Small Research Grant (R03) mechanism for discovering etiological and pathophysiological mechanisms underlying a set of chronic, comorbid conditions associated with temporomandibular joint and muscle disorders (TMJMDs)

Small Research Grant (R03) mechanism for discovering etiological and pathophysiological mechanisms underlying a set of chronic, comorbid conditions associated with temporomandibular joint and muscle disorders (TMJMDs) is sponsored by National Institutes of Health (NIH). This opportunity supports mission-aligned projects and measurable outcomes.

Expired PA-06-267: Temporomandibular Joint and Muscle Disorders: Pathophysiological Mechanisms Linking Comorbid Conditions (R03) This notice has expired. Check the NIH Guide for active opportunities and notices. Part I Overview Information Department of Health and Human Services Participating Organizations National Institutes of Health (NIH), ( http://www.

nih. gov ) Components of Participating Organizations National Institute of Dental and Craniofacial Research (NIDCR), ( http://www. nidcr.

nih. gov ) National Institute of Neurological Disorders and Stroke (NINDS), ( http://www. ninds.

nih. gov Office of Research on Women’s Health (ORWH), ( http://orwh. od.

nih. gov ) Joint and Muscle Disorders: Pathophysiological Mechanisms Linking Comorbid This is a reissue of PA-06-188 which was previously released on March 1, 2006. Update: The following update relating to this announcement has been issued: September 17, 2007 - Expiration Date adjusted to accommodate recent changes to standing submission deadlines, per NOT-OD-07-093.

August 31, 2006 - See Notice NOT-DE-06-003 outlining additional information. NOTICE: Applications submitted in response to this Funding Opportunity Announcement (FOA) for Federal assistance must be submitted electronically through Grants. gov ( http://www.

grants. gov ) using the SF424 Research and Related (R&R) forms and the SF424 (R&R) Application Guide. APPLICATIONS MAY NOT BE SUBMITTED IN PAPER FORMAT.

This FOA must be read in conjunction with the application guidelines included with this announcement in Grants. gov/Apply for Grants (hereafter called Grants. gov/Apply).

A registration process is necessary before submission and should be started at least four weeks in advance of the planned submission. See Section Two steps are required for on time submission: 1) The application must be successfully received by Grants. gov no later than 5:00 p.

m. local time (of the applicant institution/organization) on the submission/receipt date (see Key Dates below). 2) Applicants must complete a verification step in the eRA Commons within two business days of notification from NIH.

Note: Since email can be unreliable, it is the responsibility of the applicant to periodically check on their application status in the Program Announcement (PA) Number: PA-06-267 Catalog of Federal Domestic Assistance Number(s) 93. 121 (NIDCR), 93. 853 (NINDS) Release/Posted Date: March 24, 2006 Opening Date: May 2, 2006 Date(s): Standard dates apply, please see: http://grants1.

nih. gov/grants/funding/submissionschedule. htm#reviewandaward Peer Review Date(s): Standard dates apply, please see: http://grants1.

nih. gov/grants/funding/submissionschedule. htm#reviewandaward Council Review Date(s): Standard dates apply, please see: http://grants1.

nih. gov/grants/funding/submissionschedule. htm#reviewandaward Earliest Anticipated Start Date(s): Standard dates apply, please see: http://grants1.

nih. gov/grants/funding/submissionschedule.

htm#reviewandaward Additional Information To Be Available Date (Activation Expiration Date: March 2, 2009 (now May 8, 2009 per NOT-OD-07-093 ) Additional Overview Content The purpose of this Funding Opportunity Announcement (FOA) is to stimulate research on discovering etiological and pathophysiological mechanisms underlying a set of chronic, comorbid conditions associated with temporomandibular joint and muscle disorders (TMJMDs).

TMJMDs are a complex collection of diseases involving one or more tissues of the TMJ and facial musculature. Primary symptoms include chronic pain in facial muscles and limited and painful movement of the jaw.

In addition, these and other symptoms of TMJMD can occur together with other chronic illnesses such as fibromyalgia, atypical face pain, trigeminal neuralgia, chronic fatigue syndrome, multiple chemical sensitivity, irritable bowel syndrome, complex regional pain syndrome, migraine headache, speech hearing, swallowing, balance, smell, and taste disorders, and certain cardiovascular diseases.

