Technical Assistance Webinar February 9 2022 Presented by Leslie K Derr PhD NIH HEAL Initiative and Helping to End Addiction Longterm are service marks of the US Department of Health and Human Services ID: 934644
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RFA_AR-22-009HEAL Initiative: Restoring Joint Health and Function to Reduce Pain (RE-JOIN) Consortium (UC2 Clinical Trial Not Allowed) Technical Assistance Webinar
February 9, 2022
Presented by: Leslie K. Derr, Ph.D.
NIH HEAL Initiative and Helping to End Addiction Long-term are service marks of the U.S. Department of Health and Human Services.
Slide2A few logisticsThis meeting is being recordedPlease keep yourself muted QuestionsPost in chat Click chat and post to Everyone Raise your handClick on “Reactions” and select “Raise Hand”
Slide3NIH HEAL Initiative – Helping to End Addiction Long-term Improving Treatments for Opioid Misuse and Addiction Enhancing Pain Management Understanding the Biological Underpinnings of Chronic PainAccelerating the Discovery and Development of Non-Addictive Treatments for Pain https://heal.nih.gov/
Slide4RE-JOIN GoalDefine the innervation of the different articular and peri-articular tissues that collectively form the joint (including bone, cartilage, synovium, joint capsule, ligament, tendon, fascia and muscle), by sensory neurons that mediate the sensation of pain.
Slide5Sensory innervation small diameter nociceptors
Sympathetic innervation
Proprioceptive innervation
Vascularization
Focus on Joint as an Organ
Slide6Required Element - Research Project Mapping of Neurons in Joint TissuesResearch project to map the sensory innervation of the joint tissues in animal models orhuman tissues or bothFocus on at least one of the high priority joint types KneeTemporomandibular Projects that study only one joint type
must include a plan to expand the proposed approach to a different joint type.
Applications that do not have a primary focus on temporomandibular or knee joints; and on the innervation of multiple tissues and structures within those joints, will be considered non-responsive.
Slide7Objectives and Approach Global understanding Types and distribution of neurons in joint tissues Innervation changes with age, sex, physical activity
Innervation changes with joint degeneration or arthritis
Approach - reporter constructs expressed in specific types of neurons, or similar tracer technologies available only in certain animal models
Translational understanding
Individual types of neurites present in order to
Identify key receptors and mediators that induce pain by activating specific sensory neurons
Approach - studying human tissues, or animal models that more closely approximate the anatomy and function of human joints
Slide8RequirementsAnimal modelsAssess changes in innervation based on sex, age, and physical activityAssess changes in innervation that occur with tissue degeneration/arthritisDiscuss how the findings and approaches can be extrapolated or applied to the study of human tissue and disease.Human TissueIdentify the types of nerves in the various components of the joint, whether healthy vs diseased tissue samplesCapture basic donor phenotypic information such as age, sex, race, disease severity, etc.
Slide9RE-JOIN Research Project DeliverablesMaps with the location of the afferent neurites of dorsal root ganglia (DRG) and trigeminal ganglia (TG) sensory neurons involved in joint pain.Phenotype of the neurons that supply the joint tissues and the attribution of those neurites to specific types of neurons in the DRG and TG.A description of changes in joint neuron with age and how these changes are influenced by sex, physical activity, etc.A description of changes in neurons accompanying degenerative and inflammatory changes in the joint.
An improved understanding of joint-specific vs. shared patterns of changes in innervation with age or disease in different joint types.
Validation of animal model maps in human tissue.
Preliminary evidence for target identification of new treatments for joint pain.Large, annotated datasets and metadata to be shared under FAIR and Open Science principles.
Slide10Optional Element – Technology Development or AdaptationGoal Improve the ability to map neurons in joint tissuesProjects solely focused on developing technologies for the study of animal models must include a discussion of how the technology could be adapted for use on human subjects or human tissue samplesAreas of interest include, but are not limited to:Technologies that can be extended to probe multiple joint types.Technologies that significantly advance the ability to assess sensory neurons in dorsal root ganglia (DRG) and trigeminal ganglia (TG) that extend to joint tissue.Technologies that significantly advance the ability to assess sensory neuron density, distribution and plasticity throughout the joint in humans at a larger scale or in vivo.Technologies that facilitate the identification of mediators that activate sensory neurons in situ and increase our understanding of how damage-associated molecules from different joint tissues activate pain neurons.
Slide11Data harmonization, integration and visualization Research Teams will work collaboratively with the Data Coordinating Group (funded separately) Integrate the data generated, to the extent possible, with common annotation and metadata.Develop methods to combine data from complementary techniques (e.g., optical images and omics) Data sharing and curation are expected to be significant amounts of work
Budget accordingly for these tasks
Research Teams should identify a staff member charged with curation (at least 30% effort)
Data will be shared amongst the Research Teams and, as rapidly as appropriate, with the public, through existing NIH portals (also funded separately).Research Teams are expected to collaborate and work with the integrated dataset compiled by the Data Coordinating Group to create maps or models or other means of visualizing the innervation of the tissue and structures of the joint (collaborative projects set aside).
