25.007286
3.
The influence of peptide context on signalling and trafficking of glucagon-like peptide-1 receptor biased agonists.
bioRxiv 2020.02.24.961524 (2020). doi:10.1101/2020.02.24.961524
4.
Effects of pharmacological modulators of α-synuclein and tau aggregation and internalization.
bioRxiv 2020.01.27.921643 (2020). doi:10.1101/2020.01.27.921643
5.
Klf6 protects β-cells against insulin resistance-induced dedifferentiation.
Molecular Metabolism (2020). doi:10.1016/j.molmet.2020.02.001
6.
Stearoyl CoA desaturase is a gatekeeper that protects human beta cells against lipotoxicity and maintains their identity.
Diabetologia 63, 395-409 (2020). doi:10.1007/s00125-019-05046-x
7.
The supply chain of human pancreatic β cell lines.
The Journal of Clinical Investigation 129, 3511-3520 (2019). doi:10.1172/JCI129484
8.
Use of preclinical models to identify markers of type 2 diabetes susceptibility and novel regulators of insulin secretion – A step towards precision medicine.
Molecular Metabolism 27, S147-S154 (2019). doi:10.1016/j.molmet.2019.06.008
9.
Fostering improved human islet research: a European perspective.
Diabetologia 62, 1514-1516 (2019). doi:10.1007/s00125-019-4911-4
10.
Leader β-cells coordinate Ca 2+ dynamics across pancreatic islets in vivo.
Nature Metabolism 1, 615 (2019). doi:10.1038/s42255-019-0075-2
11.
Laser capture microdissection of human pancreatic islets reveals novel eQTLs associated with type 2 diabetes.
Molecular Metabolism (2019). doi:10.1016/j.molmet.2019.03.004
12.
ICA512 RESP18 homology domain is a protein condensing factor and insulin fibrillation inhibitor.
bioRxiv 521351 (2019). doi:10.1101/521351
13.
The Expression of Aldolase B in Islets Is Negatively Associated With Insulin Secretion in Humans.
The Journal of Clinical Endocrinology & Metabolism 103, 4373-4383 (2018). doi:10.1210/jc.2018-00791
14.
Inflammatory stress in islet β-cells: therapeutic implications for type 2 diabetes?.
Current Opinion in Pharmacology 43, 40-45 (2018). doi:10.1016/j.coph.2018.08.002
15.
Pancreatic β-cell tRNA hypomethylation and fragmentation link TRMT10A deficiency with diabetes.
Nucleic Acids Research 46, 10302-10318 (2018). doi:10.1093/nar/gky839
16.
Prediction of Glucose Tolerance without an Oral Glucose Tolerance Test.
Frontiers in Endocrinology 9, (2018). doi:10.3389/fendo.2018.00082
17.
Novel subgroups of adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables.
The Lancet Diabetes & Endocrinology 6, 361-369 (2018). doi:10.1016/S2213-8587(18)30051-2
18.
Modeling human pancreatic beta cell dedifferentiation.
Molecular Metabolism 10, 74-86 (2018). doi:10.1016/j.molmet.2018.02.002
19.
MondoA Is an Essential Glucose-Responsive Transcription Factor in Human Pancreatic β-Cells.
Diabetes 67, 461-472 (2018). doi:10.2337/db17-0595
20.
HbA1c is associated with altered expression in blood of cell cycle- and immune response-related genes.
Diabetologia 61, 138-146 (2018). doi:10.1007/s00125-017-4467-0
21.
Endoplasmic reticulum stress and eIF2α phosphorylation: The Achilles heel of pancreatic β cells.
Molecular Metabolism 6, 1024-1039 (2017). doi:10.1016/j.molmet.2017.06.001
22.
Local and regional control of calcium dynamics in the pancreatic islet.
Diabetes, Obesity and Metabolism 19, 30-41 (2017). doi:10.1111/dom.12990
23.
NACHO: an R package for quality control of NanoString nCounter data.
Bioinformatics doi:10.1093/bioinformatics/btz647
24.
The tRNA epitranscriptome and diabetes: emergence of tRNA hypomodifications as a cause of pancreatic β-cell failure.
Endocrinology doi:10.1210/en.2019-00098
25.
Decision models of prediabetes populations: A systematic review.
Diabetes, Obesity and Metabolism doi:10.1111/dom.13684

1.
Synthesis and in vivo behaviour of an exendin-4-based MRI probe capable of β-cell-dependent contrast enhancement in the pancreas.
Dalton Transactions 49, 4732-4740 (2020). doi:10.1039/D0DT00332H
2.
The type 2 diabetes gene product STARD10 is a phosphoinositide binding protein that controls insulin secretory granule biogenesis.
bioRxiv 2020.03.25.007286 (2020). doi:10.1101/2020.03.25.007286
3.