This program announcement seeks research applications that use state-of-the-art, multidisciplinary and interdisciplinary approaches to discover molecular, physiological, and behavioral mechanisms responsible for the overlapping symptoms manifested in the set of disorders that may co-exist with TMJMD.

These applications may have as their research focus the chronic, comorbid conditions themselves or TMJMDs, provided that the aims and goals of the project are to discover biological mechanisms linking the comorbidities.

While the overarching goal of this announcement is to arrive at a better understanding of potential mechanisms underlying TMJMDs as related to the variety of comorbidities associated with them, it is expected that no single research project will be able to accomplish this. Applicants are, therefore, encouraged to focus their attention on a particular pathway and a specific disease that is comorbid with TMJMD.

The R03 grant mechanism supports different types of projects including pilot and feasibility studies; secondary analysis of existing data; small, self-contained research projects; development of research methodology; and development of new research technology. The R03 is intended to support small research projects that can be carried out in a short period of time with limited resources. The R03 is not renewable.

The total amount to be awarded and the anticipated number of awards. Awards issued under this FOA are contingent upon the availability of funds and the submission of a sufficient number of meritorious applications. Budgets for direct costs of up to $50,000 per year and a project durat ion of up to two years may be requested for a maximum of $100,000 direct costs over a two-year project period.

The types of mechanisms : This FOA will utilize the Small Research Grant (R03) mecha nism and runs in parallel with FOA s of identical scientific scope, PA-06-188 that solicits applications under the R01 grant mechanism and PA- 06 -268 that solicits applications under the R21 mechanism .

Eligible organizations: For-profit organizations; non-profit organizations; public or private institutions, such as universities, colleges, hospitals, and laboratories; units of State government; units of local governm ent; eligible institutions of the Federal government; domestic institutions; foreign institutions; faith-based or community-based organizations; units of State Tribal government; and units of Local Tribal government.

Eligible Project Director/Principal Investigators (PD/PIs): Individuals with the skills, knowledge, and resources necessary to carry out the proposed research are invited to work with their institution to develop an application for support.

Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply Applicants may submit more than one application, provided each application is scientifically distinct. See Section IV. 1 for application materials.

For general information on SF424 (R&R) Application and Electronic Submission, see the following Web sites: SF424 (R&R) Application and Electronic Submission Information: http://grants. nih. gov/grants/funding/424/index.

htm General information on Electronic Submission of Grant Applications: http://era. nih. gov/ElectronicReceipt/ Telecommunications for the hearing impaired is available at: TTY 301-451-5936.

Part I Overview Information Part II Full Text of Announcement Section I. Funding Opportunity Section II. Award Information Section III.

Eligibility Information 2. Cost Sharing or Matching 3. Other - Special Eligibility Criteria Section IV.

Application and Submission 1. Request Application Information 2. Content and Form of Application Submission 3.

Submission Dates and Times A. Submission, Review, and Anticipated Start Dates B. Sending an Application to the NIH C.

Application Processing 4. Intergovernmental Review 6. Other Submission Requirements Section V.

Application Review 2. Review and Selection Process A. Additional Review Criteria B.

Additional Review Considerations D. Sharing Research Resources 3. Anticipated Announcement and Award Dates Section VI.

Award Administration 2. Administrative and National Policy Requirements 1. Scientific/Research Contact(s) 2.

Peer Review Contact(s) 3. Financial/Grants Management Contact(s) Section VIII. Other Information - Required Federal Citations Part II - Full Text of Announcement Section I.

Funding Opportunity Description Nature of the research opportunity - The purpose of this FOA is to encourage research leading to the discovery of possible etiological and pathophysiological mechanisms underlying a set of chronic disorders that may overlap with temporomandibular joint and muscle disorder (TMJMD).

Investigators with expertise in TMJMD and those with specific expertise in research areas related to the overlapping, comorbid conditions are encouraged to work together in carrying out cutting-edge research projects designed to uncover biological mechanisms responsible for comorbidities associated TMJMDs are a complex set of diseases involving one or more tissues of the face and TMJ.

The primary symptoms of TMJMD may include chronic pain in facial muscles and limited and painful movement of the jaw.

