Description:
382 Integrated Subcellular Microscopy and ‘Omics in Cancer Cell Biology
Fast track proposals will be accepted. Number of anticipated awards: 2-3 Budget (total costs, per award): Phase I: up to $300,000 for up to 9 months; Phase II: up to $2,000,000 for up to 2 years
PROPOSALS THAT EXCEED THE BUDGET OR PROJECT DURATION LISTED ABOVE MAY NOT BE FUNDED.
Summary
Advances in microscopy have improved the ability to resolve, describe, and quantify subcellular anatomic structures, organization, and dynamics. Concurrently, single-cell molecular ‘omics technologies have revolutionized our understanding of intracellular processes and intercellular communication. Recent NIH/NCI programs, such as the Physical Sciences-
Oncology Network, the 4-D Nucleome Program, and the Human Tumor Atlas Network, aim to understand cancer from multiple orthogonal perspectives, including employment of technologies such as high-resolution microscopy and multiscale ‘omics. However, experimental or computational methods that facilitate true integration of advanced high-resolution cellular and subcellular microscopy and multi-scale molecular ‘omics technologies are not readily available to the research community. Technologies that offer such integration will facilitate multidimensional spatially preserved mapping of the tumor ecosystem, leading to a broader understanding of tumor heterogeneity, the role of cell-cell and/or cell-matrix interactions in the response to cancer therapy, and will provide data for building predictive computational models of cancer initiation, progression, metastasis, and response to treatment.
Importantly, recommendations of the Cancer Moonshot Blue Ribbon Panel call for technology-based deliverables that combine approaches from disparate fields, such as imaging at the cellular to subcellular scales with single cell "-omics" approaches. It is anticipated that the innovation in the small business sector, can provide instrumentation and enabling technologies to serve the basic cancer biology research needs. NCI currently supports grants within the IMAT portfolio that are poised to respond to such a solicitation. While there are current efforts to promote small business activity within the single-cell analysis community, this proposal offers a complimentary, but distinct, opportunity through its focus on directly linking cellular phenotypes measured through high-resolution cellular and sub-cellular microscopy with multi-scale ‘omics measurements.
These needs include (but are not limited to) technologies that enable:
• multidimensional coupling of subcellular-to-cellular imaging modalities with orthogonal -omics and physicochemical measurement approaches;
• combination of spatial and temporal imaging at the super-resolution scale with phenotypic processes at the cellular scale;
• subcellular mapping and molecular characterization of individual cells in tumor tissue sections that informs on clonal evolution dynamics and heterogeneity;
• determination of subcellular dynamics coupled with computational methods to examine drug response and cancer cell resistance;
• analysis of subcellular processes in cancer that inform on cell phenotypes within the microenvironment or in the context of tissue relevant niches;
Advances in pre-clinical research in these areas have the potential to be translated into new methods to aid the detection and diagnosis of cancer, and to guide clinical decisions. Commercialization of the research tools supported by this contract solicitation will enable a broader community of researchers to engage in these studies, and thus increase the rate of scientific progress in this field.
Project Goals
Projects to be supported under this FOA will support the broader goal of developing an infrastructure to accelerate the microscopy-omics community and enable transformative research in cancer cell biology, diagnostics, or monitoring strategies.
The short-term goal of this FOA will be to stimulate innovation that integrates cellular imaging modalities with technologies that provide single cell -omics level data (e.g. genomic, transcriptomic, proteomic, etc.) that are relevant to cellular processes that are disabled or exploited in cancer. Projects supported by this contract solicitation should enable multidimensional interrogation of cancer cell biology in a manner that combines the spatial-temporal strengths of imaging modalities with complementary orthogonal measurements achieved through -omics and physicochemical approaches.
This solicitation seeks to encourage the development of new imaging platforms, probes, or a unique combination of platforms with image-based approaches that leverage a multidimensional perspective of cancer cell biology. It is anticipated that that projects may include the development of new algorithms or software that facilitates image analysis or multimodal data analysis to render an understanding of cancer cell biology from a multidimensional perspective; however, applications that are solely software based would not be responsive.
Phase I Activities and Deliverables
Phase I activities should generate data to confirm the feasibility and potential of the technology(ies) to combine microscopy at the subcellular scale with orthogonal cell "-omics" and physicochemical measurement approaches.
Offerors will need to:
1. Define the cancer biology application the platform(s), device(s) or combined device-computational approaches addresses.
2. Generate proof-of-concept data in a generally accepted cancer cell model system with the means to sense, interrogate, detect or resolve and map spatial cellular anatomy and/or dynamics using microscopy or other imaging modalities with micro- to nano-scale resolution.
3. Demonstrate feasibility of integrating the imaging modality(ies) in Phase I Deliverable #2 with orthogonal assessments at the molecular scale (such as genomic, proteomic, metabolomic, or epigenomic analyses), physicochemical scale (such as redox, pH, force/stiffness), and/or functional scale (such as proliferation, transformation, motility, invasion, resistance, or cell death) to generate multidimensional data. Offerors should specify quantitative technical and commercially-relevant milestones, that can be used to evaluate the success of the tool or technology being developed. Offerors should also provide appropriate justification relevant to both the development and commercialization of these technologies.
Quantitative milestones may be relative metrics (e.g. compared to benchmarks, alternative assays) or absolute metrics (e.g. minimum level of detection)
Phase II Activities and Deliverables
Phase II activities should support the commercialization of the proposed technology and include the following activities:
1. Demonstrate reliability, robustness and usability in basic and/or clinical cancer research.
2. Demonstrate system performance and functionality against commercially relevant quantitative milestones Offerors should specify quantitative technical and commercially-relevant milestones, that can be used to evaluate the success of the tool or technology being developed. Offerors should also provide appropriate justification relevant to both the development and commercialization of these technologies
Quantitative milestones may be relative metrics (e.g. compared to benchmarks, alternative assays) or absolute metrics (e.g. minimum level of detection)
3. Demonstrate utility with benchmark experiments obtained across a range of generally accepted cancer cell model systems.
4. Show feasibility to be scaled up at a price point that is compatible with market success and widespread adoption by the basic research community.
