RMNI Eligible Research Areas (July 2009)

Background

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.

The commitment to supporting truly innovative and leading edge multi-disciplinary research directed against key health research problems makes up the core of this strategic 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 explicitly address large scientific questions or health research problems in their proposed research projects.

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 continues to broadly define 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, and sensors with microfluidic or other systems for identifying, measuring, and mapping biomolecular interactions
• Development and application of novel physical, chemical, optical 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 two or more characteristic dimensions that are less 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.

In addition, the Canadian Space Agency (CSA) will consider funding Emerging Team grants for proposals relevant to its strategic interests in life sciences, namely diagnostics and bio-sensors. To meet the challenges of conducting science in space, the development of biomolecular arrays, bio-sensors, in situ biomolecular measures and associated hardware for use in neuroscience, bone and muscle loss and cell biology is critical. (Updated: 2009-10-02)

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). Potential applications of the health impacts of nanotechnology could include, but are not limited to:

• Design of multifunctional systems at the nanoscale (e.g., multi-modality imaging or therapy and combination system)
• Better fundamental understanding of the interactions of nanoscale particles, and structures with biological systems
• Strategies to improve the rational design of nanostructures for in vivo applications
• Analytical technologies for high-throughput screening of nanotoxicity
• Clinical validation and evaluation of nanotechnology
• The impact of nanostructure design on biological response

Further, in collaboration with other funding agencies and departments of the Canadian Government, CIHR 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.

For information on additional eligible research topics identified through this workshop, please see the Summary of Key Research Gaps on the RMNI website. 

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 functionality is critically dependent on, or uniquely defined by, this length scale. 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.), dendrimers, aptamers, and liposomes for therapeutic drug delivery
• Development of novel vaccines using nanomedicine approaches, including against various forms of addiction or vaccines against neurodegenerative diseases
• 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.

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. In this context, stem cell research refers to the derivation and/or study of human and/or animal stem cells of a pluripotent nature from all potential sources, including embryonic and somatic tissues. 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 and epigenetic mechanisms 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, including the use of nanomedicine approaches
• 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

The Canadian Space Agency (CSA) will support high quality research leading to tissue engineering in microgravity.  Space offers several advantages over the Earth environment for tissue engineering.  The CSA will consider funding Emerging Team grants for proposals deemed relevant to its strategic interests.  In order to encourage innovative and diversified ideas, proposals in the area of tissue engineering in space will not otherwise be restricted to specific areas of research.  Please see Description of Partners for more information about the Canadian Space Agency. (Updated: 2009-10-02)

4. Rehabilitation Sciences

The 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 musculoskeletal system 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 and/or age-related 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
• 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)

Contact Information

For questions about this initiative and research objectives contact:

Eric Marcotte, Ph.D.
Associate Director
Regenerative Medicine and Nanomedicine
Canadian Institutes of Health Research
Tel: 905-467-1822
Fax: 613-954-1800
E-mail: eric.marcotte@cihr-irsc.gc.ca

For questions on CIHR funding guidelines, how to apply, and the peer review process contact:

Kelly Fitzpatrick
Team Lead
Knowledge Creation Programs
Canadian Institutes of Health Research
Tel: 613-941-4640
Fax: 613-954-1800
E-mail: kelly.fitzpatrick@cihr-irsc.gc.ca

Description of Partners/Collaborators: CIHR Institutes and External Organizations

Note: Additional partners, including partners from government, industry and the private sector, may join this funding initiative over the coming year.

Canadian Institutes of Health Research (CIHR)

CIHR is the Government of Canada's agency for health research. CIHR's mission is to create new scientific knowledge and to enable its translation into improved health, more effective health services and products, and a strengthened Canadian health-care system. Composed of 13 Institutes, CIHR provides leadership and support to nearly 12,000 health researchers and trainees across Canada.

The Regenerative Medicine and Nanomedicine Initiative (RMNI)

The Regenerative Medicine and Nanomedicine Initiative (RMNI) provides funds for multi-disciplinary and integrative research in new and emerging areas that span the mandate of CIHR, including nanomedicine and regenerative medicine. Supported research fields include nanotechnology applied to health (nanomedicine), stem cells, tissue engineering, rehabilitation sciences, and related social, ethical, environmental, economic, and legal issues. The goals of the initiative include the regeneration and repair of injured tissues and organs, the development of specialized tools and interventions needed to treat diseases and restore function, and the maintenance of health and the prevention of disease. Co-led by the CIHR Institutes of the Institute of Neurosciences, Mental Health and Addiction (INMHA) and the Institute of Genetics (IG), RMNI is an integrative model of collaboration between funding agencies, government departments, NGOs and industry.