In addition, these and other symptoms of TMJMD may occur together with other chronic disorders such as fibromyalgia; atypical facial pain; trigeminal neuralgia; chronic fatigue syndrome; multiple chemical sensitivity; irritable bowel syndrome; sleep disorders; complex regional pain syndrome; migraine headache; speech, hearing (including tinnitus) swallowing, balance, smell, and taste disorders; affective disorders; and certain cardiovascular diseases.

The possible overlap of these other conditions with TMJMD suggests several possibilities: TMJMD coexists with other chronic diseases; TMJMD is the somatization of one or more of these conditions; TMJMD results from effects of the other chronic disorders; and/or TMJMD contributes to these other conditions.

This initiative seeks research applications that will use multidisciplinary and interdisciplinary approaches to sort out these possibilities by discovering molecular, physiological, and behavioral mechanisms responsible for the overlapping symptoms and disorders that may coexist with TMJMD.

These applications may have as their research focus the chronic, comorbid conditions themselves or TMJMDs, provided that the aims and goals of the project are to discover biological mechanisms linking the comorbidities.

While the overarching goal of this announcement is to arrive at a full understanding of the mechanisms underlying TMJMDs and the variety of comorbidities associated with them, it is expected that no single research project will be able to accomplish this. Applicants, therefore, are encouraged to focus their attention on a particular pathway and a specific disease that is comorbid with TMJMD.

Background - TMJMD is a complex heterogeneous disease. It likely represents a collection of disorders with varying etiologies, affecting the tissues of the masticatory muscles and the temporomandibular joint. Due to this complexity and our lack of a complete understanding of the underlying mechanisms of disease onset and progression, the treatment of some patients with TMJMD currently is less than satisfactory.

The etiology of complex disorders like TMJMD may involve the interaction of genetic and environmental influences. In addition, it may be appropriate to view TMJMD as a biopsychosocial disorder, not only when considering diagnosis and treatment, but also in the context of pathological mechanisms associated with the disease and other diseases that may coexist with TMJMDs as comorbidities.

Peripheral defects in muscle function, abnormal neurotransmission, central integration of sensory and motor inputs, and the societal and cognitive influences on these processes, may all interact and influence the disease process and expression of the associated comorbidities.

The major symptoms of TMJMD are chronic myofacial pain particularly in the muscles of mastication, restricted range of jaw motion, jaw locking, and abnormal popping and clicking noises in the TMJ, although this latter symptom is not, by itself, either predictive or diagnostic of TMJMD.

In addition, other symptoms are known to occur in this disorder such as pain in the joint itself and in the area surrounding and radiating from the joint including the ear, neck, shoulder, and back; vertigo/balance problems; hearing loss, tinnitus; taste and smell problems; chronic headache; blurred or double vision; sleep disturbances; and difficulty in swallowing and/or speech.

Besides these symptoms, certain psychiatric disturbances (psychopathologies) may be associated with TMJMD and may include depression, anxiety disorders, and substance abuse. While these other symptoms and conditions are clearly not diagnostic of TMJMD, they are associated with other chronic painful disorders and may have an important role in developing treatment approaches for TMJMD patients.

For example, similar psychiatric disorders have been associated with TMJMD, fibromyalgia (FM), chronic fatigue syndrome (CFS), and irritable bowel syndrome (IBS). Interestingly, the psychiatric disorders are most often associated with the myogenous form of TMJMD (i.e. TMJMD characterized by chronic muscle pain) and may reflect the effects of prolonged chronic pain on the emotional status of the individual.

TMJMD patients often present with symptoms of other chronic painful conditions, such as FM, CFS, IBS, multiple chemical sensitivities, and cardiovascular abnormalities to name a few. As an example, both TMJMD and FM patients suffer from similar symptoms: muscle pain or tenderness, sleep disturbances, debilitating headaches, and difficulty in concentrating. The degree of overlapping symptoms and comorbid conditions is not trivial.

Studies suggest that between 13 and 18% of TMJMD patients meet the diagnostic criteria for FM. Conversely, about 75% of FM patients meet the criteria for myofacial TMJMD. Patients with IBS have been diagnosed at similar rates with comorbid TMJD (16%), CFS (14%), and FM (28-65%).

