Deciphering molecular targets of human Myeloid-Derived Growth Factor (MYDGF)

Human Myeloid-Derived Growth Factor (MYDGF) is a 142 amino acid-long protein with incompletely understood (patho)physiological functions. It was initially found to be secreted from bone marrow-derived monocytes and macrophages (1, 2). Subsequently, others described MYDGF to also be an endoplasmatic reticulum-resident protein, with broad expression across several tissues, fluids, and in various cell lines (3-5).

MYDGF has been implicated in cardiac repair after myocardial infarction by inhibiting ischemia-reperfusion-associated cardiomyocyte apoptosis and by promoting angiogenesis in the infarct border (1, 6). Further studies suggest diverse (patho)physiological functions that may be context-dependent. For instance, a role in glucose homeostasis has been postulated through MYDGF’s induction of glucagon-like peptide-1 (GLP-1) secretion from intestinal epithelial endocrine L-cells. MYDGF has additionally been identified in the secretome of cancer cell lines (7).

Although MYDGF’s structure and functionally important moieties have been defined (4, 8), the molecular mechanisms underpinning its biological effects need further elucidation. In the context of cardiac repair, MYDGF is thought to function as a secreted protein and to activate down-stream signaling pathways in target cells, i.e. cardiomyocytes and endothelial cells (1). The primary molecular MYDGF targets, however, are yet to be discovered. Identification of MYDGF interactors would improve our mechanistic understanding of MYDGF’s functional effects and would deliver valuable insights on the full therapeutic potential of this exciting protein. We invite you to propose unconventional strategies how to identify molecular MYDGF targets.

Any unconventional but feasible approach that allows identifying and verifying MYDGF interactors from biological matrices such as primary cells, cell lines, fluids, or tissues. The proposal needs to be highly feasible, should be based on existing assays and involve tools / reagents that are either available or which can be easily produced. We expect that the project will be executed in your laboratory and takes advantage of existing technologies and assays. We will only consider project proposals which can be completed within 18 months or less. Within this period, you should be able to generate confirmation of your hypothesis based on predefined experimental milestones.

Please note that any proposals referring to IL-25 and IL-27 will not be considered (previous annotation error for C19orf10 as described in detail in reference 1).

Proposals that allow identifying MYDGF downstream signaling pathways but are not suited to identify the primary molecular targets of MYDGF.

Projects that are based on technologies that require substantial establishment and validation (no previous hands-on experience) will be deprioritized.

Approaches that use technologies other than classical pull-down methods will be favored.

We are open to all proposals that can fully or partially meet the indicated requirements.

For this call, we commit to a review turn-around until end of January 2021. If your project is selected, you will have the opportunity to directly collaborate with the Research Beyond Borders (RBB) team of Boehringer Ingelheim. You can expect an initial funding of up to 200,000 euros for the prospective collaboration period (maximum 18 months in total). Please note that additional budget would become available, if experimental milestones and Go decision confirmed your hypothesis within the 18 months period.

In addition, Boehringer Ingelheim will provide qualified custom-made biological tools such as human MYDGF as well as mutants with reduced functionality (as exemplified in reference 8) as untagged or tagged versions. Antibodies for MYDGF detection (e.g. Western Blot and ELISA) can be provided as well as MYDGF-expressing or -deficient (knockout) cells.

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) publically and feature them on opnMe.com and our social media channels. We would guide you through this process, and as part of it, we would kindly ask for your upfront consent, in case our scientific jury had selected your answer.

We are seeking research collaboration proposals that contain:

• A well-structured proposal outlining a new and compelling scientific approach to identify and validate MYDGF’s molecular target(s)/ interactor(s).
• 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.
• 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.
• We will only consider project proposals which can be completed within 18 months or less. Within this period, you should be able to generate confirmation about your hypothesis based on predefined experimental milestones.
• 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.

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 confidential 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 have been looking for answers for the following scientific challenge: How do you propose deciphering the molecular targets of human Myeloid-Derived Growth Factor (MYDGF)?

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 December 17, 2020, 11.59 pm PST.