Catalyst Grants: (a) Inventions – Tools, Techniques and Devices Grants; and (b) High-Risk, High-Benefit Grants (December 2008) : RMNI Eligible Research AreasBackground
The fundamental goal of the Regenerative Medicine and Nanomedicine Initiative (RMNI) is the development of meaningful multi-disciplinary research approaches to regenerative medicine and nanomedicine. This goal is consistent with the Integration theme of the Institute of Genetics, namely to fuel the convergence of the modern life sciences (genetics, biochemistry, molecular and cell biology) with the physical (chemistry and physics), mathematical and applied (engineering and computer) sciences. These approaches also need to balance consideration of the social, cultural and ethical impacts of these novel technologies with key rehabilitation and accessibility issues, as well as the potential economic costs of such treatments. Research into the maintenance of health or prevention of disease and degeneration is also encompassed by this initiative.
Objectives and Relevant Research Areas
Specific objectives and relevant areas of research for this strategic initiative are described under the general thematic headings of Nanotechnology Applied to Health (Nanomedicine), Stem Cells, Tissue Engineering, and Rehabilitation Sciences. Please note that there is considerable overlap between these areas. Applicants are not required to address multiple thematic areas in their application, although a commitment to multi-disciplinary research is critical. Applicants are encouraged to clearly explain how their application addresses at least one of the themes outlined below.
1. Nanotechnology Applied to Health - Nanomedicine
Many definitions of nanotechnology are possible. These definitions typically encompass a wide range of technologies that measure, manipulate, or incorporate materials and/or features with at least one dimension between approximately 1 and 100 nanometers (see for example ASTM International Terminology for Nanotechnology E2456-06). Such applications typically exploit the properties, distinct from bulk/macroscopic systems, of nanoscale components.
At present, CIHR broadly defines nanomedicine as the specialized measurement or intervention - at a molecular scale - needed to treat disease or restore function.
This definition is meant to be inclusive of techniques and methodologies relevant to health research that do not necessarily fit within the more narrow definitions of nanotechnology. Relevant disciplines could include, but are not limited to, mathematics, computational sciences, chemistry, physics, and engineering and applied sciences. Potential general applications of nanomedicine could include, but are not limited to:
- Novel approaches to functional molecular-scale imaging, including devices, compounds, integrated techniques and correlated approaches;
- Novel drug delivery approaches, devices, materials, including delivery across the blood-brain barrier;
- Novel approaches to the synthesis, design, implementation, and characterization of biomolecular arrays (small molecule, peptide, protein, biomolecule, antibody) for high-throughput, multiplex screening;
- Integration of nanostructured materials, devices, sensors with microfluidic systems for identifying, measuring, and mapping biomolecular interactions;
- Development and application of novel physical, chemical, or electronic probes, tools, and techniques to the determination of single molecule (peptide, protein, biomolecular complex) structure-function relationships;
- Novel approaches for the rapid in situ determination of single molecule structure, dynamics and reactivity;
- Characterization of the genetic, molecular and signaling pathways associated with physiological integrity, disease, injury, loss of function, and cell or tissue senescence;
- Definition of important gene-environment interactions in determining health and new potential therapeutic targets for diseases and conditions;
- Novel approaches (computational and experimental) to understanding the development of the structural and functional hierarchy present in complex biomolecular systems;
- Ethical, environmental, legal, cultural, and social consequences of nanomedicine, as well as the potential economic costs of such treatments (see Section 1A for more detail);
- Health impacts of nanotechnology, including research to meet health policy or regulatory aims (see Section 1A for more detail);
Note: Applicants planning to work with nanoparticles (i.e. particles with lengths in two or three dimensions that are smaller than 100 nm) are required to explicitly address the potential health safety and environmental risks in their research proposals. Proposals focused on nanoparticles are encouraged to include toxicological expertise on their teams.
Specific applications of Nanomedicine that may be directly supported by initiative partners include, but are not limited to:
1.A. The Health Impacts of Nanotechnology
The potential benefits of nanotechnology applied to health are great, due in part to the unique properties of matter at this scale length. However, these very properties also make the health safety and environmental risk assessment of some nanotechnology-based materials difficult - particularly for nanoparticles, where toxicity compared to their bulk counterparts is often poorly understood. Specific concerns for nanoparticles include a higher chemical reactivity (due to smaller particle size, different crystal shapes/lattice arrangements, etc.) and different reactivity to light (due to quantum confinement).