While some of the apparent comorbidity may be due to diagnostic ambiguity, it is clear that patients with these disorders have similar and multiple symptoms that characterize the various disorders. It is important to understand the basis for the links between these comorbidities in order to develop more effective treatment and possible prevention strategies for TMJMD.

However, the etiological and pathological mechanisms linking TMJMD and these comorbid conditions are unclear. In general they may involve abnormal responses of common homeostatic mechanisms, i.e. processes that help the body to return to original set points after a disruptive stimulus.

Alternatively, or in addition, the mechanisms may relate to allostatic processes, i.e. the adaptation to new set points in the continued presence of a stimulus or an altered environment. In addition, failed or repeated allostatic processes, i.e. the allostatic load, may account for these comorbidities. Most of these regulatory systems control a systemic, physiological response and a central behavioral, response.

The concept of faulty adaptive processes is in agreement with a shift in thinking in recent years to a more central nervous system focus as the cause of TMJMD (excluding TMJMD associated with traumatic injury) rather than simply a peripheral one employing local homeostatic mechanisms.

An additional consideration is that there is an increased prevalence of these comorbid disorders in women, indicating that sex steroids and gender may play an important, but complex role in the common pathophysiology. For example, there is an increased prevalence of TMJMD and FM in women, yet TMJMD patients are usually in their childbearing years while FM is usually diagnosed later in life.

Regardless of the mechanisms responsible for the comorbidities associated with TMJMD, a more precise determination of the phenotypes of the diseases will be critical in order to clearly identify subsets of TMJMD patients and the specific comorbid conditions associated with TMJMD.

While several distinct pathological mechanisms may account for the comorbidities seen in association with TMJMD, many seem to ultimately involve abnormal functioning of feedback circuits (both positive and negative).

These may include disturbances in the following: the hypothalamic-pituitary-adrenal (HPA) axis, the classical stress-response system; immune and neuroimmune function; centrally regulated biological clocks; autonomic nervous system function; and specific neurotransmitter system regulation.

These and other mechanisms may work alone or in concert to cause the collection of comorbid conditions The cooperation of researchers with a common interest in TMJMD and those with specific expertise in research areas related to the overlapping comorbid conditions and symptoms found in TMJMD is needed in order to arrive at definitive answers to the underlying mechanisms involved in TMJMD and the variety of comorbidities noted.

Information from the fields of neurology, psychiatry, cardiology, genomics, endocrinology, epidemiology, rheumatology, and communicative disorders, to name a few, will be required to develop and test hypotheses relating to the mechanisms that can account for the cluster of comorbidities.

Technical expertise in behavioral science, genomic and proteomic approaches, biomedical imaging, electrophysiology, and molecular biology will be necessary to carry out cutting-edge experiments designed to uncover biological mechanisms responsible for overlapping symptoms and comorbid conditions associated with TMJMD.

While the overarching goal of this announcement is to arrive at a clearer understanding of the mechanism underlying TMJMD and the variety of comorbidities associated with it, it is expected that no single research project will be able to accomplish this.

Applicants are, therefore, encouraged to focus their attention on a particular pathway and a specific disease that Scientific knowledge to be achieved - This FOA will stimulate research that will increase our knowledge of the etiological and pathological mechanisms underlying comorbidity in somatic syndromes like TMJMD.

It will be important to identify the regulatory systems and the altered functions of these systems that are important in the expression of comorbidity. Knowledge of both physiological and behavioral responses that are central in eliciting comorbidity will be gained; the molecules and cellular pathways underlying these responses will be identified as well.

Objectives of this research program - The objectives of this FOA are to stimulate research that will: 1) identify molecules, cellular pathways, physiologies, and behaviors that are responsible for comorbid conditions that may be associated with TMJMD; 2) determine the pathogenic mechanisms by which these factors lead to the comorbidities; 3) determine molecules and pathways that may serve as novel therapeutic targets aimed at treating these comorbid conditions and/or preventing them; 4) identify biomarkers or diagnostics that will differentiate refractory TMJMD and comorbid conditions from those disorders which spontaneously remit or are successfully treated by conventional means.