CIHR - Institute of Aging

IA supports research to promote healthy aging and to address causes, prevention, screening, diagnosis, treatment, support systems, and palliation for a wide range of conditions associated with aging. IA has identified five priority research areas for research on aging and health , which will be considered within this initiative (in no particular order): Healthy and successful aging; Biological mechanisms of aging; Cognitive impairment in aging; Aging and maintenance of functional autonomy; and health services and policy relating to older people. The Regenerative Medicine and Nanomedicine Initiative (RMNI) aligns strongly with CIHR IA's Mobility in Aging Initiative and the identified research and knowledge translation gaps: 

• Understanding and defining mobility in aging: trajectory of mobility status in health and disease, and from function to impairment
• Maintaining and restoring mobility in aging: impact of behavior, prevention, intervention and health system models
• Measures, tools, and technologies in research, assessment and mobility aids
• Maintenance of functional autonomy, and health services and policy relating to older people

CIHR - Institute of Circulatory and Respiratory Health

ICRH supports research into the causes, mechanisms, prevention, screening, diagnosis, treatment, support systems, and palliation for a wide range of conditions associated with the heart, lung, brain (stroke), blood, blood vessels, critical and intensive care, and sleep. The ICRH vision is to achieve international leadership by fostering an environment of openness, excitement, energy, commitment and excellence in highly ethical, partnered initiatives focused on research, research training, and research translation for the circulatory and respiratory sciences and for the betterment of the health of Canadians. In March 2007, following consultations with the ICRH community and Institute Advisory Board, the following eight priorities were identified:

1. Obesity, Diabetes and Cardiovascular Complications
2. Technology for diagnostic and therapeutic advances, including imaging technologies for early detection of disease
3. Psychological, social, behavioral and environmental determinants of at risk behaviour for chronic disease, and means of effective interventions
4. Sleep: circadian impact on respiratory and cardiovascular diseases, metabolism and obesity, and means of diagnosis, treatment and prevention
5. Biomarkers for chronic disease, including genetic, proteomic and phenotypic markers for prevention, diagnosis and guidance for therapy
6. Aging and the cardiorespiratory system: changing epidemiology, physiology and means to healthy aging and disease prevention
7. Injury repair and inflammation: mechanisms leading to the development of chronic diseases and their potential prevention
8. Transplantation-regeneration-cell based therapies to effect cure rather than palliation, including relevant bioethics aspect

The ICRH will consider providing financial support to highly ranked ICRH-relevant projects, depending on availability of funds.

CIHR - Institute of Genetics

The mission of the Institute of Genetics (IG) is to support excellent research on the genetic and biochemical basis of health and disease, including the interaction of genes with the physical and social environments, to facilitate the translation of research findings into health policy and practice, and to examine the ethical, legal and social implications of genetic discoveries. The IG encourages translational research by fostering collaboration between the basic and clinical research communities, and collaborates with other Institutes of CIHR to optimize the impact of genetic discovery on other disciplines. A critical responsibility of the IG is to examine the ethical, legal and social implications of new genetic discoveries.

CIHR - Institute of Infection and Immunity

The Institute of Infection and Immunity (III) seeks to establish national leadership, priorities and programs that promote innovative research to reduce the global burden of infection and immune-based disease and improve quality of life. The III supports research to enhance immune-mediated health and to reduce the burden of infectious disease, immune-mediated disease, and allergy through prevention strategies, screening, diagnosis, treatment, support systems, and palliation. The III has identified a need to support the development of new tools, technologies and methods capable of providing non-invasive evaluation of infectious and immune processes in vivo.

CIHR - Institute of Musculoskeletal Health and Arthritis

The Institute of Musculoskeletal Health and Arthritis (IMHA) will support research to enhance active living, mobility and movement, and oral health; and to address causes, prevention, screening, diagnosis, treatment, support systems, and palliation for a wide range of conditions related to bones, joints, muscles, connective tissue, skin and teeth. The mission of IMHA is to eradicate pain, suffering and disability, in order to enhance quality of life for people affected by arthritis, and musculoskeletal, oral and skin conditions. Applications will be considered in IMHA's six focus areas: arthritis, bone, oral health, muscle, MSK rehabilitation, and skin and must be linked to one of its three research priorities:

• Physical Activity, Mobility and Health
• Tissue Injury, Repair and Replacement
• Pain, Disability and Chronic Diseases

CIHR – Institute of Neurosciences, Mental Health and Addiction

The vision of the Institute of Neurosciences, Mental Health and Addiction (INMHA) is that innovative research will provide new knowledge of the biological and socio-cultural processes underlying neurological, mental and addictive disorders. As such, the INMHA's mission is to foster excellence in innovative, ethically responsible research in Canada that aims to increase our knowledge of the functioning and disorders of the brain and the mind, the spinal cord, the sensory and motor systems, as well as mental health, mental illness and all forms of addiction. The INMHA intends to support initiatives that mobilize and link scientists in innovative collaborative programs across these research domains. The INMHA seeks to translate this new knowledge into a better quality of life for all Canadians through improved outcomes, health promotion and health care services.

Canadian Space Agency

The primary objectives of the Space Life Sciences Program of the Canadian Space Agency (CSA) are to explore basic principles of biology to understand the role of gravity in life processes, to better understand how life functions and adapts to the environment of space and readapts upon return to the conditions on Earth, and to obtain knowledge and develop technology to produce safer space travel and improve life on Earth. Particular areas of interest include bone and muscle loss, adaptation of heart and other body systems and organs to weightlessness, maturation of organisms in space, biological effects of space radiation, and space psychology.
 
Space life science is essential in the preparation for the exploration of space. Long duration flight will become commonplace in future inter-planetary exploration, and understanding the biological consequences of microgravity and radiation exposure may be essential to survival. As more becomes known of these factors, countermeasures and pre-adaptations can be developed. Significant benefits to the quality of life and contributions to human welfare on Earth can be expected from the enhanced knowledge and new medical technologies resulting from the program. (Updated: 2009-10-02)