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US National Institutes of Health – Metabolic Reprogramming to Improve Immunotherapy (R01 Clinical Trials Not Allowed) – PAR-16-228
Sponsor: US National Institutes of Health 		Closing Date: 05-Oct-2018
The overall goal of this funding opportunity announcement (FOA) is to encourage R01 grant applications to (a) generate a mechanistic understanding of the metabolic processes that support robust anti-tumor immune responses in vivo, (b) determine how the metabolic landscape of the tumor microenvironment affects immune effector functions, and (c) then use this information to manipulate (reprogram) the metabolic pathways used by the tumor, the immune response, or both to improve cancer immunotherapy.

Applicable research directions could include, but not be limited to, the following:
Major Challenges and Opportunities:
- Assess the crosstalk between the different metabolic platforms that may be operating in any given cell and integrate those assessments to generate a more complete metabolic profile at the single cell level.
- Generate a better understanding of metabolites as signaling molecules in transcription that effect cellular differentiation.
- Determine the relationship between metabolism and self-renewal capacity.
- Clarify how specific metabolites affect various immune states such as activation, anergy, development of long-lived memory cells versus short-lived effector cells, and homing to their proper niche.
- Elucidate how the metabolic environment (or nutrient repertoire) in normal tissues, immune tissues, and in the setting of pathology (in tumors) affects immune cell development and/or effector function.
- Delineate the consequences of metabolic interventions on immune cell growth and effector functions.
Tools and Technologies:
- New instrumentation and novel approaches are needed to parse the metabolic heterogeneity of tissues in situ.
- Improved methods and approaches need to be developed to assess how the metabolic characteristics of the tumor microenvironment affect the anti-tumor immune response.
- Computational models to better understand which metabolic pathways are hard-wired and when perturbed lead to cell death and which are flexible and can be experimentally manipulated need to generated.
- Development of small molecule inhibitors of glycolysis, FAO, and other metabolic pathways for therapeutic intervention is needed.
- The ability to perform comprehensive analysis of the metabolic heterogeneity (metabolic flux/metabolomics) of different immune subsets and a full description of the functional consequences of differential utilization of metabolic pathways in supporting immune cell differentiation is needed.

Eligibility
• Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
• Applications from Foreign Organizations: Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

Funding
• Application budgets are not limited but need to reflect the actual needs of the proposed project. Applicants requesting USD $500,000 or more in direct costs in any year (excluding consortium F&A) must contact a Scientific/Research Contact at the NIH at least 6 weeks before submitting the application.
• The project period may not exceed 5 years.

Please see the Funding Opportunity Announcement for further information. Applications may be prepared and submitted via the NIH ASSIST system or Grants.gov. For complete instructions, you must refer to both the NIH Application Guide and the Funding Opportunity Announcement (FOA), noting that instructions in the FOA take precedence over the Application Guide.

Key Dates
Letter of Intent (non-mandatory) due to NIH: Not Applicable
Applications due to UQR&I: 24 September 2018
Applications close with NIH: 5 October 2018, 5:00pm local time of applicant organisation
Future application closing dates: Standard dates apply until expiry
Expiration date of FOA: 8 September 2019

Ahead of internal review, ensure all online components on ASSIST or Grants.gov are complete. To initiate review, email your completed Funding Application Coversheet to internationalgrants@research.uq.edu.au. Interested applicants are strongly encouraged to make contact with the UQR&I international team (via internationalgrants@research.uq.edu.au) well in advance of the UQR&I internal deadline to discuss their application.
Website: https://grants.nih.gov/grants/guide/pa-files/PAR-16-228.html

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