Identify types of research and experimental approaches that are being sought - This FOA seeks applications that will use basic, behavioral, epidemiological, and clinical research approaches in order to define causative factors and characterize pathogenic mechanisms that may be shared between comorbid conditions and TMJMD.

This FOA seeks a broad range of experimental approaches to this problem and may include clinical, molecular, cellular, and animal studies. The use of global approaches such as a systems biology approach and the utilization of genomic and proteomic techniques also are encouraged.

Investigators with expertise in the fields of neurobiology, immunology, neurochemistry, endocrinology, rheumatology, cognitive and behavioral neuroscience, sensory and motor systems, neurology, and bioinformatics will be needed to discover biological mechanisms underlying comorbidity.

Examples of research topics - Examples of research topics may include, but are not limited to the following, as they relate to TMJMD and comorbidities: Identification of molecular mechanisms in the central nervous system that modulate peripheral nociceptive neurotransmission Genomic studies that identify genes and gene polymorphisms that are causative or produce risk factors for comorbid conditions and TMJMD Effects of inflammatory pain and proinflammatory cytokines on hypersensitivity of central pain modulatory Influence of hypersensitive nociceptive Identification of molecules and pathways that regulate or disrupt circadian rhythms and other biological Neuroimaging studies to identify brain regions and nerve tracts active in patients with TMJMD and comorbid Studies to determine the influence of the activity of nociception pathways on other sensory and motor systems including taste, smell, hearing (including tinnitus) balance, speech, swallowing, Use of animal models to examine the effects of chronic pain on affective behaviors Studies on the influence of sex hormones on circadian rhythms, HPA axis, and autonomic nervous system Influence of trigeminal nerve activity on the autonomic nervous system and the HPA axis Molecular studies on the effects of neural plasticity in pain pathways that affect other sensory and motor Clinical research approaches that help to discover behavioral changes influencing and influenced by TMJD SCOPE: The common characteristic of the small grant is provision of limited funding for a short period of time.

Examples of the types of projects that ICs support with the R03 include the following: Pilot or feasibility studies Secondary analysis of existing data Small, self-contained research projects Development of research methodology Development of new research technology See Section VIII, Other Information - Required Federal Citations , for policies related to this announcement. Section II. Award Information 1.

Mechanism(s) of Support This Funding Opportunity Announcement (FOA) invites applications for small research (R03) projects that can be carried out in a short period of time with limited resources. The applicant will be solely responsible for planning, directing, and executing the proposed project. This FOA uses just-in-time concepts.

It also uses the modular budget formats (see the Modular Applications and Awards section of the NIH Grants Policy Statement . All applications submitted in response to this FOA must use the modular budget format.

Specifically, if you are submitting an application with direct costs in each year of $250,000 or less (excluding consortium Facilities and Administrative [F&A] costs), use the PHS398 Modular Budget component provided in the SF424 (R&R) Application Package and SF424 (R&R) Application Guide (see specifically Section 5. 4, Modular Budget Component, of the Application Guide).

Competing renewal (formerly competing continuation ) applications will not be accepted for the R03 grant mechanism. Small grant support may not be used for thesis or dissertation research. Up to two resubmissions (formerly revisions/amendments") of a previously reviewed small grant application may be submitted as defined NOT-OD-05-046 http://grants.

nih. gov/grants/guide/notice-files/NOT-OD-05-046. html For specific information about the R03 programs, see: http://grants.

nih. gov/grants/funding/r03. htm .

Although the financial plans of the ICs provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds and the submission of a sufficient number of meritorious applications.

A project period of up to two years and a budget for direct costs of up to two $25,000 modules, or $50,000 per year, may be requested (i.e., a maximum of $100,000 over two years in four modules of $25,000 each). Commensurate Facilities and Administrative (F&A) costs are allowed. F&A costs requested by consortium participants are not included in the direct cost limitation, See NOT-OD-05-004 , Section III.

Eligibility Information 1. A.

Eligible Institutions You may submit an application(s) if your organization has any of the following characteristics: For-profit organizations; Non-profit organizations; Public or private institutions, such as universities, colleges, hospitals, Units of State government; Units of local government; Eligible institutions of the Federal government; Faith-based or community-based organizations; Units of State Tribal government; and Units of Local Tribal government.

