This document provides highlights from RFAGM-05-006. For further information see the April 30, 2004 issue of the NIH Guide to Grants and Contracts or go to http://grants1.nih.gov/grants/guide/rfa-files/RFA-GM-05-006.html
PURPOSE OF THIS RFA
The purpose of this RFA is to solicit proposals for a Short Course(s) in Integrative and Organ Systems Pharmacology. The National Institute of General Medical Sciences (NIGMS) recognizes the importance of studies using intact organ system and in vivo animal models in the conduct of research. There is a growing need for functional analysis of biological systems to connect results at molecular and cellular levels to the expression of genetic and environmental determinants in the whole organism. This RFA solicits proposals for Education Projects that will introduce students to the knowledge and skills needed for studies of integrative organ system and whole organism biological responses to drugs and other physiological perturbations. The project should develop an appropriate, innovative curriculum to teach basic concepts and experimental techniques during a brief, but intensive short course, to be offered during the summer. Inclusion of independently funded follow-up experiences at either the home institution or through industrial internships is encouraged. Interested students will likely be drawn from graduate programs in pharmacology, physiology, toxicology, and related disciplines. However, the course should be open to participation of other students at advanced levels of training and career stages, and to students from industry and government as well as from academia. The training should foster their ability to assume leadership roles in all three sectors. The goal of these Education Projects will be to strengthen the research personnel base in the United States by broadening the exposure of students to training in integrative and organ systems sciences.
RESEARCH OBJECTIVES
Background:
The definition of Integrative and Organ Systems Pharmacology for the purpose of this RFA is as follows: "Pharmacological research using in vivo animal models or substantially intact organ systems that are able to display the integrated responses characteristic of the living organism that result from complex interactions between molecules, cells, and tissues."
Such studies are important because isolated molecules and cells in vitro do not accurately display all of the properties that they possess in vivo. Isolated molecules and cells do not adequately reflect the function of intact tissues, organs, and organ systems. Normal physiology, pathology, and pharmacology reflect not only interactions between molecules and cells, but interactions of multiple tissues, organs, and organ systems as well.
Concerns have been raised by academic and industrial scientists about the training of current students in the area of integrative and organ systems sciences. Most graduate students in the basic biomedical sciences receive limited training in physiology and integrative pharmacology. Even within the discipline of pharmacology, not all students gain sufficient hands-on experience with in vivo animal models and organ systems. Graduates need to have sufficient understanding of how to choose and use models that appropriately reflect the human condition under study. Furthermore, students need the skills to communicate with other scientists across the breadth of science from isolated molecule to whole animal and human clinical research that is required for translation of research results into health benefits.
Several factors suggest an increasing need for students trained in integrative and organ systems sciences. Bioinformatics and genomic approaches are suggesting new targets for study. Hypotheses generated by in vitro studies or by computational biology and systems approaches to the integrative behavior of living systems need to be tested in the actual living organism. The ability to develop genetically modified organisms has outstripped the ability to characterize the phenotypic changes in these organisms. Interest is growing in behavioral and neurobiological phenomena that can only be studied in relatively intact systems and living organisms. Discoveries in the areas of chemistry, genomics, and pharmacogenetics have accelerated the rate of research and have increased the demand for integrative and organ systems pharmacologists in the pharmaceutical industry. Pharmacologists, experienced with in vivo models, form an integral part of every drug discovery and development project and are essential to assuring that only safe and efficacious lead compounds go forward to clinical trials. New tools, such as microdialysis and imaging methods, have become available that enhance the collection efficiency and value of pharmacological data obtained in vivo.
Academic infrastructure at many institutions may not be able to meet the demand for appropriate training in this area. The success of reductionist approaches based on molecular and cellular methods has resulted in the displacement of many of the researchers formerly engaged in integrative and organ systems studies. The cost of animal subjects research has increased and the use of animal subjects in basic medical and graduate instruction has been significantly curtailed. The training to be provided by the solicited Education Projects will help restore the balance between in vitro and in vivo approaches to science.
The above analysis is based on input that NIGMS staff has gleaned from several sources:
1. Concerns in this area were raised by Jobe, et al., "The essential role of integrative biomedical sciences in protecting and contributing to the health and well being of our nation," in the Physiologist 37, 79-86 (1994), reprinted in the Pharmacologist 40, 31-37, 1998. Similar concerns at the international level are raised in "The fall and rise of in vivo pharmacology," Trends in Pharmacological Sciences 23, 12-18, 2002.