Slide12Data Coordinating GroupData coordination will tentatively be provided by the NIH SPARC program’s Data & Resource CenterSPARC Data Coordination Core (PI: Joost Wagenaar, UPenn) – Software services to facilitate capturing, storing, and disseminating dataSPARC Knowledge Management Core (PI: Maryann Martone, UCSD) – Curation of all datasets to a common structure/standardCurated datasets are made available through a web portal:https://sparc.science
Slide13Visualization Curated datasets will be leveraged to create maps, models, or other means of visualizing the innervation of the structures and tissues of the jointMapping data into common coordinate spaces and knowledge models can enable integration, exploration, and visualization of anatomy and function
Slide14Cooperative Agreement Mechanism … Working Together as a Consortium“Assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the recipients is anticipated during the performance of the activities.The NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership roleThe dominant role and prime responsibility resides with the recipients for the project as a wholeThe work to be carried out under the award will be conducted collaboratively with other members of RE-JOIN and the NIHThe work of the Consortium will evolve to address the overall goals, gaps and opportunities that may be identified post-award and will be reviewed and approved by the Steering Committee.
Slide15Consortium-wide Administration Provide operational management and coordination of consortium-wide activities including but not limited to:Providing support to the chairs of the Steering and Executive Committees, and future working groups including planning and arranging meetings.Establishing and maintaining effective communications across the consortium to ensure the members understand their roles and responsibilities and are kept abreast of the scientific and procedural development in the program.
Coordinate development of and adherence to network-wide policies and procedures.
Track data and adherence to timelines.Assist with the planning and submission of manuscripts for publication.
Budget should include a line item for Consortium-wide administrative costs of $100,000 This line item would cover costs (including dedicated personnel)
These costs are distinct from management of individual award
Slide16Key DatesLetter of Intent – Due March 11, 2022Applications Due – April 11, 2022Council – August 2022Earliest Start Date – September 2022Number of Awards – 4-6Budget - Limited to $1.6M Direct Cost per yearThis must include $100,000 Direct Costs for Administration of the Consortium $250,000 Direct Costs for Consortium-wide Collaborative Projects in years 4 and 5
Should be reflective of scope
Slide17Research Plan (12 page limit) Specific Aims: Overall goals for the entire project.Research Strategy: 1. Background and Significance2. Activities and Management of the Research Team3. Preliminary Data4. Approach
Slide18Other AttachmentsOverall Project Timeline (Required – 1 page maximum):include a project timeline in the form of a Gantt chart or similar that includes all major tasks to be performed during the project. Include estimated start and completion dates for those tasks and identify the contributions expected from each PD/PI toward accomplishing each task.Technology Development Plan (Optional - 6 pages maximum):
Describe the goals, approach, how it will advance the research, data supporting the development or enhancement of the technology proposed, its applicability and translatability,
e.g., to humans and or to other joint types; and advantages.
Technology Development Plan Milestones and TimelineDescribe all interim objectives (research and/or developmental milestones) to be achieved during the course of the project.
Identify any impediments or dependencies that could require a revision in the work plan with a discussion of alternative approaches.
Discuss criteria by which each milestone achievement will be assessed.
Provide a timeline for the anticipated attainment of each milestone and the overall goal(s).
Slide19Review CriteriaSignificanceFor applications proposing animal models, is a meaningful path proposed to understand the relevance of the findings to human joint innervation in health and disease?For studies on human tissues, are the donor populations sufficiently phenotyped and relevant to understand innervation in normal and pathologic conditions?InvestigatorsDoes the team bring a diversity of expertise?Are staff identified who will be able to manage, curate and perform quality control on the data produced by the Team and harmonize and share that data with the Consortium?
Innovation
Does the strategy reflect consideration of the joint as an organ that includes several structures and tissues? Does the research proposed involve innovative combinations of approaches from different disciplines to address its goals?
Slide20Review Criteria – Approach Will the approach lead to a holistic understanding at a global level of the sensory innervation of the different tissues and structures that collectively form a joint, and whether these change with age, sex, physical activity or joint degenerationWill the approach provide knowledge about the specific types and distribution of neurites in different human joint tissues and structures that will enable the identification of key receptors and mediators that induce pain and thereby facilitate the development of new approaches to treating pain?If the application proposes to focus only one joint or only on animal models, is the path to extend the observations to other joints and/or human tissue discussed and scientifically sound and feasible? Does the approach include consideration of sex and age as biological variables?
If appropriate, will plans for technology development enhance the goals of the proposed projects or the broader overarching goal of RE-JOIN?
Slide21HEAL Expectations In addition to scientific diversity, applicants should strive to incorporate diversity in their team development plan. Research shows that diverse teams working together and capitalizing on innovative ideas and distinct perspectives outperform homogenous teams.NIH intends to maximize the impact of HEAL Initiative-supported projects through broad and rapid data sharing. See HEAL Initiative Public Access and Data Sharing Policy (https://heal.nih.gov/about/public-access-data)All applications are required to include a Data Management and Sharing Plan
Outline how scientific data and any accompanying metadata will be managed and shared
Describe data types, file formats, submission timelines, and standards used in collecting or processing the data. The NIH HEAL Initiative will require a high level of coordination and sharing among investigators. It is expected that NIH HEAL Initiative awardees will cooperate and coordinate their activities after awards are made and participate in HEAL Initiative meetings and other activities.
Slide22Restoring Joint Health and Function to Reduce Pain (RE-JOIN) ConsortiumUnderstanding changes in sensory neuron innervation of the “whole joint”, healthy and diseased.
Slide23Q&AErin Quinlan (NCCIH)Devon Oskvig (NIA)Kan Ma (NIAMS, review) Andrew Weitz (NIBIB)Melissa Ghim (NIDCR)Jules Bachman (NINDS)Michael Oshinsky (NINDS)Raise Hand
Chat to Everyone
Slide24Visit the RE-JOIN webpage for latest updatesRestoring Joint Health and Function to Reduce Pain (RE-JOIN) Consortium (https://www.niams.nih.gov/grants-funding/supported-scientific-programs/restoring-joint-health-and-function-reduce-pain-re)