MOUSE MODELS OF DIABETIC COMPLICATIONS CONSORTIUM
						
Release Date:  October 31, 2000

RFA:  DK-01-009 (This RFA has been renewed, see RFA-DK-05-011)

National Institute of Diabetes and Digestive and Kidney Diseases
National Heart, Lung, and Blood Institute
National Eye Institute
National Institute of Dental and Craniofacial Research
Juvenile Diabetes Foundation International

Letter of Intent Receipt Date:  February 28, 2001
Application Receipt Date:       March 28, 2001

PURPOSE

The intent of this initiative is to assemble a cross-disciplinary Mouse 
Models of Diabetic Complications (MMDC) Consortium to develop innovative 
mouse models that closely mimic the human complications of diabetes. 
Complications to be examined include diabetic kidney disease, retinopathy, 
neuropathy, micro- and macrovascular disease, peripheral vascular disease, 
hypertension, impaired wound healing, diabetic cardiomyopathy, abnormalities 
of the coagulation system, urinary tract infection, oral diseases, and 
altered gastrointestinal and bladder function.  The first goal of this 
Consortium is to generate animal models that will be useful for studying 
disease pathogenesis, prevention, and treatment.  The second goal of this 
Consortium is to test the role of candidate genes or chromosomal regions that 
emerge from genetic studies of human diabetic complications, particularly 
diabetic kidney disease and accelerated cardiovascular diseases.  Each Unit 
in the Consortium must contain expertise in mouse genetic engineering, organ-
specific phenotyping in the mouse, and at least one diabetic complication.  
The Consortium will define standards, including gene expression profiling, to 
validate each diabetic complication model for its similarity to human 
disease.  The Units will utilize innovative mouse genetic engineering 
techniques to create diabetic mice with altered expression of potential 
target-organ disease genes.  The Units will derive, characterize, validate, 
and use the models for various aspects of basic, developmental, or 
translational research, including testing strategies for prevention, early 
detection, therapy, or diagnostic imaging. 

Consortium Units will have access to resources, information, technologies, 
ideas, and expertise that are beyond the scope of any single research team.  
As mouse models are developed and validated, NIH will provide a mechanism to 
freely disseminate the mouse models and information related to them to the 
scientific community.

HEALTHY PEOPLE 2010

The Public Health Service (PHS) is committed to achieving the health 
promotion and disease prevention objectives of "Healthy People 2010," a PHS-
led national activity for setting priority areas.  This RFA, Mouse Models of 
Diabetic Complications Consortium, is related to the priority areas of 
Diabetes and Chronic Disabling Conditions and to Chronic Renal Disease. 
Potential applicants may obtain a copy of "Healthy People 2010" at 
http://www.health.gov/healthypeople/.

ELIGIBILITY REQUIREMENTS

Applications may be submitted by domestic for-profit and non-profit 
organizations, public and private, such as universities, colleges, hospitals, 
laboratories, units of State and local governments, and eligible agencies of 
the Federal Government.  Foreign institutions are not eligible.  
Racial/ethnic minority individuals, women, and persons with disabilities are 
encouraged to apply as principal investigators.

MECHANISM OF SUPPORT

The administrative and funding instrument to be used for this program will be 
a cooperative agreement (U01), an assistance mechanism (rather than an 
acquisition mechanism) in which substantial NIH scientific and/or 
programmatic involvement with the awardee is anticipated during performance 
of the activity.  Under the cooperative agreement, the NIH purpose is to 
support and/or stimulate the recipient"s activity by involvement in and 
otherwise working jointly with the award recipient in a partner role, but NIH 
is not to assume direction, prime responsibility, or a dominant role in the 
activity.  Details of the responsibilities, relationships, and governance of 
the study to be funded under cooperative agreement(s) are discussed later in 
this document under the section "TERMS AND CONDITIONS OF AWARD."

This RFA is a one-time solicitation.  The total project period for an 
application submitted in response to this RFA may not exceed five years.  The 
anticipated award date is September 30, 2001. 

FUNDS AVAILABLE  

The NIH intends to commit approximately $4,500,000 in FY 2001 to fund up to 
five to six new Mouse Engineering and Phenotyping Units and one Coordinating 
and Bioinformatics Unit in response to this RFA.  The Juvenile Diabetes 
Foundation International intends to commit up to $500,000 to this program.  
Although not participating in the RFA, NIA is interested in co-funding 
applications that include components relevant to aging.  

An applicant for a Mouse Engineering and Phenotyping Unit may request a 
project period of up to five years and budget for direct costs of up to 
$500,000 per year.  Should an applicant plan to include subcontracts to other 
institutions or organizations, only the direct costs of those subcontracts 
will be used to tally the direct costs that apply toward the $500,000 direct 
costs cap, there is no cap on total costs.  An applicant for a Coordinating 
and Bioinformatics Unit may request a project period of up to five years and 
budget for direct costs of up to $300,000 per year.  For further budget 
information, see the section “APPLICATION PROCEDURES.”  Because the nature 
and scope of research proposed in response to this RFA may vary, we 
anticipate that the size of awards will vary also.  Although this program is 
provided for in the financial plans of the NIDDK, awards pursuant to this RFA 
are contingent upon the availability of funds for this purpose and the 
receipt of a sufficient number of applications of outstanding scientific and 
technical merit.  At this time, the NIDDK has not determined whether or how 
this solicitation will be continued beyond the present RFA.

RESEARCH OBJECTIVES

Background

Recognition, prevention, and treatment of diabetic complications are central 
problems in both type 1 and type 2 diabetes mellitus.  In the United States, 
diabetes accounts for 42 percent of all new cases of end-stage renal disease, 
50 percent of all non-traumatic amputations, and the majority of new 
blindness in people ages 20-74.  More than 60 percent of people with diabetes 
are affected by neuropathy.  Macrovascular complications are a major cause of 
morbidity and mortality in diabetes, particularly in patients with 
nephropathy.  Major risk factors for macrovascular complications of diabetes 
are dyslipidemia, hypertension, and cigarette smoking, the same risk factors 
for cardiovascular disease. Cardiovascular disease is the leading cause of 
mortality, morbidity, and disability in the United States and is 
approximately four times higher among diabetic patients compared to non-
diabetics.  Diabetes also markedly increases the risk of developing oral 
complications such as severe periodontitis.  Because diabetic nephropathy 
does not occur in over half of patients with diabetes, and because there is 
significant familial clustering of patients with diabetic nephropathy in the 
African American and Native American communities, there may be one or more 
susceptibility genes for diabetic nephropathy.  Diabetics are also at risk 
for developing genetic forms of hyperlipidemia such as familial 
hypercholesterolemia, suggesting that there may be one or more susceptibility 
genes for this problem.

Genetic technology has advanced so that it is theoretically possible to 
genetically engineer mice that will develop diabetic complications analogous 
to the major human complications of diabetes.  Such accurate models of human 
diabetic complications would be especially valuable to analyze the initiation 
and progression of diabetic complications, to provide the framework for the 
discovery of genes and cellular parameters that generate susceptibility or 
provide resistance, to furnish targets for intervention and treatment, and to 
permit testing of prevention, detection, therapeutic, and imaging strategies 
in the context of a normal tissue environment.  Furthermore, it is now 
possible to more carefully phenotype both human patients and mouse models 
using unbiased techniques such as systematic gene expression.

Several well-characterized mouse models of diabetes exist, however, these 
mice models have been used mainly to study the mechanisms for developing 
diabetes and the metabolic complications.  In contrast, the pathogenesis of 
end-organ damage has received less mechanistic attention. Studies of 
complications have been largely descriptive--often reporting only histologic 
changes.  Time and funding constraints often do not permit an in-depth, 
comprehensive analysis and characterization of diabetic complications 
developed by these mice.  Even fewer models are tested for their response to 
treatment or prevention modalities or their suitability for testing early 
detection or imaging applications.  The genes that confer susceptibility to 
diabetic nephropathy, accelerated atherosclerosis, or cardiovascular disease 
are unknown.  The possible interrelationships between different complications 
(for example, neuropathy and macro- or microvascular disease) that interact 
in diabetic patients have not been systematically studied in animal models.  
The NIH supports many individual projects that involve the derivation or 
study of mice that develop diabetes.  However, at the present time, the NIH 
does not support a coordinated, collaborative effort to produce highly 
accurate mouse models of diabetic complications, particularly for the early 
design, derivation, characterization, and validation phases of model 
building. Furthermore, NIH has not ensured that the models and the data 
relevant to them are readily available to the research community for further 
investigation or application.

Objectives and Scope

The intent of this initiative is to assemble projects for a 
cross-disciplinary, multi-institutional MMDC Consortium whose component teams 
of investigators will refine or derive accurate mouse models of human 
diabetes complications.  The approaches used for generating, characterizing, 
and validating the mice for research will reflect the blend of experience and 
creativity of the Consortium component units and will be originated by these 
investigators.  The Consortium will validate the models for use by the 
research community for a variety of investigations, including for testing 
therapeutic, prevention, early detection, or imaging strategies, and assure 
their availability to the research community.

It is anticipated that up to five or six Mouse Engineering and Phenotying 
Units will be awarded.  Each unit will consist of a cross-disciplinary team 
that may reside, if appropriate, at several institutions.  A separate award 
will support a Coordinating and Bioinformatics Unit.

A. Interactions

The MMDC Consortium, through its component units, Steering Committee, and 
other committees will: 

o Define the parameters by which the diabetic complications will be validated 
(gene expression profiling, pathology, anatomy and functional phenotype, 
imaging, etc.), if necessary, the Consortium may acquire new human phenotypic 
data (for example, by gene profiling),

o Define the complications for which appropriate models exist and select 
those that should be comprehensively characterized and refined, if necessary,

o Define the complications for which no acceptable model exists and a 
model(s) must be designed, derived, and comprehensively characterized, 

o Define standards for phenotyping, treating, and monitoring diabetic mice 
(blood sugar, insulin levels, response to glucose load, hyperinsulinemic 
clamp, etc.),

o Define standards for assessing the impact of glycemic control on the 
development of complications,

o Identify technological impediments to designing accurate models, and select 
strategies to surmount them, 

o Share technological, methodological, and phenotype information both between 
component Units and with the broader research community,

o Share engineered mice between Units so mice can be phenotyped for a variety 
of diabetic complications,

o Decide when a model is sufficiently characterized and validated so that the 
model itself, and all available accompanying data, can be distributed to the 
research community for individual investigator-initiated projects.  

At each step, input will be sought from experts both within the MMDC 
Consortium, within other NIH-sponsored consortia [for example, D-GAP (RFA DK-
97-007), Familial Investigation of Nephropathy of Diabetes (RFA DK-99-005), 
and Mouse Metabolic Phenotyping Centers for Models of Diabetes and its 
Complications (RFA DK-00-014)], and from the broader research community.

The NIH will establish the required distribution systems to disseminate the 
mouse models to the research community.

During the course of the funding period, technologies will improve and the 
rate of progress and scope of research under the cooperative agreement may 
change.  Principal Investigators, in consultation with NIH program staff, 
will be expected to make necessary adjustments to accommodate the changing 
research environment, to remain focused on appropriate goals, to maintain 
excellent coordination with the other projects funded under this RFA, and to 
incorporate new technological advances.

B. Mouse Engineering and Phenotyping Units

Each Unit will be a self-assembled group of investigators from one or more 
institutions who contribute to the MMDC Consortium a unique blend of 
complementary research experience.  An applicant team will incorporate an 
appropriate mix of expertise needed to achieve the Unit’s goals and to 
contribute substantially to achieving the overall MMDC Consortium goals.  
Units will be expected to focus on either one or a small number of diabetic 
complications.  Units do not need expertise in all areas of diabetes 
complications.  Each team must contain expertise in mouse genetic 
engineering, organ-specific phenotyping in the mouse, and at least one 
diabetic complication.  Additional areas of expertise may include, but are 
not limited to: mouse genetics, phenotypic, genotypic, and genomic analyses 
of resulting strains, mouse or human pathology, mouse models of human 
diabetic complications, small animal imaging technologies, animal husbandry, 
mechanism, therapy, prevention, early detection, or diagnostic imaging 
research, and the clinical properties of human diabetic complications that 
inform the design of therapy, prevention, and early detection strategies. 

The approaches used to generate, characterize, and validate mouse models will 
reflect the blend of experience and creativity of the component 
investigators.  The following example is intended only to provide broad 
direction and should be considered illustrative, but not restrictive.  An 
individual application might:

1. Propose standards for validating a particular diabetic complication.  If 
insufficient information is available, the Unit may propose to obtain more 
human anatomic, pathologic, or gene expression information from existing 
databases.

2. Review the literature for existing models and pathogenic mechanisms.

3. Propose to cross diabetic mice with transgenic mice containing organ-
specific (or complication-specific) susceptibility loci.  The proposal should 
discuss the clinical relevance of both the diabetic mouse model and the 
diabetic complication.  The genetic manipulation might include standard 
transgenic knock-in or knock-out approaches, cell-specific or temporal-
specific approaches, or both.  Alternatively, the diabetic manipulation might 
be temporally specific.

4. Propose methods to extensively characterize the mice at various times for 
both diabetes and the particular diabetic complication using physiological, 
pathological, imaging, and gene-profiling methods.  Mice would be treated or 
partially treated with insulin to prevent malnutrition, wasting, and volume 
depletion and to assess the role of glycemic control on the complication.

5. Compare the mouse phenotype with data from previous human studies.

6. Use the models to find susceptibility loci and to test therapeutic, 
prevention, early detection, and imaging strategies. 

Participating NIH Institutes have briefly outlined broad areas of biomedical 
interest related to the goals of this RFA.  

NIDDK: Produce and validate mouse models of diabetic kidney disease, urinary 
tract infections, altered gastrointestinal and bladder function, and the 
diabetic foot.  Susceptibility loci might include, for example: fibrosis-
promoting genes (TGF-beta), cell-cycle control (p21), COX-2, 
renin/angiotensin system, or glomerular podocyte genes (ureteroglobin, 
nephrin).

NHLBI: Produce and validate models of macro- and micro-vessel accelerated 
atherosclerosis, peripheral vascular disease, inflammation, hypertension, 
impaired wound healing, diabetic cardiomyopathy, and abnormalities of the 
coagulation system.  Examples of susceptibility loci might include genes 
regulating lipoproteins, lipoprotein receptors and associated enzymes, 
chemotactic substances (e.g. MCP-1), adhesion molecules (e.g. VCAM), 
hemodynamic forces-affected genes, genes affecting coagulation (PAI-1), 
platelet glycoprotein receptors (IIB/IIIa), alpha2/beta1 integrins, and the 
renin/angiotensin system. 

NEI: Produce and validate mouse models of diabetic retinopathy.

NIDCR: Produce and validate mouse models of oral complications of diabetes, 
such as periodontitis, oral mucosal infections, salivary gland dysfunctions, 
and oral neuropathies.

Applicants must provide methods to maintain Unit records, establish, 
standardize, document, and distribute protocols, and provide for quality 
control and budgetary oversight.  Each Mouse Engineering and Phenotyping Unit 
will establish a database to store, organize, analyze, or visualize data 
generated by individual Units to facilitate dissemination of information and 
data-sharing within the Consortium.  Applicants must also provide methods to 
establish priorities among mouse models and to oversee the daily operation of 
Units.

It is anticipated that these proposals will be quite speculative and 
innovative, and applications may lack preliminary data on specific effects of 
a genetic manipulation on the diabetic complication or feasibility of a 
particular approach.  However, applications should include sufficient 
information to indicate that the applicant team has sufficient expertise with 
proposed techniques and that the proposed projects are feasible.

C. Data Sharing

Restricted availability of unique research resources, upon which further 
studies are dependent, can impede the advancement of research and delivery of 
medical care.  Sharing biomaterials, data, and software in a timely manner 
has been an essential element in the rapid progress that has been made in the 
genetic analyses of mammalian genomes.  NIH policy requires that 
investigators make unique research resources readily available for research 
purposes to qualified individuals within the scientific community after 
publication [NIH Grants Policy Statement 
(http://grants.nih.gov/grants/policy/nihgps, Principles and Guidelines for 
Recipients of NIH Research Grants and Contracts on Obtaining and 
Disseminating Biomedical Research Resources:  Final Notice, December 1999 
(http://www.ott.nih.gov/policy/rt_guide_final.html)].  Biomaterials (engineered 
mice) and other research resources that can be patented (e.g., phenotypic 
screens and genetic and phenotypic data for all mouse strains) produced in 
projects funded by this RFA are expected to be made available and distributed 
to the broader scientific community.

The NIH is interested in ensuring that research resources developed through 
this RFA become readily available to the research community for further 
research, development, and application, with the expectation that sharing 
will lead to products and knowledge to benefit the public.  For this reason, 
NIH is concerned that patents on mouse strains, phenotypic screens, and 
phenotypic and genetic data for all mouse strains and other research 
resources might have a chilling effect on the future development of products 
and information that may improve the public health.  At the same time, NIH 
recognizes the rights of grantees to elect and retain title to subject 
inventions developed with Federal funding under the provisions of the 
Bayh-Dole Act.

