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The American Heart Association / Allen Initiative in
Brain Health and Cognitive Impairment


Applications open in Grants@Heart: Monday, May 21, 2018

Application Deadline: Friday, July 6, 2018

*Applicants will be notified of second-phase proposal invitations by late August.


aha_asa_logoPaul G. Allen Frontiers Group Logo

The American Heart Association / American Stroke Association (AHA) and Paul G. Allen Frontiers Group have a mutual interest in brain health and healthy aging. We believe, and emerging research supports, that the current dichotomy between cerebrovascular diseases and neurodegenerative diseases, once considered mutually exclusive conditions, may impair a more effective approach to understanding and mitigating these disorders. Together with other contributors, we seek innovative proposals to disrupt the incremental trajectory of brain health research and open new frontiers of biomedical discovery to improve and lengthen lives.

Problem to Address

As health advances allow people to live longer, healthy aging is an urgent frontier for research. The burden of age-related cognitive impairment – whether from Alzheimer’s Disease, vascular dysfunction, the combination of these, or other causes – is growing exponentially. These debilitating diseases are costly, both to our health care system in terms of long-term care facilities, and to individuals and their families in terms of personal / emotional toll.

Through substantial investment in research to find causes and cures for Alzheimer’s Disease, the science community has revealed the late-stage manifestations of Alzheimer’s in the brain, for example through imaging and biochemical markers. However, we still lack a sufficiently precise and comprehensive understanding of both the underlying causes and the role of contributors. Only with this knowledge can adequate prevention, diagnosis and/or treatment be designed.

Meanwhile, neurologists and vascular scientists have made headway into understanding the broader field of vascular cognitive impairment, whether resulting from major and micro infarcts, white matter disease, cerebral small vessel diseases or other factors. These pathologies most often co-exist, and potentially interact with neurodegenerative processes and pathologies like Alzheimer’s Disease, either as epiphenomena, causal, or otherwise multi-directional interactive pathologies.

To create new bridges and collaborations in the scientific and medical community between neuroscientists concentrating on brain cells and vascular biologists on blood vessels, the AHA-Allen Initiative acknowledges a spectrum of potentially overlapping or interactive age-related disorders leading to cognitive impairment, including Alzheimer’s Disease, and seeks to uncover novel and shared contributing factors to better understand the mechanisms underlying these related diseases.

Scope

The purpose of this research initiative is to discover and fund highly-promising teams of investigators who will expand the frontiers of bioscience, pursuing creative, transformative ideas with the potential to move brain health and cognitive impairment science forward.

The AHA and Paul G. Allen Frontiers Group, with additional funding contributors including the Oskar Fischer Project, will grant a competitive basic science research award(s) of up to $43 million over eight years to one or more highly inspiring and innovative integrated team(s). New frontiers of discovery in brain health, and more specifically in cognitive impairment, will be opened when expertise and novel advances are shared and leveraged among basic and clinical cerebrovascular scientists and neuroscientists. Such integrative studies have the potential to bring truly novel directions of inquiry to the current incremental progress in the field of neurodegeneration and Alzheimer’s Disease research, with potentially exponential or transformational new insights.

Science Focus

The intent of the American Heart Association / Allen Brain Health and Cognitive Impairment award(s) is to fund large-scale integrated research that will identify novel, early, actionable, biological / mechanistic contributors to age-related cognitive impairment.

 

Science Focus
  
NovelEntirely new or previously undeveloped, unexploited, insufficiently understood
EarlyPrecursors to or initial stages of dysfunction, as opposed to late-stage evidence
ActionableAble to be mitigated or reversed
MechanisticFunctional properties and processes, what and how changes occur
Age-RelatedAssociated with aging, as opposed to purely genetic, pediatric, or other forms

Based on the latest available and emerging evidence, and the priorities of the contributing funders, the following topics are of particular interest, with illustrative examples:
 

  • The neurovascular unit (NVU) in relation to cognitive function
    • For example: endothelial dysfunction, capillary rarefaction, exosomes
  • Proteostasis in relation to cognitive function
    • For example: novel clearance pathways beyond intracellular protein trafficking (such as trans-vascular, peri-vascular, para-vascular)
  • Inflammation in vascular and neural systems in relation to aging / cognitive function
    • For example: role(s) of monocytes and lymphocytes
  • Role of astrocytes and microglia and their effects on cognitive function
    • For example: clearance of metabolic products and neural network signaling
  • DNA repair and epigenetic aging mechanisms in vascular and neural systems.

Applicants are expected to assemble an integrative team that will leverage diverse skills and perspectives to address a compelling selection or combination of the above or equally compelling relevant topics. Because early stage and causal mechanisms are of priority interest, studies focused exclusively on late-stage manifestations (such as the Alzheimer’s Disease pathology of amyloid plaques and neurofibrillary tangles) or non-modifiable / non-actionable biomarkers, for example, will be less competitive. Likewise, with a focus on novel discoveries of basic scientific mechanisms at play, large scale randomized trials and population studies will only be competitive if appropriately linked to the mechanistic discoveries. Fellowships and training within the projects are welcome.

