SPARC - FOA Priorities

This webpage serves as the official list of Priorities for the NIH SPARC program's recently posted funding announcement to support critical program needs. Applications must be directly responsive to a specific currently active program Priority. A list of those Priorities is available below. Any new Priorities will be added around the beginning of each month, and at least 30 days’ notice will be provided before a Priority becomes inactive and archived. Check back at the beginning of each month for updates or sign up for the SPARC listserv to be notified when new priorities are posted.

See the Frequently Asked Questions (FAQ) page for common questions and answers.

If you have suggestions for future Priorities, please email NIH-CF_SPARC@mail.nih.gov.

  


 

CURRENT Priorities

OTA-20-004

UPDATE: Application requirements and instructions for these priorities were posted on June 1, 2020. These priorities were posted April 19, 2020. 

Priority: Interoperable, extensible, and personalizable simulations on the o2S2PARC platform to inform bioelectronic medicine development, with particular focus on diseases and conditions that impact the stomach, colon, lungs, heart, or lower urinary tract.

Additional information:

Despite the vast amounts of data and software tools being generated by autonomic/enteric/peripheral neuroscience researchers inside and outside of SPARC, the field currently lacks a comprehensive effort to incorporate anatomical and physiological data into interactive multiscale, multiphysics models capable of predicting how modulation of a given neural target will impact organ functional responses. A range of challenges has so far limited the number and utility of existing computational models:

  • Few existing organ models explicitly consider the role of the nervous system signaling in regulating function.
  • With some exceptions, experimentation and interactive computational model development are performed by individual groups, without awareness to the potential advantages of collaboration.
  • With some exceptions, the generation of experimental data is not driven by the parameter needs of model developers; and subsequently, the model development does not enable the testing and validation of new therapeutic targets and hypotheses.
  • The technical and conceptual heterogeneity of existing computational models renders integration difficult, particularly across species, spatial and temporal scales, and organs.
  • Existing neuroscience knowledgebases and computational resources are underutilized.

 

The NIH SPARC program has supported the development of an online simulation platform, o2S2PARC, for hosting computational models to address these challenges. The SPARC program now seeks to support the development of interoperable models that leverage o2S2PARC to power advanced predictive simulations of neuromodulation interventions and therapeutic outcomes for a range of diseases and conditions.

Examples of projects or project components that support the goals of this funding Priority include but are not limited to:

  • Collaborative efforts between modelers, experimentalists, physician-scientists, and/or other scientific/technical individuals that aim to accomplish and/or facilitate:
    • Identification of novel targets or targeting approaches,
    • Data-driven hypotheses that inform therapies and can be tested and validated experimentally,
    • Generation of working computational models from experimental information, and
    • Extension beyond individual computational models (e.g., connecting disparate models over timescales and systems);
  • Software to identify parameters from existing data in an unsupervised fashion;
  • Models that account for variability and uncertainty across species, individuals, and sexes;
  • Models that are capable of predicting off-target effects; and/or
  • Techniques for identifying underdetermined parameter ranges where future experimental and computational data collection efforts would be most impactful.

 

Requirements

All projects funded under this Priority must adhere to the following requirements. A description of how each requirement is addressed should be included in the full application.

  • The project must integrate with the o2S2PARC online computational platform (see below for additional information). Free and open-source software, programming language(s), and license(s) should be utilized where possible.
  • The effort must inform bioelectronic medicine development for diseases and conditions that impact the stomach, colon, lungs, heart, or lower urinary tract. It should strive to make an impact on neuromodulation therapy development within the next 1-4 years.
  • Existing experimental data and/or knowledge must be utilized to the maximum extent possible — whether from SPARC, the literature, or other resources (e.g., data repositories or knowledgebases).
  • To bolster confidence in models and their predictions, the project must use the Ten Simple Rules for Model Credibility, developed in the IMAG Multiscale Modeling Consortium.
  • To be clinically relevant, simulations should account for variability and uncertainty across species, individuals, and sexes, and should account for off-target effects. (If any of these criteria cannot be met, justification must be provided in the full application.)
  • The project should employ a model-driven design strategy. Model reproducibility approaches should be incorporated in the project, and uncertainty quantification should be addressed in the model development process.

 

Information about o2S2PARC

SPARC’s online computational platform, o2S2PARC, supports collaborative modeling and enables users to share and execute computational simulation, analysis, and visualization modules, as well as to combine these into coupled pipelines. o2S2PARC is being developed by the SPARC Modeling & Simulation Core, funded through an Other Transactions (OT) award to the IT’IS Foundation (OT3 OD 025348).

Teams that are funded under this Priority are expected to actively collaborate with the IT’IS Foundation. Applicants should account for such collaboration in their milestones and budget.

A webinar introducing the o2S2PARC platform can be viewed here: https://www.youtube.com/watch?v=vrdVealYydE

Documentation for o2S2PARC is available here: https://docs.osparc.io/

o2S2PARC demos are available here: https://sparc.science/data?type=simulation

To get in touch with the IT’IS Foundation, or more information about o2S2PARC or to request a free account, please email support@osparc.io.

 

Other Relevant Background and Resources

 

Application Requirements and Timeline

  • UPDATE - Applicants who are invited to submit a full application must meet the application requirements, include a copy of the Invitation to Submit (ItS) and address any feedback provided in the ItS to be considered responsive.
  • UPDATE - Applicants must follow the instructions for submitting full applications through the NIH's Application Submission System & Interface for Submission Tracking (ASSIST). Application components should be included as "pdf" attachments.
  • For projects to be considered for FY2020 funding, concept letters must be submitted no later than June 1, 2020. Concept letters submitted after this date may be considered for future funding (e.g., FY2021), if funds are available.
  • Note: If the Covid-19 global pandemic significantly impacts concept letter submission by the June 1, 2020 deadline, late submissions with justification of Covid-19 impact may be considered for FY2020 funding. However, there is no guarantee that NIH staff will be able to review late submissions and provide invitations to enable application submission by July 1, 2020.
  • Successful concept letters will receive an invitation to submit a full application, which will be due no later than July 1, 2020 to be considered for FY2020 funding. Applications requested beyond this date may be considered for future funding (e.g., FY2021), if funds are available.

 

Expected Duration of Project Period

Project applications can request up to 2 years of support.

 

Application Review Criteria

Utility/Impact

  • How much potential is there for the proposed project to make an impact on neuromodulation therapy development within the next 1-4 years?

Premise

  • To what degree will the proposed project make use of o2S2PARC in a practical and feasible manner?
  • Does the proposed work leverage existing SPARC and/or other data to the maximum extent possible?
  • To what degree does the proposed project employ a model-driven design strategy?
  • To what extent does the application propose to use free and open-source software, programming language(s), and license(s), to the extent possible?

Scientific/Technical Merit

  • To what extent does the application use the Ten Simple Rules for Model Credibility to effectively communicate the model development life cycle?
  • To what degree are model reproducibility approaches incorporated into the proposed project?
  • To what extent is uncertainty quantification addressed in the model development process?
  • How sound, justifiable, feasible, and valid are the proposed plans, methods, techniques, and procedures?
  • How realistic and congruent with the goals of the Priority are the proposed milestones, deliverables, and benchmarks?
  • How suitable is the Resource Sharing Plan?
  • To what extent are anticipated risks and challenges addressed?  How acceptable are the proposed mitigation plans?

Past Performance/Experience

  • To what extent does the proposed project team contain an appropriate combination of domain expertise, e.g. computational scientists, physiologists, clinical experts, etc.?
  • To what degree does the past performance and experience of the Principal Investigator(s) and collaborators, demonstrated by the significance and impact of previous research, publications, data/model sharing, professional activities, awards and other recognition, etc., indicate strong qualifications to lead the project?
  • To what degree is the necessary expertise committed to the proposed research project?
  • If this is a Multiple PD/PI application, how reasonable is the Leadership Plan?

 


ARCHIVED Priorities

RFA-RM-16-003 (previous FOA) 
These Priorities are archived for reference purposes only.

These priorities were posted February 8, 2016.

  • Modification of technologies, such as those previously developed to understand neural circuits in the Central Nervous System, to understand neural circuits in the Peripheral Nervous System; or technology used to understand neural circuits controlling one organ which can be modified for use with another target organ or multiple other organs
  • Sensing techniques for relevant biomarkers to inform closed-loop response systems in organs (e.g., biomolecule sampling/measuring)
  • Technologies for cell-class specific targeting and manipulation in peripheral nerves and ganglia, appropriate for animal models with clinical relevance (e.g., optogenetics)
  • Activity sensors and associated imaging technologies suitable for peripheral nerve and end-organ monitoring (e.g., voltage probes)
  • Reliable, wireless, high density technologies capable of simultaneous recording/stimulation of all neural signals going to and coming from a targeted organ; and or to facilitate functional mapping between multiple organs and nerves
  • Biomimetic or biologically-active interfaces for chronic implants of electrodes and sensors that enhance our ability to chronically study the function of a target organ
  • Invasive and non-invasive technologies for tunable stimulation/inhibition/block of nerve activity (e.g., ultrasound, magnetic fields, etc.)
  • Tools for non-invasive tracing and functional imaging to facilitate minimally invasive surgeries in humans and anatomical mapping
  • Computational platforms and predictive models that generate testable hypotheses of autonomic nervous system control of organs

RFA-RM-17-009 (previous FOA)
These Priorities are archived for reference purposes only.

These priorities were posted March, June and September, 2017.

