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  3. Elucidate the role of sFRP2 in lung or skin fibrosis

Elucidate the role of sFRP2 in lung or skin fibrosis

How would you propose to elucidate and validate the role of secreted Frizzled related protein 2 (sFRP2) in the context of lung or skin fibrosis whereby sFRP2 may either lead to disease progression or inhibition of resolution?

Franziska Elena Herrmann

Franziska Elena Herrmann 
Principal Scientist 
Boehringer Ingelheim

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Call for proposals: All incoming answers accompanied by a collaboration proposal will be evaluated by a scientific jury, and, upon selection, chosen proposals are pursued through a joint collaboration with the successful applicants. Initial funding of up to 200,000 euros will be available for each selected proposal.

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Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung disease of unknown cause, with high mortality. Currently, there are two approved antifibrotic drugs that slow, but do not stop the progression of fibrosis. Therefore, additional treatments are needed to inhibit or even revert the disease.

Secreted Frizzled related protein 2 (sFRP2) is a protein that has been implicated in the WNT signaling pathway, which plays a role in tissue development and repair. Furthermore, sFRP2 was described to have a role in cardiac fibrosis and tumor progression. An increased expression of sFRP2 was also found in myofibroblasts from systemic sclerosis (SSc) patients. However, the contribution to lung or skin fibrosis progression or resolution remains unclear. Offered pathways, all known to be involved in fibrotic conditions, such as WNT-FRZD receptor interaction, BMP1 interaction, or interference with SMAD signaling were proposed previously, however it is unclear if the binding to those proteins leads to disease progression, or if progression is caused by yet unknown mechanisms or interaction partners. Although the name sFRP2 suggests a relation to WNT, beta-catenin, and Frizzled signaling, we do not necessarily think the solution is (solely) in the WNT space.

As part of our current opnMe call, we look forward to receiving creative ideas to decipher the contribution of sFRP2 in lung or skin fibrosis. Furthermore, we aim to elucidate the mode of action/ binding partner that leads to the pathologic phenotype, in best case including proximity markers. The ideal solution should deliver a potential starting point for novel therapeutic interventions against sFRP2 in lung or skin fibrosis.

  • Any unconventional, but feasible scientific idea that provides a link between sFRP2 and lung or skin fibrosis progression or influence of resolution using cellular systems and/or in vivo models
  • Any unconventional, but feasible scientific idea that allows identifying and validating (novel) sFRP2 interacting partner(s), responsible for the pathologic phenotype, in the context of lung or skin fibrosis
  • Identification and validation of proximity marker(s): Pathway or players that provide a mechanistic link between sFRP2 and fibrosis
  • In our opinion, a thorough validation will include an in-depth analysis package consisting of biochemical, and biophysical analyses
  • Any unconventional but feasible approach should be based on existing assays and available tools in your laboratory
  • Initial data are a plus, but conceptually proposals might be acceptable
  • Purely computational approaches
  • Proposals without major focus on lung or skin fibrosis
  • Proposals focusing on mechanisms of action that are unique or specific to non-human species
  • Proposals for cell systems lacking applications to the disease setting
  • Purely descriptive binding partners, without linkage to pathology

If your project is selected, you will have the opportunity to directly collaborate with the Immunology and Respiratory Discovery Research team of Boehringer Ingelheim. As an incentive specific to this opn2EXPERTS call, we offer an exclusive access to non-commercial, quality reagents and tools to validate your submitted hypotheses, should your proposal be selected by our scientific review team. In addition, you can also expect appropriate funding for the prospective collaboration period. Your exact funding request should be outlined in your proposal. As a framework, we suggest that your initial funding request is structured in milestones and does not exceed 200,000 euros per submitted project in total (including direct, indirect, overhead costs).

Our collaboration agreement will provide full transparency about each partner’s rights & obligations (including intellectual property rights). As part of the agreement, you will be encouraged to publish following the collaboration agreement (to be negotiated in good faith).

To maintain the highest degree possible in an open innovation environment, we plan to announce the winner(s) publicly and feature them on opnMe.com and our social media channels.

We are seeking research collaboration proposals that contain:

  • A well-structured proposal outlining a new and compelling scientific approach including an experimental plan that will be used to test your hypothesis.
  • A novel, testable working hypothesis distinct from those previously published.
  • A thorough validation that includes an in-depth analysis package consisting of biochemical, and biophysical analyses.
  • Outlining of the technical feasibility, and potentially existing data or previous publications that support feasibility / experience with outlined technology, based on existing techniques and established assays.
  • Potentially includes (non-confidential) existing data and results. 
  • Your exact funding request should be outlined in your proposal based on a well-thought-through project. The project should be structured in milestones and planned with key decision points (clear Go/No-Go criteria). The funding request for the initial milestones resulting in a Go/No-Go decision should not exceed 200,000 euros per submitted project in total.
  • Proven track record in the required field of expertise.
  • Ability to implement the outlined solution as part of a scientific collaboration project with Boehringer Ingelheim including access to a laboratory.
  • Anything considerably longer than 2 years will be excluded

Please use our answer submission template to provide a 2-3 page non-confidential proposal (available for download here).

If confidential data exists that would strengthen the proposal, please indicate that information is available to share under a Confidential Disclosure Agreement (CDA). If we find the non-confidential concept proposal sufficiently interesting, we will execute a CDA for confidential discussions.

We are currently seeking answers for the following scientific challenge: How would you propose to elucidate and validate the role of sFRP2 in the context of lung or skin fibrosis whereby sFRP2 may either lead to disease progression or inhibition of resolution?

All incoming answers accompanied by a collaboration proposal will be evaluated by a scientific jury, and, upon selection, chosen proposals are pursued through a joint collaboration with the successful applicants. Initial funding of up to 200,000 euros will be available for each selected proposal.

We can only accept research proposals if they arrive by the submission deadline on July 11, 2023, 11.59 pm PST.

Multiple Roles of sFRP2 in Cardiac Development and Cardiovascular Disease

Wu Y., Liu X., Zheng H., Zhu H., Mai W., Huang X., Huang Y.

Int J Biol Sci 2020, 16(5):730-738.

DOI
PubMed

Secreted frizzled-related protein 2: a key player in noncanonical Wnt signaling and tumor angiogenesis

van Loon K., Huijbers E.J.M., Griffioen A.W.

Cancer Metastasis Rev 2021, 40, 191–203.

DOI
PubMed

Myofibroblast transcriptome indicates SFRP2hi fibroblast progenitors in systemic sclerosis skin

Tabib T., Huang M., Morse N., Papazoglou A., Behera R., Jia M., Bulik M., Monier D. E., Benos P. V., Chen W., Domsic R., Lafyatis R.

Nat Commun 2021, 12, 4384.

DOI
PubMed
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