1. B. Eligible Individuals Any individual with the skills, knowledge, and resources necessary to carry out the proposed research is invited to work with his/her institution 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 support. R03 eligibility is limited to new investigators at NIDCR . R03 eligibility is open to new and prior-funded investigators at NINDS .

See the following site for details of NIDCR and NINDS policies regarding R03 applications: http://grants. nih. gov/grants/funding/r03.

htm 2. Cost Sharing or Matching This program does not require cost sharing as defined in the current NIH Grants Policy Statement . 3.

Other-Special Eligibility Criteria Applicants may submit more than one application, provided each application is scientifically distinct. Section IV. Application and To download an Application Package and Application Guide for completing the SF424 (R&R) forms for this FOA, link to http://www.

grants. gov/Apply/ and follow the directions provided on that Web site. A one-time registration is required for institutions/organizations at both: Grants.

gov ( http://www. grants. gov/GetStarted ) NIH eRA Commons ( http://era.

nih. gov/ElectronicReceipt/preparing. htm ) Project Directors/Principal Investigators (PD/PIs) should work with their institutions/organizations to make sure they are registered in the NIH eRA Several additional separate actions are required before an applicant institution/organization can submit an electronic application, as follows: 1) Organization/Institutional Registration in Grants.

gov/Get Your organization will need to obtain a Data Universal Number System (DUNS) number and register with the Central Contractor Registration (CCR) as part of the Grants. gov registration process. If your organization does not have a Taxpayer Identification Number (TIN) or Employer Identification Number (EIN), allow for extra time.

A valid TIN or EIN is necessary for CCR registration. The CCR also validates the EIN against Internal Revenue Service records, a step that will take an additional one to two business days. Direct questions regarding Grants.

gov registration to: Grants. gov Customer Support Business Hours: M-F 7:00 a. m.

- 9:00 p. m. Eastern Time 2) Organization/Institutional Registration in the eRA Commons To find out if an organization is already Commons-registered, see the " List of Grantee Organizations Registered in NIH eRA Commons.

Direct questions regarding the Commons registration to: Phone: 301-402-7469 or 866-504-9552 (Toll Free) Business hours M-F 7:00 a. m. 8:00 p.

m. Eastern Time 3) Project Director/Principal Investigator (PD/PI) Registration in the NIH eRA Commons: Refer to the NIH eRA Commons System (COM) Users The individual designated as the PD/PI on the application must also be registered in the NIH eRA Commons. It is not necessary for PDs/PIs to register with The PD/PI must hold a PD/PI account in the Commons and must be affiliated with the applicant organization.

This account cannot have any other role attached to it other than the PD/PI. This registration/affiliation must be done by the Signing Official (SO) or their designee who is already registered in the Commons. Both the PD/PI and SO need separate accounts in the NIH eRA Commons since both are required to verify the application.

Note that if a PD/PI is also an NIH peer-reviewer with an Individual DUNS and CCR registration, that particular DUNS number and CCR registration are for the individual reviewer only. These are different than any DUNS number and CCR registration used by an applicant organization.

Individual DUNS and CCR registration should be used only for the purposes of personal reimbursement and should not be used on any grant applications submitted to the Federal Several of the steps of the registration process could take four weeks or more. Therefore, applicants should immediately check with their business official to determine whether their institution is already registered in both Grants. gov and the Commons .

The NIH will accept electronic applications only from organizations that have completed all necessary registrations. 1. Request Application Information Applicants must download the SF424 (R&R) application forms and SF424 (R&R) Application Guide for this FOA through Grants.

gov/Apply . Note: Only the forms package directly attached to a specific FOA can be used. You will not be able to use any other SF424 (R&R) forms (e.g., sample forms, forms from another FOA), although some of the Attachment files may be useable for more than one FOA.

For further assistance contact GrantsInfo, Telephone 301-710-0267, Email: Telecommunications for the hearing impaired: TTY 301-451-5936. 2. Content and Form of Application Submission Prepare all applications using the SF424 (R&R) application forms and in accordance with the SF424 (R&R) Application Guide The SF424 (R&R) Application Guide is critical to submitting a complete and accurate application to NIH.