In collaboration with other funding agencies and departments of the Canadian Government, CIHR recently supported a Canadian Workshop on Multidisciplinary Research on Nanotechnology: Gaps, Opportunities and Priorities. This workshop identified key gaps and research needs in nanotechnology, particularly as they relate to NE3LS issues (i.e. nanotechnology ethical, environmental, economic, legal and social issues), environmental and health impacts and risks, and the regulatory mechanisms needed to address them.
Based on the research priorities identified in this workshop, RMNI and its funding partners will provide research funding support through this funding opportunity (subject to availability of funds) in the following areas of nanotechnology research:
- Ethics and Related Domains
- Policy, Regulatory Development and Governance
- Science Environmental and Health Risks
- Social Science and Humanities Perspectives
For information on specific eligible research topics identified at this workshop, please see the Summary of Key Research Gaps.
1.B. Novel Drug Delivery Approaches, including Gene Therapy and Vaccines
In the context of this initiative, novel Nanomedicine drug delivery approaches could include any drug delivery technology where a critical component of the drug delivery system has at least one dimension between approximately 1 and 100 nanometers, and where specific activity at this scale length is critical for function. This definition includes gene therapy, which can be broadly defined as any approach that corrects gene expression responsible for disease development. Specific therapeutic applications of Nanomedicine include, but are not limited to:
- Use of carbon nanostructures (e.g. carbon nanotubes, fullerenes, etc.) for therapeutic drug delivery
- Use of dendrimers and aptamers for therapeutic drug delivery
- Development of novel liposomal drug delivery systems, where a critical component of the liposome is in the low nanometer range
- Development of novel vaccines using nanomedicine approaches
- Identification of therapeutic genes and development of novel gene delivery systems (i.e. vectors);
- Optimization of appropriate vectors for specific cell types, including stem and progenitor cells and their use in bioengineered scaffolds and implants;
- Development of safe and effective strategies for delivering and integrating therapeutic genes to different organs and tissues, including across the blood-brain barrier;
- Characterization of immune system responses to vectors and transgene products using existing or novel imaging technologies;
- Exploration of the socio-economic, ethical, legal, and cultural aspects of clinical applications of nanomedicine therapy for human diseases and for influencing life-course changes in tissues, systems and functions.
Of particular relevance to this strategic initiative is the development of novel drug and gene delivery systems based on nanomedicine principles, including the application of novel imaging technologies to monitor effectiveness and determine potential adverse effects. The integration of drug and gene therapy with stem/progenitor cell research and tissue engineering approaches to regenerative medicine is also encouraged.
1.B.i. Blood Brain Barrier (BBB)
Several initiative partners are interested in supporting applications using drug delivery across the blood-brain barrier (BBB). Blood vessels in the brain are unique in having specialized physiological and biochemical systems that control the movement of molecules and immune cells into and out of the brain. These aspects of the BBB are poorly understood and determining their nature would have tremendous importance for both the understanding of neuropsychiatric diseases and for the delivery of treatments for many brain disorders. Novel applications of nanomedicine could include vaccine approaches against various forms of addiction or vaccines against neurodegenerative diseases, for example.
2. Stem Cells
Stem cells are an area of considerable research excellence in Canada, and form an integral component of this initiative in Regenerative Medicine and Nanomedicine. Eligible areas of research include pluripotent embryonic stem cells and post-natal "adult" stem cells. Researchers are encouraged to consider approaches to integrate stem cell research with tissue engineering and rehabilitation sciences, as well the application of nanomedicine technologies to stem cell research.
Researchers should consult with the Updated Guidelines for Human Pluripotent Stem Cell Research when preparing their applications. All applications that propose research falling within the scope of the Guidelines will be subject to review by the CIHR Stem Cell Oversight Committee.
Relevant research areas on therapeutic applications of stem cells include, but are not limited to:
- Signaling pathways responsible for the differentiation and replication of cells, and their role in the repair of diseased/damaged cells and in the regeneration of healthy cells and tissues later in life (i.e. senescence versus quiescence);
- Stem/progenitor cell molecular biology and the use of stem/progenitor cells in regenerative medicine and tissue repair and replacement;
- Molecular and signaling pathways associated with regulation of the differentiation and replication of stem and progenitor cells and their role in the repair of diseased/damaged cells, and the regeneration of healthy cells and tissues;
- Innovative applications of stem cells to tissue repair and regeneration;
- Evaluation of stem cells in animal models of human disorders;
- Ethical, legal, social, cultural and economic consequences of stem cell-based approaches to tissue repair and replacement.