All applications are expected to include the following (see the section 
“SPECIAL INSTRUCTIONS”):

o Proposed sharing plans to insure that mice, phenotypic screens, and genetic 
and phenotypic data for all mouse strains are widely available to the 
scientific community. 

o A proposed plan addressing if, or how, the PI and grantee institution will 
exercise their intellectual property rights regarding patentable research 
resources, such as engineered mice, phenotypic screens, and phenotypic and 
genetic data for all mouse strains produced in projects funded under this 
RFA.

Applicants are encouraged to discuss proposals for addressing these 
requirements with their institutional offices of technology transfer.

D. Coordinating and Bioinformatics Unit

The Coordinating and Bioinformatics Unit will establish and maintain an 
Internet-based mechanism for rapid data and document transmission and 
electronic communication among participants in the MMDC Consortium and 
between the MMDC Consortium and the NIH.  The Unit will also establish and 
maintain a centralized and comprehensive Internet-based mouse database that 
will compile important information about mouse strains developed and studied 
by the MMDC.  These databases and web sites will serve the needs of all Units 
established by this initiative and will be an important interface between the 
MMDC Consortium and the larger research community.   Applicants should 
address data sharing, confidentiality, and security considerations. 

The Coordinating and Bioinformatics Unit will also provide travel and meeting 
support for the Steering Committee and other committees of the MMDC 
Consortium (see the section “SPECIAL INSTRUCTIONS”). 

E. Steering and Other Committees

The Principal Investigator and co-PI must be willing to be part of a Steering 
Committee that will meet twice each year together with NIH program staff to 
encourage exchange of information among investigators who participate in this 
program.  The Steering Committee may form other committees (for example, 
model validation, model phenotyping, technology) that will meet once or twice 
a year either in person or by telephone conference calls.  A major goal of 
these meetings is to facilitate progress by providing a forum for sharing 
skills, ideas, technology, data, and biological reagents.  At the meetings, 
participants will also discuss quality assurance, bioinformatics, 
coordination, and training.  If voting is necessary for an action item, NIH 
Program Scientists will share one vote. 

TERMS AND CONDITIONS OF AWARD

The following terms and conditions will be incorporated into the award 
statement and provided to the Principal Investigator(s) and to the 
institutional official at the time of award.  These special Terms of Award 
are in addition to and not in lieu of otherwise applicable OMB administrative 
guidelines, HHS Grant Administration Regulations at 45 CFR Parts 74 and 92, 
and other HHS, PHS, and NIH Grant Administration policy statements.

The administrative and funding instrument used for this program is a 
cooperative agreement (U01), an "assistance" mechanism (rather than an 
"acquisition" mechanism) in which substantial NIH scientific and/or 
programmatic involvement with the awardee is anticipated during performance 
of the activity.  Under the cooperative agreement, the NIH purpose is to 
support and/or stimulate the recipient"s activity by involvement in and 
otherwise working jointly with the award recipient in a partner role, but it 
is not to assume direction, prime responsibility, or a dominant role in the 
activity.  Consistent with this concept, the dominant role and prime 
responsibility for the activity resides with the awardees for the project as 
a whole, although specific tasks and activities to carry out the studies will 
be shared by awardees and NIH Program Scientists.

1.  Awardee Rights and Responsibilities

o The PI will have primary authority and responsibility to define objectives 
and approaches and to plan, conduct, analyze, and publish results, 
interpretations, and conclusions of studies conducted under the terms and 
conditions of the cooperative agreement award.

o The PI will assume responsibility and accountability to the applicant 
organization officials and to the NIH Institutes for the performance and 
proper conduct of the research supported by the project in accordance with 
the terms and conditions of the award.

o The PI and another senior investigator will serve as voting members of the 
Steering Committee, will attend the Planning Meeting and two Steering 
Committee meetings in the first year, and two Steering Committee meetings a 
year in subsequent years.

o The PI will be responsible for accepting and implementing the goals, 
priorities, procedures, protocols, and policies agreed upon by the Steering 
Committee and subcommittees.

o The PI will be responsible for close coordination and cooperation with the 
other components of the MMDC Consortium and with the NIH staff.

o Awardees will retain custody of, and have primary rights to, the data 
developed under these awards, subject to Government rights of access 
consistent with current HHS and NIH policies.  Investigators conducting 
biomedical research frequently develop unique research resources.  The policy 
of the PHS is to make available to the public the results and accomplishments 
of the activities that it funds.  All awardees must adhere to PHS policy for 
the distribution of unique research resources produced with PHS funding that 
was published in the NIH Guide for Grants and Contracts (NIH Guide, Vol. 25, 
No. 23, July 12, 1996), and is available at the following Internet address:   
http://grants.nih.gov/grants/guide/notice-files/not96-184.html.

o NIH reserves the right to require the transfer of appropriate mouse stocks, 
related reagents, and pertinent data that are generated as the result of 
participation in research supported under these awards to an eligible third 
party, in order to preserve the mouse models and data about them and/or to 
continue the research.  Third parties supported under these awards must be 
informed of this right.

o Effective conduct of the MMDC Consortium goals will require considerable 
electronic communication of data and other information among the MMDC 
Consortium components and between the components and the NIH.  Consortium 
members will be required to demonstrate that they have the ability to 
transfer data accurately and effectively.

o The Coordinating and Bioinformatics Unit will coordinate the logistics of 
all MMDC Consortium Steering Committee meetings, other MMDC Consortium 
committee meetings, and workshops and provide an internet-based mechanism for 
electronic communication among the MMDC Consortium components and the NIH.