2. Public affairs briefing materials on the issues are available from the American Society for Pharmacology and Experimental Therapeutics and the American Physiological Society through their respective websites: http://www.aspet.org and http://www.the-aps.org. A broad coalition of scientists, represented by organizations including the American Association of Anatomists, the American Physiological Society, the American Society for Clinical Pharmacology and Therapeutics, the American Society for Nutritional Sciences, the American Society for Pharmacology and Experimental Therapeutics, the PHARMA Foundation, the Safety Pharmacology Society, and the Society of Toxicology, have endorsed a joint statement of support for increased research and training in Systems and Integrative Biology. Input from other societies has included the American Association of Veterinary Medical Colleges, the Institute for Laboratory Animal Research, and several international pharmacological societies.
3. Meetings between NIGMS staff and representatives of academia and industry have occurred on multiple occasions, including but not limited to a meeting organized by NIGMS titled, "What IS training in the Pharmacological Sciences?" held on the NIH campus, August 8-9, 2002. Details of the meeting and an Executive Summary Report are available at the following URL: http://www.nigms.nih.gov/news/meetings/pharmscitraining/. Additional summary reports were published in the journals, Molecular Interventions 2(5), 270-275, 2002 and Pharmaceutical Research 19(12), 1773-1774, 2002. NIGMS staff also participated in a workshop organized by the Life Sciences Research Office (LSRO), "The Status and Future of Integrative & Organ Systems Sciences," held on October 20-21, 2002. See: http://lsro.org/ioss/frames_ioss_home.html.
GOALS FOR THE PROPOSED EDUCATION PROJECT(S):
Establish a strong connection between in vitro, organ function in situ, and in vivo results.
Introduce students to the role of in vivo methods in translational research and safety and efficacy in drug discovery and development.
Expose students to multiple animal models and reasons for selecting a given model for a particular purpose.
Provide significant hands-on experience with small animal models and at least some exposure to larger animal models.
Provide reinforced training in responsible conduct of research, including improved ability to articulate the need for such work in health research.
Improve the ability of students to communicate with other scientists across a broad spectrum of research activities.
Stimulate development at institutions through the return of interested students and the encouragement of institutional commitment.
The project should develop an appropriate and innovative program of instruction in Systems and Integrative Pharmacology to be conducted during an intensive short course (e.g., 2-3 weeks) to be offered in the summer. Other course durations and offering times may be suggested. This program should satisfy the needs of the students for the introduction of basic concepts as well as the acquisition of initial hands-on skills with a number of organ system and intact animal model
methods. A combination of lectures, laboratories, demonstrations, and seminars may be employed. The development of novel educational tools and approaches is encouraged. This program embraces physiology and other related areas of integrative and organ systems sciences as they form the underpinnings of in vivo pharmacology.
The target audience for the Education Project(s) includes scientists at all advanced levels of training and career development, although a concentration on students at the graduate level may be appropriate. These projects will not support K-12 or undergraduate education. Graduating seniors who expect to enter graduate school in the near future may be included. Participation of students supported by NIH predoctoral training grants in the Pharmacological Sciences is highly
encouraged, but the training should be available to other students as well. Inclusion of students pursuing MD, PharmD, DVM, and other advanced degrees, as well as PhD degree students, is encouraged. Inclusion of postdoctoral fellows and established researchers who are seeking new directions is also appropriate. The course should be open to students from industry and government as well as academia.
The project should develop plans for recruiting and selecting students to participate in the project. These plans should be structured in a way that encourages integration of the proposed short course experience into the program of training of students at their home institutions.
Agreements with a number of home institutions might be developed to encourage participation of their students, but the course should not be limited to institutions with whom such agreements exist. Projects may (but are not required to) include components that provide matching of students to follow-up academic or industrial experiences that will provide additional training in integrative and organ systems pharmacology. It would be useful to establish collaborations with a number of industrial organizations expressing willingness to accept the number of students to be placed. It would be useful to obtain commitments from academic mentors indicating how the student will be able to utilize their training after the course.
Projects should include plans to evaluate the effectiveness of short course and other activities and to further refine the program in subsequent years of the project period.
Projects should describe plans to disseminate the educational tools and approaches developed by this project to additional institutions. Provision of handout materials via websites and access to lectures via streaming video or other technologies is highly encouraged. Access to archival video material is desirable.
