Notice of Intent to Publish a Funding Opportunity Announcement for RNA Modifications Driving Oncogenesis (RNAMoDO; U01 Clinical Trial Not Allowed)

Key Dates

None

National Cancer Institute (NCI)

The National Cancer Institute (NCI) intends to publish a Notice of Funding Opportunity (NOFO) to solicit applications for the RNA Modifications Driving Oncogenesis (RNAMoDO) Initiative. It aims to promote mechanistic research in the emerging area of RNA modifications that drive oncogenesis, with a focus on the central role of RNA modifications in translational reprogramming of cancer cells.

RNA modifications have been recognized to exert a substantial impact on gene expression and function and their de-regulation has been linked to the cancer phenotype. In particular, recent insights point to a crucial role for mRNA, tRNA, and rRNA modifications in translational reprogramming during tumor initiation, progression, and adaptation to therapy. However, the molecular mechanisms underlying this reshaping of the translatome caused by dynamic changes in RNA modifications, and especially the interplay between different RNA modifications within and across RNA molecules during translation, are not understood and represent the focus of this initiative. Historically, the research community has largely pursued investigations of RNA modifications by studying single RNA species and modification types. However, elucidating how dysregulation of mRNA, tRNA, and rRNA modifications reprograms translation to drive oncogenesis is not likely feasible for any single research laboratory, but will require the combination of expertise in mRNA, tRNA and rRNA biology, translational regulation, and cancer research. To stimulate progress in this emerging field, the RNAMoDO program will support collaborative research projects, preferably using an MPI structure, on how modifications in mRNA, tRNA, and rRNA molecules can drive the oncogenic process through translational reprogramming. To be responsive to the NOFO, each project will also explore the impact of interactions between modifications residing on the same or different RNA molecules during translation.

This Notice of Intent to Publish (NOITP) is being provided to allow potential applicants sufficient time to develop meaningful collaborations and responsive projects.

The NOFO is expected to be published in the early Fall of 2024, with an expected application due date in November 2024. The NOFO will utilize the U01 mechanism for “Research Project Cooperative Agreement (Clinical Trial Not Allowed)”.

Potential applicants are encouraged to view the presentation of this initiative to the NCI Board of Scientific Advisors (BSA), available at: (https://videocast.nih.gov/watch=54423) beginning at 1 hour, 32 minutes, 52 seconds. Presentation slides are downloadable at https://deainfo.nci.nih.gov/advisory/bsa/0324/Maas.pdf.

 

This Notice encourages teams of investigators with expertise and insights into RNA modifications, tRNA, mRNA, and rRNA biology, translational regulation, and cancer research to begin considering their research projects and potential collaborations that can be responsive to this new NOFO.

Examples of responsive research questions include, but are not limited to:

• What are the mechanisms by which biochemical and structural changes caused by modifications in mRNA, tRNA, and rRNA and their interactions contribute to ribosomal heterogeneity in the pre-cancerous state, or during cancer initiation and progression?
• How do different kinds of RNA modifications (within the same or distinct RNA molecules) synergistically or antagonistically interact and combine to alter the properties of RNAs in relation to translational regulation in cancer?
• How do dynamic modifications in mRNA, tRNA, and rRNAs and their interactions alter translation to drive the adaptation of precancerous and tumor cells to cellular stress, such as genomic mutations, hypoxia or chemotherapeutics treatment?
• How do coordinated changes in RNA modifications that drive oncogenesis through translational reprogramming create targetable vulnerabilities?
• How do combinations of dysregulated RNA modifiers (synergistically, or antagonistically) drive 
  translational reprogramming in cancer?
• Are there common mechanisms of crosstalk between RNA modifications during translation in normal cells that become drivers of specific cancer types when dysregulated?
• How can RNA modification mapping and detection approaches be adapted for investigation of crosstalk between modifications driving translational plasticity in cancer initiation and progression?
• Do combinations of RNA modifications in mRNA, tRNA, and rRNA affect the normal and cancer-promoting activity of translation factors during initiation, elongation, or termination of translation?
• Bioinformatics, computational, structural, or systems biological studies that integrate mRNA, tRNA, and rRNA modification data with proteomic studies in cancer to unravel interactions between modifications that drive oncogenesis.

The RFA will be open to all qualified applicants, including new and early-stage investigators, who can establish and lead a collaborative research project to enable the fulfillment of the intended program goals. Applications that examine how any of the above topics contribute to health disparities are welcome and encouraged.

More details will be outlined in the forthcoming NOFO. Applicants are strongly encouraged to consult with NCI staff when developing plans for an application.

Funding Information

Public/State Controlled Institution of Higher Education
Private Institution of Higher Education
Nonprofit with 501(c)(3) IRS Status (Other than Institution of Higher Education)
Small Business
For-Profit Organization (Other than Small Business)
State Government
Indian/Native American Tribal Government (Federally Recognized)
County governments
Independent school districts
Public housing authorities/Indian housing authorities
U.S. Territory or Possession
Indian/Native American Tribal Government (Other than Federally Recognized)
Regional Organization
Eligible Agencies of the Federal Government

Applications are not being solicited at this time. 

Inquiries

Please direct all inquiries to:

Stefan Maas, Ph.D.
National Cancer Institute (NCI)
Email: stefan.maas@nih.gov