ASPIRE Award 2025 Request for Proposals

Intrinsically Disordered Proteins and Cancer

The revolutions in cryo-electron microscopy and artificial intelligence have profoundly transformed our understanding of protein structure and function over the past decade. Despite this progress, more than 30% of the human proteome is predicted to consist of intrinsically disordered proteins (IDPs). These enigmatic proteins, lacking a fixed three-dimensional structure, remain less understood compared to their structured counterparts, even though they play pivotal roles in diverse biological processes. This knowledge gap is particularly pronounced in the context of IDPs associated with cancer initiation, development, and progression. Many key driver genes implicated in different tumor types encode IDPs, and a wide array of IDPs contribute to cellular pathways that promote and sustain tumor growth. However, comprehensive research into these proteins has been limited, presenting both a challenge and an opportunity to deepen our understanding of cancer biology and uncover novel therapeutic strategies.

To address this, The Mark Foundation for Cancer Research is soliciting proposals through its ASPIRE Award program, specifically targeting projects focused on IDPs and cancer. These proposals should aim to enhance our understanding of the molecular mechanisms underlying IDP functions in tumor initiation, development, and progression. Additionally, projects may explore the diagnostic and therapeutic potential of IDPs, including the development of innovative methods to target these complex proteins, thereby leveraging their untapped potential in cancer treatment.

The application process will begin with a letter of intent stage consisting of a 2-page description of the project. The portal for the letter of intent is currently open, and letters are due on Tuesday, February 28. Invitations for full applications will be issued in March 2025.

Program Scope

  • Proposed projects must address intrinsically disordered proteins (or intrinsically disordered regions within proteins) and cancer, with a particular focus on understanding the biochemical and biophysical mechanisms of IDPs in cancer progression.
  • Technology development for studying IDPs may be in scope, but the connection to cancer biology must be clear.
  • Projects focused on ordered regions within an otherwise largely disordered protein are ineligible (as a rule of thumb, this encompasses domains with experimentally determined structures or regions with average per-residue model confidence score (pLDDT) above 70 in AlphaFold predictions)
  • Drug discovery projects are not a fit for this program. Developing or expanding methods for targeting IDPs may be part of the experimental plan, but screening campaigns (experimental and virtual) and lead optimization of existing compounds against known targets are not in scope.

Grant Terms

  • Applicants may request funding to support a total budget up to $250,000 for a period of up to 12 months.
  • The budget and duration requested for the grant must match a realistic estimate of the cost and timeline for the proposed work.
  • The budget limit includes both direct and indirect costs, with indirect costs not to exceed 10% of the direct costs.
  • Co-investigators are permitted.
  • Revenue-sharing terms will apply.
  • Additional considerations for clinical research awards:
    • No more the 25% of the total budget may be used to defray clinical trial costs such as research nurses, data management, IRB fees, and database development.
    • Funds will not be released until the protocol has the necessary institutional approvals.

 

Eligibility

  • Applications will be accepted from non-profit institutions worldwide.
  • Principal investigators must be independent researchers at their respective institutions.
  • Researchers are limited to submitting one application as a principal investigator but may be co-investigators on other proposals without limitation.

Key Dates

January 21: Letter of intent portal opens
February 28, 2025: Letter of intent submission deadline
March 2025: Invitations to submit full applications
August 2025: Anticipated award start date

Letter of Intent Guidelines

The Letter of Intent can be a maximum of two pages, including any references, figures, or tables. The PDF must contain the following information:

  • Project title
  • Brief abstract (less than 200 words)
  • Problem statement describing unmet need and opportunity to enable substantial and differentiated impact for cancer research and cancer patients
  • Synopsis of research plan, including key feasibility or proof-of-concept question(s) to be answered, methods overview, and list of specific aims
  • Statement of innovation

Full applications will be accepted by invitation only after review of Letters of Intent. Additional guidelines will be provided to invited applicants.

Contact us at grants@themarkfoundation.org with any questions.


Apply Here

ASPIRE Program Overview

The Mark Foundation for Cancer Research ASPIRE Awards are designed to enable innovative approaches to solving high-impact problems in cancer research that tend to fall outside the scope of other funding opportunities. These awards will be used to support high-risk, high-reward projects with research plans designed to answer key feasibility and proof-of-concept questions in an accelerated timeframe, typically one year. Projects that successfully demonstrate feasibility may be selected to apply for additional funding in a second phase to further develop their innovative concepts and increase the speed to impact for cancer patients.