2.   NIH Staff Responsibilities

NIH Program Scientists from each participating NIH institute will have 
substantial scientific-programmatic involvement during conduct of this 
activity, through technical assistance, advice and coordination above and 
beyond normal program stewardship for grants, as described below.  The 
dominant role and prime responsibility for the project as a whole resides 
with the awardees, although specific tasks and activities in carrying out the 
studies will be shared by awardees and the NIH.

The NIH will form an NIH MMDC Consortium External Coordinating Committee, 
comprised of the NIH Program Scientists and other NIH extramural staff with 
relevant scientific expertise or who manage research grant programs that 
relate scientifically to the goals of the MMDC, and outside advisors picked 
by the NIH.  The External Coordinating Committee will meet regularly to 
review the progress of the MMDC Consortium and to advise the NIH Program 
Staff of scientific developments and opportunities that may enhance the 
achievement of the MMDC Consortium goals.

o NIH Program Scientists from the participating institutes will be members of 
the Steering Committee and, as determined by that committee, its 
subcommittees.

o NIH Program Scientists will coordinate and facilitate the MMDC Consortium 
programs, attend and participate as voting members in all meetings of the 
MMDC Consortium Steering Committee, and provide liaison between the Steering 
Committee, the MMDC Consortium, and participating institutes.

o NIH Program Scientists will help the Steering Committee develop and draft 
operating policies and policies addressing recurring situations that require 
coordinated action.
 
o NIH Program Scientists will review the scientific progress of the 
individual Units, review Units for compliance with operating policies 
developed by the Steering Committee, and may recommend to the funding 
institutes to withhold support, suspend, or terminate an award for lack of 
scientific progress or failure to adhere to policies established by the 
Steering Committee.

3.  Collaborative Responsibilities

Steering Committee

The NIH Program Scientists and awardees comprising the MMDC Consortium will 
be responsible for forming a Steering Committee as defined below.  An 
arbitration system, as detailed below, will be available to resolve 
disagreements among members of the Steering Committee.  The Steering 
Committee will be the main governing board of the MMDC Consortium.  It will 
develop collaborative protocols, set priorities for model derivation, define 
parameters for model validation, identify technological impediments to 
success and strategies to overcome them, and decide when models should be 
made available to the research community for individual 
investigator-initiated projects.

o The Steering Committee will be composed of the PI and a co-PI or other 
senior investigator from each Mouse Engineering and Phenotyping Unit and the 
Coordinating and Bioinformatics Unit, and NIH Program Scientists.  The two 
investigators from each Unit will share one vote. The NIH Program Scientists 
will share one vote.  The Steering Committee will select a chairperson who 
will be someone other than an NIH staff member.

o The Steering Committee may, as it deems necessary, invite additional, 
non-voting scientific advisors to meetings at which research priorities and 
opportunities are discussed.  The NIH reserves the right to augment the 
scientific or consumer expertise of the MMDC Consortium when necessary.

o There will be two Steering Committee meetings annually, one in July in the 
Washington, DC, area and the other at a time and site agreed upon by the 
Steering Committee and the NIH.

o The first meeting of the MMDC Consortium will be a Planning Meeting in the 
Washington, DC, area soon after grants are awarded.  At the Planning Meeting, 
the Steering Committee will be formed and select a chairperson from among the 
members who represent the awardees.  At the Planning Meeting, the Steering 
Committee may: (a) draft a charter to detail policies and procedures, a 
process for monitoring compliance with the policies and procedures, and a 
process for recommending that the NIH Program Administrators act on evidence 
of non-compliance of any Consortium component with Steering Committee 
policies, (b) agree upon the terms of the charter, (c) discuss the models and 
approaches that were proposed in the project applications and any relevant 
new information, and set initial priorities for the models to be derived and 
for new technologies to be developed, (d) discuss and set initial genotypic 
and phenotypic parameters required to characterize the models and to define 
their comparability to human diabetic complications, (e) discuss and set 
initial standards for validating the models for further biological studies 
and such uses as testing prevention or early detection strategies, or 
therapies, or diagnostic imaging technologies.  At the first meeting of the 
Steering Committee following the Planning Meeting, an Internet-based 
electronic communications mechanism will be discussed and will be implemented 
by the Coordinating and Bioinformatics Unit.

o At their first meeting each year, the Steering Committee will formulate 
plans for any workshops or symposia to be held.

o At the second and subsequent meetings, the Steering Committee will refine 
the MMDC Consortium’s scientific objectives and characterization and 
validation strategies as necessary, consistent with progress in the MMDC 
Consortium components and other laboratories, and with the goals of 
identifying available models with sufficient promise for further testing, or 
defining those human diabetic complications for which models must be created 
de novo.

o At any time during the MMDC Consortium project, the Steering Committee may 
examine the characterization and validation data for models derived by the 
MMDC Consortium components and decide when a model is sufficiently validated 
that it may be distributed to the research community for further 
investigations or applications.  The NIH will provide the means to 
disseminate the mice.

o The Steering Committee will plan workshops to which non-MMDC Consortium 
participants will also be invited to (a) enable the MMDC Consortium to 
explore scientific or technologic innovation that occurs during the course of 
the project, (b) inform the research community of the progress made toward 
derivation or refinement of models or their characterization and validated 
uses, and (c) inform the research community of any technological advances 
related to design and derivation of mouse models.  The NIH Program 
Scientists, the MMDC External Coordinating Committee, and other NIH staff 
will provide the Steering Committee with advice on participants for the 
workshops and symposia.  The Coordinating and Bioinformatics Unit will manage 
the logistics for these meetings.

o The Steering Committee may establish subcommittees, as it deems 
appropriate, NIH Program Scientists and other NIH staff who are Steering 
Committee members will serve on subcommittees as they deem appropriate.