There are fields within the SF424 (R&R) application components that, although not marked as mandatory, are required by NIH ( e.g., the Credential log-in field of the Research & Related Senior/Key Person Profile component must contain the PD/PI’s assigned eRA Commons User ID ). Agency-specific instructions for such fields are clearly identified in the Application Guide.

For additional information, see Tips and Tools for Navigating Electronic Submission on the front page of Electronic Submission of Grant Applications . The SF424 (R&R) application is comprised of data arranged in separate components. Some components are required, others are optional.

The forms package associated with this FOA in Grants. gov/APPLY will include all applicable components, required and optional.

A completed application in response to this FOA will include the following components: SF424 (R&R) (Cover component) Research & Related Project/Performance Site Locations Research & Related Other Project Information Research & Related Senior/Key Person PHS398 Cover Page Supplement Note: While both budget components are included in the SF424 (R&R) forms package, the NIH R03 uses ONLY the PHS 398 Modular Budget.

(Do not use the detailed Research & Related Budget.) Several special provisions apply to applications submitted by foreign organizations: Charge back of customs and import fees is not allowed. Format: every effort should be made to comply with the format specifications which are based upon a standard U.S. paper size of 8.

5 x 11 within each Funds for up to 8% administrative costs (excluding equipment) may be requested. Organizations must comply with Federal/NIH policies on human subjects, animals, Organizations must comply with Federal/NIH biosafety and biosecurity regulations. See Section VI.

2. , Administrative and National Security Proposed research should provide a unique research opportunity not available in the United States. 3.

Submission Dates and Times 3. A. Submission, Review, and Anticipated Opening Date: May 2, 2006 Letter of Intent Receipt Date(s): Not Applicable Application Submission Date(s): Standard dates apply, please see: http://grants.

nih. gov/grants/funding/submissionschedule. htm Peer Review Date(s): Standard dates apply, please see: http://grants1.

nih. gov/grants/funding/submissionschedule. htm#reviewandaward Council Review Date(s): Standard dates apply, please see: http://grants1.

nih. gov/grants/funding/submissionschedule. htm#reviewandaward Earliest Anticipated Start Date: Standard dates apply, please see: http://grants1.

nih. gov/grants/funding/submissionschedule. htm#reviewandaward A letter of intent is not required for the funding 3.

B. Electronic Transmission of an Application to the To submit an application in response to this FOA, applicants should access this FOA via http://www. grants.

gov/Apply and follow steps 1-4. Note: Applications must only be submitted electronically . PAPER APPLICATIONS WILL NOT BE ACCEPTED.

3. C. Application Processing Applications may be submitted on or after the opening date and must be successfully received by Grants.

gov no later than 5:00 p. m. local time (of the applicant institution/organization) on the application submission/receipt date(s).

(See Section IV. 3. A.

for all dates.) If an application is not submitted by the receipt date(s) and time, the application may be delayed in the review process or not reviewed. Upon receipt, applications will be transferred from Grants.

gov to the NIH Electronic Research Administration process for validation. Both the PD/PI and the Signing Official for the organization must verify the submission via Commons within two (2) business days of notification of the NIH validation. Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review, NIH.

Incomplete applications There will be an acknowledgement of receipt of applications from Grants. gov and the Commons . Information related to the assignment of an application to a Scientific Review Group is also in the Commons .

The NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial merit review unless the applicant withdraws the pending application. The NIH will not accept any application that is essentially the same as one already reviewed.

This does not preclude the submission of an application already reviewed with substantial changes, but such application must include an Introduction addressing the previous critique. Note that such an application is considered a "resubmission" for the SF424 (R&R). 4.

Intergovernmental Review This initiative is not subject to intergovernmental All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Pre-Award Costs are allowable.

A grantee may, at its own risk and without NIH prior approval, incur obligations and expenditures to cover costs up to 90 days before the beginning date of the initial budget period of a new or competing renewal award if such costs: are necessary to conduct the project and would be allowable under the grant, if awarded, without NIH prior approval.

If specific expenditures would otherwise require prior approval, the grantee must obtain NIH approval before incurring the cost. NIH prior approval is required for any costs to be incurred more than 90 days before the beginning date of the initial budget period of a new award. The incurrence of pre-award costs in anticipation of a competing or non-competing