The influence of peptide context on signalling and trafficking of glucagon-like peptide-1 receptor biased agonists.
bioRxiv 2020.02.24.961524 (2020). doi:10.1101/2020.02.24.961524
4.
Effects of pharmacological modulators of α-synuclein and tau aggregation and internalization.
bioRxiv 2020.01.27.921643 (2020). doi:10.1101/2020.01.27.921643
5.
Klf6 protects β-cells against insulin resistance-induced dedifferentiation.
Molecular Metabolism (2020). doi:10.1016/j.molmet.2020.02.001
6.
Stearoyl CoA desaturase is a gatekeeper that protects human beta cells against lipotoxicity and maintains their identity.
Diabetologia 63, 395-409 (2020). doi:10.1007/s00125-019-05046-x
7.
The supply chain of human pancreatic β cell lines.
The Journal of Clinical Investigation 129, 3511-3520 (2019). doi:10.1172/JCI129484
8.
Use of preclinical models to identify markers of type 2 diabetes susceptibility and novel regulators of insulin secretion – A step towards precision medicine.
Molecular Metabolism 27, S147-S154 (2019). doi:10.1016/j.molmet.2019.06.008
9.
Fostering improved human islet research: a European perspective.
Diabetologia 62, 1514-1516 (2019). doi:10.1007/s00125-019-4911-4
10.
Leader β-cells coordinate Ca 2+ dynamics across pancreatic islets in vivo.
Nature Metabolism 1, 615 (2019). doi:10.1038/s42255-019-0075-2
11.
Laser capture microdissection of human pancreatic islets reveals novel eQTLs associated with type 2 diabetes.
Molecular Metabolism (2019). doi:10.1016/j.molmet.2019.03.004
12.
ICA512 RESP18 homology domain is a protein condensing factor and insulin fibrillation inhibitor.
bioRxiv 521351 (2019). doi:10.1101/521351
13.
The Expression of Aldolase B in Islets Is Negatively Associated With Insulin Secretion in Humans.
The Journal of Clinical Endocrinology & Metabolism 103, 4373-4383 (2018). doi:10.1210/jc.2018-00791
14.
Inflammatory stress in islet β-cells: therapeutic implications for type 2 diabetes?.
Current Opinion in Pharmacology 43, 40-45 (2018). doi:10.1016/j.coph.2018.08.002
15.
Pancreatic β-cell tRNA hypomethylation and fragmentation link TRMT10A deficiency with diabetes.
Nucleic Acids Research 46, 10302-10318 (2018). doi:10.1093/nar/gky839
16.
Prediction of Glucose Tolerance without an Oral Glucose Tolerance Test.
Frontiers in Endocrinology 9, (2018). doi:10.3389/fendo.2018.00082
17.
Novel subgroups of adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables.
The Lancet Diabetes & Endocrinology 6, 361-369 (2018). doi:10.1016/S2213-8587(18)30051-2
18.
Modeling human pancreatic beta cell dedifferentiation.
Molecular Metabolism 10, 74-86 (2018). doi:10.1016/j.molmet.2018.02.002
19.
MondoA Is an Essential Glucose-Responsive Transcription Factor in Human Pancreatic β-Cells.
Diabetes 67, 461-472 (2018). doi:10.2337/db17-0595
20.
HbA1c is associated with altered expression in blood of cell cycle- and immune response-related genes.
Diabetologia 61, 138-146 (2018). doi:10.1007/s00125-017-4467-0
21.
Endoplasmic reticulum stress and eIF2α phosphorylation: The Achilles heel of pancreatic β cells.
Molecular Metabolism 6, 1024-1039 (2017). doi:10.1016/j.molmet.2017.06.001
22.
Local and regional control of calcium dynamics in the pancreatic islet.
Diabetes, Obesity and Metabolism 19, 30-41 (2017). doi:10.1111/dom.12990
23.
NACHO: an R package for quality control of NanoString nCounter data.
Bioinformatics doi:10.1093/bioinformatics/btz647
24.
The tRNA epitranscriptome and diabetes: emergence of tRNA hypomodifications as a cause of pancreatic β-cell failure.
Endocrinology doi:10.1210/en.2019-00098
25.
Decision models of prediabetes populations: A systematic review.
Diabetes, Obesity and Metabolism doi:10.1111/dom.13684

1.
Synthesis and in vivo behaviour of an exendin-4-based MRI probe capable of β-cell-dependent contrast enhancement in the pancreas.
Dalton Transactions 49, 4732-4740 (2020). doi:10.1039/D0DT00332H
2.
The type 2 diabetes gene product STARD10 is a phosphoinositide binding protein that controls insulin secretory granule biogenesis.
bioRxiv 2020.03.25.007286 (2020). doi:10.1101/2020.03.25.007286
3.
The influence of peptide context on signalling and trafficking of glucagon-like peptide-1 receptor biased agonists.
bioRxiv 2020.02.24.961524 (2020). doi:10.1101/2020.02.24.961524
4.
Effects of pharmacological modulators of α-synuclein and tau aggregation and internalization.
bioRxiv 2020.01.27.921643 (2020). doi:10.1101/2020.01.27.921643
5.
Klf6 protects β-cells against insulin resistance-induced dedifferentiation.
Molecular Metabolism (2020). doi:10.1016/j.molmet.2020.02.001
6.
Stearoyl CoA desaturase is a gatekeeper that protects human beta cells against lipotoxicity and maintains their identity.
Diabetologia 63, 395-409 (2020). doi:10.1007/s00125-019-05046-x
7.
The supply chain of human pancreatic β cell lines.
The Journal of Clinical Investigation 129, 3511-3520 (2019). doi:10.1172/JCI129484
8.
Use of preclinical models to identify markers of type 2 diabetes susceptibility and novel regulators of insulin secretion – A step towards precision medicine.
Molecular Metabolism 27, S147-S154 (2019). doi:10.1016/j.molmet.2019.06.008
9.
Fostering improved human islet research: a European perspective.
Diabetologia 62, 1514-1516 (2019). doi:10.1007/s00125-019-4911-4
10.
Leader β-cells coordinate Ca 2+ dynamics across pancreatic islets in vivo.
Nature Metabolism 1, 615 (2019). doi:10.1038/s42255-019-0075-2
11.
Laser capture microdissection of human pancreatic islets reveals novel eQTLs associated with type 2 diabetes.
Molecular Metabolism (2019). doi:10.1016/j.molmet.2019.03.004
12.
ICA512 RESP18 homology domain is a protein condensing factor and insulin fibrillation inhibitor.
bioRxiv 521351 (2019). doi:10.1101/521351
13.
The Expression of Aldolase B in Islets Is Negatively Associated With Insulin Secretion in Humans.
The Journal of Clinical Endocrinology & Metabolism 103, 4373-4383 (2018). doi:10.1210/jc.2018-00791
14.
Inflammatory stress in islet β-cells: therapeutic implications for type 2 diabetes?.
Current Opinion in Pharmacology 43, 40-45 (2018). doi:10.1016/j.coph.2018.08.002
15.
Pancreatic β-cell tRNA hypomethylation and fragmentation link TRMT10A deficiency with diabetes.
Nucleic Acids Research 46, 10302-10318 (2018). doi:10.1093/nar/gky839
16.
Prediction of Glucose Tolerance without an Oral Glucose Tolerance Test.
Frontiers in Endocrinology 9, (2018). doi:10.3389/fendo.2018.00082
17.
Novel subgroups of adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables.
The Lancet Diabetes & Endocrinology 6, 361-369 (2018). doi:10.1016/S2213-8587(18)30051-2
18.
Modeling human pancreatic beta cell dedifferentiation.
Molecular Metabolism 10, 74-86 (2018). doi:10.1016/j.molmet.2018.02.002
19.
MondoA Is an Essential Glucose-Responsive Transcription Factor in Human Pancreatic β-Cells.
Diabetes 67, 461-472 (2018). doi:10.2337/db17-0595
20.
HbA1c is associated with altered expression in blood of cell cycle- and immune response-related genes.
Diabetologia 61, 138-146 (2018). doi:10.1007/s00125-017-4467-0
21.
Endoplasmic reticulum stress and eIF2α phosphorylation: The Achilles heel of pancreatic β cells.
Molecular Metabolism 6, 1024-1039 (2017). doi:10.1016/j.molmet.2017.06.001
22.
Local and regional control of calcium dynamics in the pancreatic islet.
Diabetes, Obesity and Metabolism 19, 30-41 (2017). doi:10.1111/dom.12990
23.
NACHO: an R package for quality control of NanoString nCounter data.
Bioinformatics doi:10.1093/bioinformatics/btz647
24.
The tRNA epitranscriptome and diabetes: emergence of tRNA hypomodifications as a cause of pancreatic β-cell failure.
Endocrinology doi:10.1210/en.2019-00098
25.
Decision models of prediabetes populations: A systematic review.
Diabetes, Obesity and Metabolism doi:10.1111/dom.13684

1.
Synthesis and in vivo behaviour of an exendin-4-based MRI probe capable of β-cell-dependent contrast enhancement in the pancreas.
Dalton Transactions 49, 4732-4740 (2020). doi:10.1039/D0DT00332H
2.
The type 2 diabetes gene product STARD10 is a phosphoinositide binding protein that controls insulin secretory granule biogenesis.
bioRxiv 2020.03.25.007286 (2020). doi:10.1101/2020.03.25.007286
3.