4. Arbitration

Any disagreement that may arise on scientific/programmatic matters (within 
the scope of the U01 award) between awardees and the NIH may be brought to 
arbitration.  An arbitration panel will be composed of three members:  one 
selected by the Steering Committee (with the NIH Program Scientists not 
voting) or by the individual awardee in the event of an individual 
disagreement, a second member selected by the NIH Program Scientists, and, 
the third member selected by the two prior selected members.  This special 
arbitration procedure in no way affects the awardee"s right to appeal an 
adverse action that is otherwise appealable in accordance with the PHS 
regulations at 42 CFR Part 50, Subpart D and HHS regulation at 45 CFR Part 
16.

INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS

It is the policy of the NIH that women and members of minority groups and 
their sub-populations must be included in all NIH-supported biomedical and 
behavioral research projects involving human subjects, unless a clear and 
compelling rationale and justification are provided indicating that inclusion 
is inappropriate with respect to the health of the subjects or the purpose of 
the research. This policy results from the NIH Revitalization Act of 1993 
(Section 492B of Public Law 103-43).

All investigators proposing research involving human subjects should read the 
UPDATED "NIH Guidelines for Inclusion of Women and Minorities as Subjects in 
Clinical Research," published in the NIH Guide for Grants and Contracts on 
August 2, 2000 
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-048.html), a 
complete copy of the updated Guidelines are available at:
http://grants.nih.gov/grants/funding/women_min/guidelines_update.htm. The 
revisions relate to NIH defined Phase III clinical trials and require: a) all 
applications or proposals and/or protocols to provide a description of plans 
to conduct analyses, as appropriate, to address differences by sex/gender 
and/or racial/ethnic groups, including subgroups if applicable, and b) all 
investigators to report accrual, and to conduct and report analyses, as 
appropriate, by sex/gender and/or racial/ethnic group differences.

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS

It is the policy of NIH that children (i.e., individuals under the age of 21) 
must be included in all human subjects research, conducted or supported by 
the NIH, unless there are scientific and ethical reasons not to include them. 
This policy applies to all initial (Type 1) applications submitted for 
receipt dates after October 1, 1998.

All investigators proposing research involving human subjects should read the 
"NIH Policy and Guidelines" on the Inclusion of Children as Participants in 
Research Involving Human Subjects that was published in the NIH Guide for 
Grants and Contracts, March 6, 1998, and is available at the following URL 
address: http://grants.nih.gov/grants/guide/notice-files/not98-024.html
Investigators also may obtain copies of these policies from the program staff 
listed under INQUIRIES. Program staff may also provide additional relevant 
information concerning the policy.

URLS IN NIH GRANT APPLICATIONS OR APPENDICES

All applications and proposals for NIH funding must be self-contained within 
specified page limitations. Unless otherwise specified in an NIH 
solicitation, internet addresses (URLs) should not be used to provide 
information necessary to the review because reviewers are under no obligation 
to view the Internet sites. Reviewers are cautioned that their anonymity may 
be compromised when they directly access an Internet site.

LETTER OF INTENT

Prospective applicants are asked to submit by February 28, 2001, a Letter of 
Intent that includes a descriptive title of the proposed research, name, 
address, and telephone number of the Principal Investigator, identities of 
other key personnel and participating institutions, and the number and title 
of the RFA in response to which the application may be submitted. Although a 
letter of intent is not required, is not binding, and does not enter into the 
review of subsequent applications, the information allows NIDDK staff to 
estimate the potential review workload and to plan the review. The Letter of 
Intent is to be sent to:

Chief, Review Branch 
Division of Extramural Activities, NIDDK
6707 Democracy Boulevard, Room 653 MSC 5452
Bethesda, MD 20892-5452
Bethesda, MD 20817 (for express/courier service)
Tel:  (301) 594-8885
Fax:  (301) 480-3505

APPLICATION PROCEDURES

The research grant application form PHS 398 (rev. 4/98) is to be used in 
applying for these awards, with the modified format that is described below. 
These forms are available at most institutional offices of sponsored 
research, from GrantsInfo, Division of Extramural Outreach and Information 
Resources, National Institutes of Health, 6701 Rockledge Drive, Suite 6095, 
Bethesda, MD 20892-7910, telephone 301-435-0714, email: GrantsInfo@nih.gov.

The RFA label available in the PHS 398 (rev. 4/98) application form must be 
affixed to the bottom of the face page of the application.  Failure to use 
this label could result in delayed processing of the application such that it 
may not reach the review committee in time for review.  In addition, the RFA 
title and number must be typed on line 2a of the face page of the application 
form and the YES box must be marked.

The sample RFA label available at: 
http://grants.nih.gov/grants/funding/phs398/label-bk.pdf has been modified to 
allow for this change. Please note this is in PDF format.  Submit a signed, 
typewritten original of the application, including the Checklist, and three 
signed photocopies, in one package to:

Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040 MSC-7710
Bethesda, MD  20892-7710
Bethesda MD 20817 (for express/courier service)

At the time of submission, two additional copies of the application must also 
be sent to:

Chief, Review Branch 
Division of Extramural Activities, NIDDK
6707 Democracy Boulevard, Room 653 MSC 5452
Bethesda, MD 20892-5452
Bethesda, MD 20817 (for express/courier service)
Tel:  (301) 594-8885

Applications must be received by March 28, 2001.  If an application is 
received after that date, it will be returned to the applicant without 
review.  

The Center for Scientific Review (CSR) will not accept any application in 
response to this announcement that is essentially the same as one currently 
pending initial review, unless the applicant withdraws the pending 
application.  The CSR will not accept any application that is essentially the 
same as one already reviewed.  This does not preclude the submission of a 
substantial revision of an application already reviewed, but such an 
application must follow the guidance in the PHS Form 398 application 
instructions for the preparation of revised applications, including an 
introduction addressing the previous critique.

SPECIAL INSTRUCTIONS

Applicants may apply for a Mouse Engineering and Phenotyping Unit, a 
Coordinating and Bioinformatics Unit, or both.  If an applicant applies for 
both, separate applications must be submitted.