SUGGESTED SHORT COURSE TOPICS:
The following list of topics for inclusion in a short course is suggestive only, not inclusive or prescriptive:
Care and use of animals
Responsible conduct of research involving animal subjects
Role of animal subjects in translational research
Selection of appropriate models for human diseases
Routes of drug administration and sampling
Pharmacokinetics and pharmacodynamics, including ADME studies
Small animal surgery and tissue sample recovery for histology
Cardiovascular, renal, and pulmonary function monitoring in restrained and unrestrained live animals
Small animal reproduction and characterization of genetically modified organisms
Small animal neuropharmacology and behavioral monitoring
Large animal laboratories, demonstrations, videos, and simulations
Primate model lectures, videos, remote data, and simulations
Imaging applications in pharmacology
Toxicological methodology
Integration of cellular and molecular information with organ systems and whole organisms data
The short course should not merely cover the necessary techniques to execute a particular protocol. Rather, it should provide an understanding of the strengths and weaknesses of particular models and the important concepts needed to design meaningful experiments. The course should provide not only familiarity with systems that are inherently integrative in their function, but should enhance the ability of the scientist to integrate information about systems.
Although much attention may be focused on mouse and rat models, inclusion of other species in some capacity is required.
MECHANISM OF SUPPORT
This RFA will use the NIH Education Project (R25) award mechanism. As an applicant you will be solely responsible for planning, directing, and executing the proposed project. This RFA is a one-time solicitation. (It may or may not be reissued at a future date.) Future unsolicited, competing-continuation applications based on this project will compete with all investigator-initiated applications and will be reviewed according to the customary peer review procedures.
The anticipated award date is April 1, 2005, for short courses that will be first offered in the summer, 2005.
This RFA does not use the modular budgeting format. A detailed categorical budget should be proposed. This program does not require cost sharing as defined in the current NIH Grants Policy Statement at http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part2.htm.
FUNDS AVAILABLE
The NIGMS intends to commit approximately $500,000 in FY 2005 to fund 2 to 3 new grants in response to this RFA. An applicant may request a project period of up to 3 years and a budget for direct costs of up to $200,000 per year. Because the nature and scope of the proposed project will vary from application to application, it is anticipated that the size and duration of each award will also vary. Although the financial plans of the NIGMS provide support for this program, awards pursuant to this RFA are contingent upon the availability of funds and the receipt of a sufficient number of meritorious applications.
ELIGIBLE INSTITUTIONS
You may submit (an) application(s) if your institution has any of the following characteristics:
For-profit or non-profit organizations
Public or private institutions, such as universities, colleges, hospitals, and laboratories
Units of State and local governments
Eligible agencies of the Federal government
Domestic institutions/organizations
Foreign institutions are not eligible to apply; however, foreign scientists may participate as instructors. Foreign organizations may participate as sponsors for follow-on experiences, such as industrial internships, outside of the scope of the funded project.
INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS
Any individual with the skills, knowledge, and resources necessary to carry out the proposed Education Project is invited to work with their organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH programs.
SPECIAL REQUIREMENTS
Requirement for Commitment of Principal Investigator
The Principal Investigator is expected to commit a substantial effort to the organization, oversight, development of materials, and instruction of the short course.
Requirement for Involvement of Multiple Participating Organizations
These Education Project awards will not support curriculum development projects focused on a single institution. For administrative purposes, only one organization may serve as the applicant organization and should coordinate all activities of the project. However, multiple organizations must be committed to the Education Project. It is recommended that the course be run by an organizing committee and that multiple organizations be represented on the organizing committee. The short course may make use of the facilities at multiple organization sites, but this is not essential--appropriate academic, government, independent laboratory, or industrial research facilities should be proposed. Faculty should be drawn from multiple organizations.
Inclusion of faculty members representing academia, industry, and government, is encouraged. The participation of individual industrial sponsors or industrial organization sponsors is encouraged. The inclusion of letters indicating commitment of the target community to the project is recommended.
Recruitment of Students
Advertising, application procedures, and selection of students will be a grantee responsibility. The students should be drawn from multiple institutions, not just the grantee institution, and efforts should be made to insure recruitment of a diverse student pool. Recruitment plans must address inclusion of disadvantaged students, including under-represented minorities.
Animal Welfare Assurances
The applicant organization must provide assurance that all students receive appropriate training in the Responsible Conduct of Research involving Animal Subjects prior to beginning any work with animal subjects. If students have received such training at their home institutions, the organization must obtain appropriate documentation of this fact. If students have not received such training at their home institutions, the organization must provide this training. In either case, the organization should provide any additional training necessary for students to meet assurance requirements for use of animals at the host site. Plans to meet assurance requirements should be described in the application. Documentation of assurance will be requested at the time of award.
WHERE TO SEND INQUIRIES
We encourage inquiries concerning this RFA and welcome the opportunity to answer questions from potential applicants. Inquiries may fall into three areas: scientific/research, peer review, and financial or grants management issues:
Direct your questions about programmatic issues to:
Direct your questions about peer review issues to:
Direct your questions about financial or grants management matters to: