NIH – Engineering Next-Generation Human Nervous System Microphysiological Systems (R01, R21)

August 15, 2016 by School of Medicine Webmaster

The description below was taken from the R01 version of this FOA.  Also, note specific interests of  Institutes/Centers.

The purpose of this funding opportunity announcement is to stimulate basic research to develop next-generation human cell-derived microphysiological systems (MPS) with improved fidelity to complex human brain, spinal, peripheral nervous system and/or sensory end organ circuit physiology in vivo, which will ultimately facilitate analysis of higher order functional deficits relevant to complex nervous system disorders. This FOA is distinct from those focusing on optimization and scalability of assays for compound screening, although projects could in principle have utility for late stage evaluation of drug efficacy and toxicity. These MPS will have a multi-lineage, complex architecture representing the normal characteristics and functions of the relevant nervous system structure (e.g., sensory input systems, brain or spinal integrative systems, motor output systems) and will substantially exceed the state of the art in cellular maturation and integration, allowing reproducible measurement of circuit-level activity under physiological conditions over a long culture period.

The applications should define the current state of MPS technology as a benchmark against which the new MPS assay(s) will be developed and measured. Example approaches include, but are not limited to:

  • Utilization of novel materials, substrates or synthesis technologies (e.g., 3D printing, bioreactors, microfluidic platforms) to promote physiologically relevant tissue organization and/or maturation.
  • Integration of cell types consistent with physiologically relevant nervous system anatomy (e.g., excitatory, inhibitory & modulatory neurons, astrocytes, oligodendrocytes, microglia, pericytes, endothelial cells) into functional units that may include multipartite synapses, vascularization-perfusion, blood-brain barrier, glymphatic system and/or cerebrospinal fluid flow.
  • Novel strategies to reproduce physiologically relevant regional cellular organization (e.g., dorsoventral, rostrocaudal, laminar, columnar or nuclei structure), with both short- and long-range anatomical connectivity (e.g., local inhibitory-excitatory and/or modulatory connections, projections to distant lamina or nuclei).
  • Novel strategies to promote maturation of metabolic, signaling or synaptic activity in MPS.
  • Development of MPS with complex functional features potentially relevant to complex nervous system disorders (e.g., intrinsic and emergent network properties of cell assemblies, neural oscillatory activity, activity-dependent plasticity).
  • Inclusion of conditional or intersectional strategies that allow temporally and/or spatially cell-selective monitoring or manipulation of gene expression/function or of live cell activity and function.
  • Inclusion of innovative approaches to distinguish or deconvolute heterogeneous cell phenotypes from these model systems (e.g., multi-parameter single cell analysis), including those that are minimally perturbing.
  • Evaluation of how data obtained from MPS compares with human anatomical, histological or systems-level data, or data from other physiologically relevant paradigms, to facilitate MPS validation. Investigators are encouraged to explore the tools being developed under the NIH BRAIN Initiative, which if utilized, could further the development of human brain cell-derived MPS.

Examples of applications that do not fit the research objectives for this announcement include:

  • Developing tissues for transplantation.
  • Developing MPS from non-human tissues.
  • Utilization of simple 3D systems that do not significantly advance the state of the art to address disease-relevant questions.
  • A central focus on scaling assays or adapting for use in compound screening.

Deadlines:  Standard dates and standard AIDS dates apply


Filed Under: Funding Opportunities