1.  General Application Format Instructions

The form PHS 398 should be modified as follows. Biosketches and "Other 
Support" pages should be included for all personnel.  The number of pages 
allowed for the "Research Plan" is increased from 25 to 40 pages for the 
Mouse Engineering and Phenotyping Units, but remains at 25 pages for the 
Coordinating and Bioinformatics Unit.  Budget pages, budget justifications, 
material transfer agreements, and letters from collaborators and consultants 
and their biosketches are not included in this limit. 

2. Applications for Mouse Engineering and Phenotyping Units

Applicants for the Mouse Engineering and Phenotyping Units should divide the 
"Research Plan" into the sections indicated below. 

Part 1. Infrastructure.  In this part of the "Research Plan," applicants 
should detail the specialized or unique facilities, fundamental 
infrastructure, research expertise, and core resources and services that are 
available to support the planned mouse model derivation, characterization, 
and validation.  If facilities at more than one institution are required, 
applicants should thoroughly describe them and obtain appropriate assurances.  
Methods for mouse, data, and information flow and sharing within the Unit 
should be described.  Applicants should discuss their barrier facilities, 
requirements for importing non-SPF animals, and where the phenotyping will be 
performed (behind a barrier or in a regular laboratory). The location of any 
imaging equipment should be specified (i.e., is the imaging equipment in a 
barrier facility?).  The roles and expertise of all key personnel, 
collaborators, and consultants who are associated with this part of the 
application should be well documented. Applicants must also provide methods 
for establishing priorities among mouse models.  An internal advisory board 
consisting of the Principal and co-Investigators and other important 
personnel should oversee the daily operation of the Unit.  Applicants should 
describe how the Unit will fit into, augment, and be supported by the parent 
institution and plan for designating an alternate or replacement Principal 
Investigator should it become necessary.

Part 2. Model Derivation.  In this part of the "Research Plan," applicants 
should discuss the clinical relevance of both the diabetic mouse model and 
the diabetic complication.  Applicants should discuss their rationale for the 
design and derivation of a new mouse model or models, or for altering and 
improving an existing model or models, based on their experience with mouse 
models of human disease and their knowledge of basic, translational, and 
clinical diabetes research.  Applicants should describe the extent to which 
they plan to characterize any models they derive or refine, the methods that 
they will use to characterize the models, the rationale for choices of 
methods, and how generally applicable the methods are, or will be, for all 
mouse diabetes and diabetes complication models.  In this part as well, 
applicants are expected to identify the standards they will apply to validate 
a model or models, the rationale for the choices, how generally applicable 
the validation standards are, or will be, for all mouse diabetes or diabetes 
complication models, and, the purpose(s) for which they anticipate their 
models may be used.  Applicants should describe their barrier facility, 
requirements to bring non-SPF animals into their institution, and the 
location of the phenotyping Unit relative to the barrier.  The roles and 
expertise of all key personnel, collaborators, and consultants who are 
associated with this part of the application should be thoroughly documented. 

Part 3. Technology.  In this part of the "Research Plan," applicants should 
define the technologic approaches they will use, or any technology that they 
propose to develop, to achieve the goals of model derivation or refinement, 
characterization, and validation.  The roles and expertise of all key 
personnel, collaborators, and consultants who are associated with this part 
of the application should be thoroughly documented.

Part 4. Interactions with Other MMDC Consortium Components and the Research 
Community.  In this part of the "Research Plan," applicants must include 
specific plans for responding to the "Terms and Conditions of Award" section. 
Applicants should state their willingness to collaborate and share data 
freely with the other MMDC Consortium components and the wider research 
community.  Applicants must include a data sharing plan, a mouse sharing 
plan, and copies of all Material Transfer Agreements and Mouse Transfer 
Agreements used by all institutions involved in the application.  Applicants 
are encouraged to use the NIH Simple Letter of Agreement to transfer 
materials, available at http://www.ott.nih.gov/policy/rt_guide_final.html#guide. 
Applicants should discuss their willingness to serve on the Steering 
Committee and other Consortium committees and should state their willingness 
to follow the common protocols that will be developed by the Steering 
Committee, particularly those that relate to setting priorities for model 
development and the standards for characterization and validation.  
Applicants must state their willingness to plan and attend workshops and 
symposia.

Applicants should describe how their unique blend of experience can 
contribute to the collective efforts of the MMDC Consortium.  Applicants 
should also describe how they will comply with the involvement of NIH Program 
Scientists and fulfill the responsibilities of Consortium components to work 
together cooperatively.  Applicants should describe their experience with, 
and capability for, Internet-based communication and ideas for facilitating 
electronic communication and other interactions among the MMDC Consortium 
components, NIH, and the general research community.

The scientific review group will evaluate the adequacy of the proposed plan 
for sharing and data access.  Comments on the plan and any concerns will be 
presented in an administrative note in the summary statement.  The adequacy 
of the plan will be considered by NIH program staff and will be important in 
determining whether the grant shall be awarded.  The sharing plan(s) as 
approved, after negotiation with the applicant when necessary, will be a 
condition of the award.  Evaluation of non-competing continuation 
applications will include assessment of the effectiveness of research 
resource release.

Applicants are reminded that the grantee institution is required to disclose 
each subject invention to NIH within two months after the inventor discloses 
it in writing to grantee institutional personnel responsible for patent 
matters.  The awarding Institute reserves the right to monitor awardee 
activity in this area to ascertain if patents or patent applications on mice 
identified through phenotypic screens, phenotypic screens, and phenotypic and 
genotypic data for all mouse strains or other patentable subject matter are 
adversely affecting the goals of this RFA.