  • Imaging and targeting:
    • Quantitative imaging and analysis techniques for PNS and/or organ tissue
    • Contrast agents to identify variability due to individual subject differences in either neuroanatomy or neurophysiology
    • Whole-body imaging of neural tracts (in vivo or ex vivo); the ex-vivo approaches may be destructive or non-destructive to the tissue
    • Fascicular tracing/targeting (i.e., methods to increase contrast, biochemical, surgical, and/or viral)
    • Fiber type targeting (i.e., methods to ligate an imaging agent, biochemical, surgical, and/or viral); this includes plexi, unbundled nerves, and/or vascular nerves
    • Methods to assess blood flow within microvasculature of nerves and ganglia. Of particular interest are methods that can observe blood flow under electrodes
    • Non-invasive imaging tools to locate and characterize isolated ganglia and/or nerve branches
    • Organ preparation and/or methods to image neural junctions/terminals in an organ of interest
    • Phantoms to support development of new imaging technologies for neuroanatomy
    • Real-time localized sensing and/or imaging of neurotransmitter release and/or uptake in the PNS
    • Adaptation of stitching, segmenting, and tracing software to PNS and organ datasets
    • Adaptation of biomechanical, biochemical, and bioelectrical models of organ function for use in studying the impact of neuromodulation on organ function
    • Computational models to assess safety limits of stimulation and/or blocking of neural activity (e.g. biophysics and regulatory science for neural interfaces)
    • Biophysical models of electrical neuromodulation that predict selective activation or block specific fiber types and locations. These computational models should be predictive of side effects (i.e. other fibers that may be activated or blocked)
    • Methods to enhance spatial resolution and/or selectivity for fiber types, fascicles, plexi, or ganglia that do not rely on genetic manipulation or transfer (e.g., methods to ligate an imaging agent, enhance contrast, or selectively activate nerve components without genetic manipulation or transfer)
  • Modeling and simulation:
    • Computational models to assess safety limits of stimulation and/or blocking of neural activity (e.g. biophysics and regulatory science for neural interfaces) with or without model validation in vivo
    • Computational models of neuromodulation that incorporate variability due to individual subject differences
    • Biophysical models of electrical, infrared, or ultrasonic neuromodulation that predict selective activation or block specific fiber types and locations. These computational models should be predictive of side effects (i.e. other fibers that may be activated or blocked)
    • Adaptation of stitching, segmenting, and tracing software to PNS and organ datasets
    • Adaptation of biomechanical, biochemical, and bioelectrical models of organ function for use in studying the impact of neuromodulation on organ function
    • Computational models for non-invasive nerve stimulation technologies (e.g., TENS) to provide higher spatial resolution and/or fiber-type specificity. Models must be validated in vivo
  • Surgical:
    • Surgical tools to safely find and/or access nerves, fascicles, and/or ganglia/plexi (e.g. imaging, protocols, etc)
    • Surgical phantoms
    • Real-time in-vivo methods to determine if the PNS is damaged during surgery
    • Methods to repair PNS damage after implant of a neural interface
    • Surgical tools to safely find, access, and/or attach interfaces to nerves, fascicles, and/or ganglia/plexi (e.g. imaging, protocols, etc)
  • Interfacing:
    • New approaches to neuromodulate the PNS that are inherently safe, have high specificity (temporal, spatial, fiber type), and are minimally or non-invasive. 
    • Blocking must be reversible. 
    • Potential approaches might include biologically derived methods to interface with the PNS in vivo, such as artificial biologic constructs, hydrogel-encapsulated cells, or engineered tissue grafts
    • Multi-modal (e.g. optogenetic and electrical) neural interfaces that provide greater specificity than a single-mode interface
    • Adaptation of signals engineering approaches to increase spatial and temporal precision of existing multichannel neuromodulation technologies. For example, applying inverse transform or phased array methods to an existing nerve cuff 
    • Distribution of existing neuromodulation systems to the SPARC consortium. While some adaptation may be required to build interfaces for SPARC1 or SPARC3 investigators, the emphasis of this priority is on the manufacture, distribution, training, and support for these technologies and the associated surgical methods to implant them in nerves, ganglia, or plexi 
    • Adaptation and safety testing of existing systems for use in large animal models or humans. Systems should provide high-specificity neuromodulation of the PNS or assess end-organ function 
    • Biosensors to detect end-organ function biomarkers
    • Methods to identify and understand chronic PNS tissue damage after implant of a neural interface
    • Surgical tools to safely find, access, and/or attach interfaces to nerves, fascicles, plexi, and/or ganlgia (e.g., imaging, surgical protocols, etc.) - This Priority only supports development of surgical tooling and methods, not development of new interfaces
    • Methods for performing electrophysiological recordings during MR imaging
    • Enhancement of FDA-cleared or approved non-invasive nerve stimulation technologies (e.g., TENS) to provide higher spatial resolution and/or fiber-type specificity
  • Sample preparation priorities:
    • Transgenic large animal models to facilitate imaging/targeting or interfacing with peripheral nerves and/or end organs
    • Methods for accessing and patch clamping ganglia, plexi, and small nerves. This may include techniques for enzymatic digestion or robotic automation of access to dissociated ganglia
    • Optimization of techniques to label human peripheral nerves and/or end organs. This may include new antibodies, fluorophores, or image processing algorithms to improve immunohistochemical analysis of small nerves or nerve-organ junctions
    • Organ preparation and/or methods to image neural junctions/terminals in an organ of interest
  • Services provided to all SPARC consortium members:
    • Large-scale high-resolution image capture of ex vivo specimens (e.g. TEM, X-ray, or light sheet)
    • Device testing (e.g., mechanical, electrochemical, toxicity, accelerated life, ISO 10993 or equivalent)
    • ASIC design, development, and validation
    • Packaging and encapsulation, or interconnects suitable for >6 month animal trials or human use
    • Genetics services (e.g., RNA-seq, viral vector development, and transgenic line generation)
    • Distribution of existing neuromodulation systems to the SPARC consortium. While some adaptation may be required to build interfaces for SPARC1 or SPARC3 investigators, the emphasis of this priority is on the manufacture, distribution, training, and support for these technologies and the associated surgical methods to implant them in nerves, ganglia, or plexi 
  • Animal and tissue preparation priorities:
    • Genetic approaches for large animals to facilitate imaging/targeting or interfacing with peripheral nerves and/or end organs (e.g., transgenic models, viral vectors, etc.)
    • Methods for accessing and patch clamping ganglia, plexi, and small nerves. This may include techniques for enzymatic digestion or robotic automation of access to dissociated ganglia
    • Optimization of techniques to label human peripheral nerves and/or end organs. This may include new fluorophores or image processing algorithms to improve immunohistochemical analysis of small nerves or nerve-organ junctions

This page last reviewed on June 9, 2020