Target/Eligibility

Team lead applicants are expected to demonstrate the following attributes:

  • Ph.D. and/or M.D. (or the equivalent).
  • Faculty appointment at an eligible nonprofit institution in the U.S. or equivalent faculty position at a foreign University that meets foreign equivalency determinants for a non-profit in the United States.
    • U.S. Federal government employees are not eligible.
  • Ability to develop new tools and methods that support creative experimental approaches to questions, utilizing techniques from other disciplines, if appropriate.
  • Creativity in their scientific ideas and commitment to take risks on forward-looking concepts of major scientific impact.

We seek and strongly encourage applications from women and members of minority groups that are under-represented in biomedical sciences.

Awardees will be invited to and expected to attend symposia, conferences and other gatherings of American Heart Association and/or Paul G. Allen Frontiers Group researchers. These events offer time for cross-fertilization of frontier bioscience ideas and new collaborative opportunities.

Application Submission

The application requires the following three documents:

A. Research Proposal - (5 pages, 12 point Arial font, 1 inch margins on all four edges) Please address all of the following points:
 

  1. Concept: your creative idea or hypothesis related to early mechanistic contributors to cognitive impairment. Include:
    • How your plan advances research into new frontiers and/or difficult problems not previously explored.
  2. Plan: your research plan to produce compelling new knowledge prioritized in this call for proposals. Include:
    • A timeline of key milestones you would target in the 8-year study duration.
    • An estimated total budget requirement and brief rationale, including number and role of paid positions and/or approximate allocation between institutions within the team.
  3. Team: who will be on your team and why you selected them. Include:
    • Your (team’s) capacity to develop new tools and methods that support creative experimental approaches to questions, encompassing concepts or techniques from other disciplines.
    • The lead applicant / institution’s capacity to receive and manage research awards of the scale and duration available.
Note: The Grants@Heart online application will require a lay summary of no more than two paragraphs that can be understood by a non-scientist reviewer:
    • What is the major problem being addressed by this study?
    • What specific questions are you asking and how will you attempt to answer them?
    • Overall, what is the potential impact of this work to the field of brain health and cognitive impairment?

B. Biosketch (for PI and any co-PIs; up to 5 pages each)

C. A list of up to 20 relevant or important publications (1 page)

Award Amount & Duration

  • Awards are for an eight-year period.
  • Amount: first stage applicants should propose a scope of research that could be completed at a minimum level of $15M or larger. Selection Committee will determine finalists and provide budget guidance for invited second stage submissions.
  • Award budget can cover costs such as PI and any co-PI salary/fringe; salaries/fringe of lab personnel; other expenses such as laboratory supplies; equipment; animal costs; human subject recruitment/reimbursement; travel; publication costs. Up to 10% may be used for institutional indirect costs. A full budget will be requested only from invited second-stage proposals.

Peer Review Criteria

Impact:
Is the research described by the candidate likely to lead to the development of significant contributions in the neurodegeneration science areas outlined in the RFA? Does the research challenge existing paradigms or critical barriers to progress in the field? Does the candidate propose transformative approaches to major research challenges in neurodegeneration?

Investigator(s):
Does the candidate and/or team express creative ideas and a commitment to pursue pioneering work at the frontiers? Does his/her/their record of accomplishment and scientific choices suggest the ability to transform the field and leverage different domains of science and expertise?

Innovation:
Are there new conceptual innovations in the proposed project? Does the applicant describe the development of new tools and methods that support creative experimental approaches to questions, encompassing concepts or techniques from other disciplines?

Collaboration:
Does the candidate provide demonstrated evidence of the proposed team’s ability and commitment to collaborate effectively, particularly as it relates to integrated strategies of the proposed topics of study? Does the candidate and/or team have a strong history and track record of collaborating with other experts in the field?

Synergy:
Does the proposal provide a clear vision of scientific direction, with a compelling selection or combination of topics that complements and contributes to an integrating theme? Will the combined effect be greater than the sum of its parts?

Review Process

The first stage of review will evaluate the written proposal against the peer review criteria listed above.

A second stage proposal will be invited from only the highest ranked candidates and will include a more detailed narrative, research plan, and an interview process. Detailed requirements for the proposal and interview will be communicated when finalists are notified of their advancement. Finalists should anticipate submission of a 15-page research plan and detailed budget and additional information associated with a proposal of this type, including, for example: a description of the research environment(s), assurance(s) related to ethical use of animal and/or human subjects and tissues, a data sharing plan, etc.

Applicants are prohibited from discussing proposals with peer reviewers. This is a form of scientific misconduct and will result in removal of the application from funding consideration and institutional notification of misconduct.

Relevant Policies:

Public Access: The AHA requires that all journal articles resulting from AHA funding be made freely available in PubMed Central within twelve (12) months of publication. It will be the responsibility of the author to ensure this occurs.

Open Data: Any research data that is needed for independent verification of research results must be made freely and publicly available in an AHA-approved repository within twelve (12) months of the end of the funding period (and any no-cost extension).

For more information on the above polices, see AHA's Open Science Policy webpage.

Timeline

Timeline
  
May 10, 2018Program announcement and funding opportunity published
July 6, 2018First phase application submission deadline
August 17, 2018Notification of second stage proposal invitations
Target: September 2018(invited) Second phase proposal deadline
Target: October 2018(invited) Finalist interviews
Target: November 2018Announcement of award(s)