The purpose of this funding opportunity announcement (FOA) is to invite applications for Physical Science-Oncology Projects (PS-OP). The goal of the PS-OPs is to promote a ‘physical sciences perspective’ of cancer and foster the convergence of physical science and cancer research by forming transdisciplinary teams of physical scientists (e.g., engineers, physicists, mathematicians, chemists, computer scientists) and cancer researchers (e.g., cancer biologists, oncologists, pathologists) working very closely together to advance our understanding of cancer biology and oncology. The transdisciplinary nature of the Projects will require the formation of small collaborative research teams around a physical sciences-based framework to address fundamental questions in cancer research. The PS-OPs will develop and test physical sciences-based experimental and theoretical concepts that complement and advance our current understanding of cancer. The PS-OPs, individually and along with other PS-OPs and the Physical Sciences-Oncology Centers (PS-OC), will form the Physical Sciences-Oncology Network (PS-ON). The Physical Sciences-Oncology initiative is expected to further develop emerging fields of study in cancer that are based on physical sciences principles and approaches.
The Network will include both the PS-OP U01s (this FOA and PAR-15-021) and the PS-OC U54s (PAR-14-169). This PS-OP FOA provides opportunities for teams with the necessary expertise to address specific, focused cancer research questions from a physical science perspective or approach. Investigators from both the PS-OPs and PS-OCs will be expected to collaborate and share data and expertise across the Network and participate in collaborative Network activities and annual meetings. The aim of the PS-ON is to integrate physical sciences perspectives into cancer research to complement and expand our current understanding of cancer biology across many biological length-scales and time-scales, with the goal of improving cancer prevention, detection, diagnosis, prognosis, and therapy.
In 2009, the NCI launched the PS-OC Program, a network of 12 Centers investigating complex and challenging questions in cancer research from a physical sciences perspective (http://pson.cancer.gov). Each Center conducted transdisciplinary research integrating the perspectives of physicists, mathematicians, chemists, engineers, computer scientists, cancer biologists, and oncologists to examine cancer biology using approaches and theories from the physical sciences. The first phase of the PS-OC Program through 2015 generated several discoveries and made steady progress towards its scientific and programmatic goals. Highlights of research advances made by the PS-OCs include: 1) understanding mechanisms behind the generation of mutations in cancer genomes based on 3-D architecture and polymer physics, 2) optimizing dosing strategies for lung and brain cancer treatment using computational physics and evolutionary theory, and 3) progress in understanding the role of mechanics in tumor progression and metastasis using physical parameters.
To explore how the NCI can continue to strategically support the integration of physical sciences and cancer research, a Think Tank and series of Strategic Workshops were held in 2012 to assess the progress of the PS-OC Program and to identify areas that merited continuation or required additional support. These workshops brought together experts from the fields of physical sciences, engineering, mathematics, cancer biology, clinical oncology, developmental biology, and others, with approximately 75% of participants from outside of the PS-OC Program. The workshops served to update the challenges and opportunities at the interface of physical sciences and cancer research and refine the thematic areas and fundamental questions that would benefit from an integrated transdisciplinary approach. Information from these workshops as described in the workshop reports helped shape the scientific and structural elements of the ongoing PS-ON program, which includes the U01 collaborative research Projects (PS-OP) and the U54 Centers (PS-OC).
The aim of the PS-ON is to integrate physical sciences and cancer research perspectives and approaches to address complex and challenging questions in cancer research. This FOA for PS-OPs invites a broad range of research that addresses important cancer questions from a physical sciences perspective. Applicants may focus on one of the suggested thematic areas, other physical sciences-based thematic areas, such as the role of evolutionary theory in cancer or de-convoluting the complexity of cancer, or integrate multiple thematic areas into a discrete, specified, circumscribed collaborative U01 research project.
Potential areas of investigation include but are not limited to those described below.
Understanding and applying physical science perspectives and approaches to cancer biology and oncology can cover a variety of topics and areas of research. While the research topics are not limited, the following represents two examples of research areas and questions that could be framed within an application.
The Physical Dynamics of Cancer: Traditionally, cancer is thought of primarily as a genetic disease that is modulated by biochemical cues from the tumor and microenvironment. However, physical properties across many biological length-scales (e.g., subcellular, cell, tissue, organ, whole organism) also play an important but poorly understood role. This physical perspective can be integrated with the molecular and genetic understanding of cancer to generate a more comprehensive view of the complex and dynamic multiscale interactions of the tumor-host system. Physical properties such as mechanical cues, transport phenomena, bioelectric signals, and thermal fluctuations can modulate the behavior of cancer cells, the microenvironment, tumors, and the host. In developmental biology, studying how these physical factors regulate embryogenesis and tissue patterning has augmented existing approaches and knowledge. Techniques from the physical sciences can be used to measure physical properties of single cells, discrete multicellular structures, and tissues. These measurements can be integrated with orthogonal data using high-dimensional analysis and computational physics models to complement current approaches and potentially identify new physical properties that could be exploited for understanding the biology of cancer. Potential questions to be addressed include, but are not limited to:
- What are the physical origins of genomic instability and mutagenesis in relation to the energetics of protein-DNA interfaces and packaging, dynamic epigenetic states, and higher-order genome organization? How do these physical parameters affect initiation, progression, or response to treatments and can these physical features be exploited for potential diagnosis or prognosis?
- How do physical properties and mechanics of tumors, disseminating cells, and sites of colonization and metastasis contribute to metastasis and dormancy? How do these factors affect cancer progression and evolution of therapeutic resistance?