3. Tissue Engineering
One of the key goals of regenerative medicine is to stimulate the renewal of bodily tissues or the restoration of function through the use of natural or bioengineered materials. Tissue engineering is thus an integral part of regenerative medicine, and Canada is recognized for its expertise in several areas, including research excellence in several key organ systems as well as the basic sciences of biomaterials, scaffolding and drug delivery for both soft and hard tissue applications.
Specific therapeutic applications of tissue engineering research include, but are not limited to:
- Novel cell delivery models and approaches, including delivery of cells in scaffolds to promote healing for repair, replacement or regeneration of tissues;
- Development of scaffolds with appropriate characteristics to promote cell and tissue survival and integration;
- Development of novel animal and culture models for regenerative medicine applications, including innovative models of acute and chronic injury, aging models, organ cultures and co-culture systems;
- Molecular and biochemical basis of vascularization and angiogenesis in native and exogenously transplanted tissues and organs;
- Approaches to minimize cell death and promote cell survival and differentiation in transplants;
- Application of tissue-engineered biomaterials as conduits or shunts in tissue regeneration;
- Development of important new insights into "normal" structure, function and/or development of tissue and organ systems of interest;
- Development of effective new strategies for improving healing, repair, biological replacement or regeneration of tissue and organ systems of interest;
- Ethical, legal, social, cultural and economic consequences of regenerative medicine based on tissue engineering strategies.
4. Rehabilitation Sciences
This initiative in Regenerative Medicine and Nanomedicine is also interested in funding innovative research in rehabilitation. Advances in neurosciences, physiology, motor learning and brain imaging techniques have challenged the traditional view of regeneration as it applies to rehabilitation. The broader concept of functional restoration is proposed to embrace the continuum of restorative processes or plasticity induced by rehabilitation interventions that occur in the brain, spinal cord, peripheral nerves and muscles to promote recovery of function after stroke, injury or disease, or to limit the effects of aging.
Specific therapeutic applications of rehabilitation research to regenerative medicine include, but are not limited to:
- Understanding skill-dependent cortical plasticity at the level of biochemical and molecular events using novel nanomedicine and technological developments;
- Development of research programs that bridge basic animal and human studies, leading to the development of improved rehabilitation interventions;
- Understanding how muscle responds at the molecular level to different types of exercise (e.g. strength, endurance, sprint), and what effects exercise may have in reversing or preventing immobilization-induced skeletal muscle atrophy, as an aid to devising guidelines for therapy;
- Examining whether there are gender- or age-based differences in skeletal muscle adaptation to exercise, and what effects pharmacological treatments may have on this process (e.g. corticosteroids, angiotensin receptor blockers (ARBs), statins, etc.);
- Characterization of factors regulating restoration of motor patterns after spinal cord injury (SCI) in humans, and determination of stimulation parameters to promote appropriate long-term re-expression;
- Effects of activity-based intervention approaches on reversal of pathological muscle fiber type changes after SCI;
- Understanding alterations in intrinsic neuroplasticity, at cortical or segmental levels, following traumatic CNS injury, and the effects of pharmacological or physical therapies on unmasking or reactivating latent innervation;
- Understanding the molecular and biochemical basis of muscular dystrophy and myopathies, and what types of exercises or interventions are effective and why (e.g. is there a "threshold" where adaptive stressors can induce physiological adaptation, beyond which an exacerbation of the pathology occurs?);
- Determination of secondary biological changes in hemiparetic muscle that may effect performance capacity, metabolic characteristics and stroke risk factor profiles;
- Effects of stem cells, tissue engineering, or gene therapy on restoration of function following CNS injury, stroke or degenerative brain disease, when delivered alone or in combination with physical therapy;
- Development of interventional models that are most effective in improving motor function following CNS injury, stroke (e.g. role of task-oriented exercise) or onset of degenerative brain disease;
- Evaluation of rehabilitation techniques and delivery of rehabilitation services to aboriginal populations;
- Evaluation of rehabilitation techniques on functional recovery, cortical re-organization, muscle adaptation, social re-integration and quality of life issues.
Some of the broader research questions that could be addressed in proposals submitted to this initiative include, but are not limited to:
- Key issues surrounding the time course of recovery: i.e. when should rehabilitation be started, what intensity and duration of therapy should be provided; and is there a therapy "window of opportunity", etc.?
- How to promote the maintenance of gains over time?
- Should restorative therapy be provided to persons with all levels of impairment (mild, moderate, severe)?
For questions about this initiative and research objectives contact:
Eric Marcotte, Ph.D.
Regenerative Medicine and Nanomedicine
Canadian Institutes of Health Research