The influence of peptide context on signalling and trafficking of glucagon-like peptide-1 receptor biased agonists.
bioRxiv 2020.02.24.961524 (2020). doi:10.1101/2020.02.24.961524
4.
Effects of pharmacological modulators of α-synuclein and tau aggregation and internalization.
bioRxiv 2020.01.27.921643 (2020). doi:10.1101/2020.01.27.921643
5.
Klf6 protects β-cells against insulin resistance-induced dedifferentiation.
Molecular Metabolism (2020). doi:10.1016/j.molmet.2020.02.001
6.
Stearoyl CoA desaturase is a gatekeeper that protects human beta cells against lipotoxicity and maintains their identity.
Diabetologia 63, 395-409 (2020). doi:10.1007/s00125-019-05046-x
7.
The supply chain of human pancreatic β cell lines.
The Journal of Clinical Investigation 129, 3511-3520 (2019). doi:10.1172/JCI129484
8.
Use of preclinical models to identify markers of type 2 diabetes susceptibility and novel regulators of insulin secretion – A step towards precision medicine.
Molecular Metabolism 27, S147-S154 (2019). doi:10.1016/j.molmet.2019.06.008
9.
Fostering improved human islet research: a European perspective.
Diabetologia 62, 1514-1516 (2019). doi:10.1007/s00125-019-4911-4
10.
Leader β-cells coordinate Ca 2+ dynamics across pancreatic islets in vivo.
Nature Metabolism 1, 615 (2019). doi:10.1038/s42255-019-0075-2
11.
Laser capture microdissection of human pancreatic islets reveals novel eQTLs associated with type 2 diabetes.
Molecular Metabolism (2019). doi:10.1016/j.molmet.2019.03.004
12.
ICA512 RESP18 homology domain is a protein condensing factor and insulin fibrillation inhibitor.
bioRxiv 521351 (2019). doi:10.1101/521351
13.
The Expression of Aldolase B in Islets Is Negatively Associated With Insulin Secretion in Humans.
The Journal of Clinical Endocrinology & Metabolism 103, 4373-4383 (2018). doi:10.1210/jc.2018-00791
14.
Inflammatory stress in islet β-cells: therapeutic implications for type 2 diabetes?.
Current Opinion in Pharmacology 43, 40-45 (2018). doi:10.1016/j.coph.2018.08.002
15.
Pancreatic β-cell tRNA hypomethylation and fragmentation link TRMT10A deficiency with diabetes.
Nucleic Acids Research 46, 10302-10318 (2018). doi:10.1093/nar/gky839
16.
Prediction of Glucose Tolerance without an Oral Glucose Tolerance Test.
Frontiers in Endocrinology 9, (2018). doi:10.3389/fendo.2018.00082
17.
Novel subgroups of adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables.
The Lancet Diabetes & Endocrinology 6, 361-369 (2018). doi:10.1016/S2213-8587(18)30051-2
18.
Modeling human pancreatic beta cell dedifferentiation.
Molecular Metabolism 10, 74-86 (2018). doi:10.1016/j.molmet.2018.02.002
19.
MondoA Is an Essential Glucose-Responsive Transcription Factor in Human Pancreatic β-Cells.
Diabetes 67, 461-472 (2018). doi:10.2337/db17-0595
20.
HbA1c is associated with altered expression in blood of cell cycle- and immune response-related genes.
Diabetologia 61, 138-146 (2018). doi:10.1007/s00125-017-4467-0
21.
Endoplasmic reticulum stress and eIF2α phosphorylation: The Achilles heel of pancreatic β cells.
Molecular Metabolism 6, 1024-1039 (2017). doi:10.1016/j.molmet.2017.06.001
22.
Local and regional control of calcium dynamics in the pancreatic islet.
Diabetes, Obesity and Metabolism 19, 30-41 (2017). doi:10.1111/dom.12990
23.
NACHO: an R package for quality control of NanoString nCounter data.
Bioinformatics doi:10.1093/bioinformatics/btz647
24.
The tRNA epitranscriptome and diabetes: emergence of tRNA hypomodifications as a cause of pancreatic β-cell failure.
Endocrinology doi:10.1210/en.2019-00098
25.
Decision models of prediabetes populations: A systematic review.
Diabetes, Obesity and Metabolism doi:10.1111/dom.13684


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This project receives funding from the Innovative Medicines Initiative 2 Joint Undertaking (www.imi.europa.eu) under grant agreement No 115881. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA.

This work is supported by the Swiss State Secretariat for Education‚ Research and Innovation (SERI) under contract number 16.0097-2.

The opinions expressed and arguments employed herein do not necessarily reflect the official views of these funding bodies.