- How can physical properties such as forces serve as biomarkers or signatures that can be used to evaluate a metabolic state or be an (early) indicator of the disease?
- What roles do the physical properties of tumor systems play in the bidirectional communication between tumor and host? How do changes in these properties or their gradients contribute to metastatic processes or dormancy?
Spatio-Temporal Organization and Information Transfer in Cancer: Appropriate spatial and temporal organization of structures across many biological and physical length-scales (e.g., subcellular, cell, tissue, organ, whole organism) and time scales is required for managing the transfer of information that is critical for regulated growth. For example, cells must position billions of molecules in the right place and time to facilitate the proper function of signaling pathways and complexes. Additionally, cells regulate the size, number, and spatial distribution of organelles, and the three-dimensional architecture of the genome and nucleus. Intrinsic and extrinsic factors in turn regulate the size, shape, and heterogeneity of tissues. Metastasis occurs on a system level and the dispersion and dissemination of tumor cells depends in part on the architecture of both primary and metastatic sites. Disruption of spatial and temporal organization at each of these scales is associated with the development and progression of cancer and may influence the evolution of therapeutic resistance. Techniques and perspectives from the physical sciences are particularly well suited to exploring the complexity of these multiscale processes. For instance, advanced imaging and analysis techniques facilitate measurements at scales ranging from subcellular to tissue-level with a high degree of spatial and temporal precision. These approaches can be augmented using tissue mimetics or three-dimensional tissue engineering tools; and, computational physics models or evolutionary theories can be used to integrate data across scales and iteratively inform subsequent studies. Potential questions to be addressed include, but are not limited to:
- How is the spatial organization of the nucleus and other organelles modulated by extrinsic physical factors? How do changes in organelle organization affect initiation and progression of cancer? How can these alterations in spatial organization be exploited for cancer detection or prognosis?
- Using physical science approaches such as those mentioned above, how do the dynamics of molecular and cell crowding, phenotypic variation, cell population diversity, and extracellular matrix mechanics and vascular architecture in tumors affect cancer initiation, progression, metastasis, and response to treatment?
- How can the evolutionary dynamics of therapeutic resistance be examined in the context of dynamic spatio-temporal environments (e.g., oxygen, drugs, nutrients, tissue mechanics) to better define mechanisms of progression and resistance and develop alternative therapeutic strategies?
- How can we better understand information flow in cancer within individual cells, among different cell populations, and at a patient scale and using approaches such as nonlinear feedback systems, game theory, control theory and/or machine learning/artificial intelligence?
- How do we study, quantify, integrate, and model the complexity of tumor development across multiple length- and time-scales? That is, how do changes at the molecular and cellular level affect the overall development, structure, and organization of a tumor and vice versa?
The above examples of possible research directions are not meant to be comprehensive.
Organization of Individual PS-OPs and the PS-ON
PS-OP Expertise: Due to the transdisciplinary nature of the projects and the focus on collaboration and expertise sharing, this FOA strongly encourages the use of the multi-PD/PI option with a small team of combined expertise from the physical sciences and cancer research. When applicable, additional PD/PIs, key personnel, and collaborators should consist of a transdisciplinary research team with complementary abilities organized around a scientific framework to address fundamental question(s) in cancer research. It is recognized that there may be instances where a single PD/PI will already have the combined expertise to bring a physical science perspective to study an important problem in cancer research and may not need to use the multi-PD/PI option.
PS-OP Requirements: PS-OP applications should propose a single, cohesive project. Applications proposing multiple projects are not appropriate for this FOA.
In addition, the following types of projects are not considered to be of high programmatic priority for this FOA:
- Projects which do not involve a clear, well-integrated physical sciences perspective or approach to the cancer research question
- Projects focused on the development of nanotechnologies, microscopic or radiomic imaging modalities for cancer research should consider the FOA(s) offered by the NCI Innovative Molecular Analysis Technologies (IMAT) Program or the Cancer Imaging Program (CIP)
- Projects focused on emerging questions in cancer systems biology should consider the FOA(s) offered by the NCI Cancer Systems Biology Consortium (CSBC) Program
- Projects focused on the development of informatics technology should consider the FOA(s) offered by the NCI Informatics Technology for Cancer Research (ITCR) Program.
PS-ON Organization: The PS-ON will consist of all funded PS-OP U01 Research Projects and PS-OC U54 Research Centers and be governed by the PS-ON Steering Committee. Collaborative Network activities, such as Trans-Network Projects, will allow PS-OPs and PS-OCs to cross-test ideas, integrate diverse data sets, and validate (or refute) theoretical, experimental, or translational models. Trans-Network Projects are small research projects aimed at a question in cancer-relevant biology from a physical sciences perspective that could be addressed by leveraging the expertise and investigators from multiple PS-OPs and/or PS-OCs. Topics and formats for Trans-Network Projects will be defined by the PS-ON Steering Committee. Investigators may propose a new or revised Trans-Network Project one or more times per year, as determined by the PS-ON Steering Committee and NIH Staff. Trans-Network projects are not required to be described in the grant application.
NCI will hold a pre-application informational webinar for this FOA. Date, time, and other details will be posted at http://pson.cancer.gov.
Deadlines: January 30, 2019; July 30, 2019; January 30, 2020; July 30, 2020 (letters of intent due 30 days prior to deadline)
Filed Under: Funding Opportunities