3. Applications for the Coordinating and Bioinformatics Unit

Applicants for the Coordinating and Bioinformatics Unit should discuss 
Infrastructure, Technology, and Interactions, as described above.  Part 2 
above should be omitted. This narrative should include, for example:

Part 1. Infrastructure. Applicants should discuss the administrative 
structure of the coordinating Unit and plans for providing administrative 
support for up to five meetings a year. 

Part 3. Technology. Applicants should describe the Internet-based mechanism 
for rapid electronic communication among participants and the NIH, the 
structure of the centralized and comprehensive database, and web sites for 
communication within the MMDC consortium and with the research community. 
Applicants should describe issues of data validity, security, and 
confidentiality.

Part 4. Interactions with other MMDC Components and the Research Community. 
Applicants should discuss data sharing and willingness to participate in 
common activities, committees, and workshops as outlined in Part 4 above. 
Applicants must include a data sharing plan and copies of the Material 
Transfer Agreements used by all institutions in the proposal.

4. Budget Instructions

Applicants who have additional funds to support (‘leverage’) the application 
should indicate the source of funds (institutional, R01, P01, P30, etc.) that 
permit them to accomplish the project goals.  Subcontract budgets should be a 
separate page, and the subcontract indirect costs should be calculated and 
listed in the usual place as part of the direct costs of the budget.  
However, only direct costs associated with each subcontract will count toward 
the direct costs cap of $500,000 on the budget for the first year. 

Specific budget issues related to cooperative agreements must also be 
addressed as follows.

o Applicants must budget for travel and per diem expenses for participation 
in the MMDC Consortium Steering Committee, subcommittees, workshops, and 
symposia.  Applicants should budget for seven trips to the Bethesda, MD, area 
each year.

o Applicants for the Coordinating and Bioinformatics Unit should include 
travel support for 15 additional outside consultants to attend Steering and 
other committees meetings and workshops in the Bethesda, MD, area each year.

REVIEW CONSIDERATIONS

General Considerations

All applications will be judged on the basis of the scientific merit of the 
proposed project and the documented ability of the investigators to meet the 
RESEARCH OBJECTIVES of the RFA.  Although the technical merit of the proposed 
protocol is important, it will not be the sole criterion for evaluation of a 
study.  Other factors considered to be important for review include 
demonstrated expertise in mouse genetic engineering and phenotyping as 
applied to the design and derivation of mouse models of human disease, a 
multi-disciplinary team of collaborators, substantial interactions among 
collaborating researchers, demonstration of appropriate facilities and 
resources, willingness to share data and reagents freely.

Supplemental information of up to three pages will be allowed if received by 
May 1, 2001.  Send materials to Chief, Review Branch, at the address above. 

Review Method

Upon receipt, applications will be reviewed for completeness by the CSR and 
responsiveness by the NIDDK.  Incomplete applications will be returned to the 
applicant without further consideration.  

Applications that are complete and responsive to the RFA will be evaluated 
for scientific and technical merit by an appropriate peer review group 
convened by the NIDDK in accordance with the review criteria stated below.  
As part of the initial merit review, all applications will receive a written 
critique and undergo a process in which only those applications deemed to 
have the highest scientific merit, generally the top half of the applications 
under review, will be discussed, assigned a priority score, and receive a 
second level review by the National Diabetes and Digestive and Kidney 
Diseases Advisory Council, the National Heart, Lung, and Blood Advisory 
Council, the National Eye Advisory Council, and the National Dental and 
Craniofacial Research Advisory Council.

Review Criteria

Applicants are encouraged to submit and describe their own ideas about how 
best to meet the goals of the cooperative study and their specific protocols, 
and they are expected to address issues identified under ”TERMS AND 
CONDITIONS OF AWARD” and ”SPECIAL INSTRUCTIONS’ sections of the RFA.  The 
peer review group will assess the scientific merit of the applications and 
related factors using the following criteria:

1. Innovation.  Does the project employ novel concepts, approaches or method?  
Is the project original and innovative?  Does the project challenge existing 
paradigms or develop new methodologies or technologies?  Will the approaches 
advance the field of mouse or other model development?

2.  Approach.  Are the conceptual framework, design, methods, and analyses 
adequately developed and appropriate to the aims of the project?  Does the 
applicant acknowledge potential problem areas and consider alternative 
tactics? Can these approaches be used to derive mouse models of diabetic 
complications in addition to those proposed?  Are the parameters chosen to 
characterize the model(s) sufficient and appropriate?  Are these parameters 
generally applicable to all mouse diabetic complication models?  Are the 
standards chosen to validate the model(s) for its relevance to a human 
diabetic complication or for testing therapy, prevention, early detection, or 
imaging appropriate and adequate?

3.  Significance.  Do the model or models proposed for derivation/ 
characterization/validation address an important need for the diabetic 
complication research community?  What is the immediacy of the research 
opportunity?  Over the project period, is there potential for the group to 
develop models other than those specified in the application?

4.  Investigators.  Are the principal investigator and his/her collaborators 
appropriately trained and well suited to carry out this work?  To what extent 
do these investigators have the necessary complementary skills?  Have 
collaborations been established or consultants identified to provide the 
appropriate depth and breadth of scientific expertise required for the 
project?  Will this team of investigators contribute unique skills to the 
overall Consortium?

5.  Environment.  Are the facilities for mouse maintenance and 
experimentation appropriate to support the endeavor?  Does the scientific 
environment in which the work will be done contribute to the probability of 
success?  Do the proposed experiments take advantage of unique features of 
the scientific environment and incorporate the best use of collaborative 
arrangements?  Is there evidence of institutional support? If advanced 
imaging techniques are proposed, is the instrument located behind an animal 
barrier?

Additional Considerations

6.  Interactions.  Are there adequate plans for effective interaction and 
coordination among Consortium components and the NIH?  Are the proposed plans 
to share data and mice adequate? Do the investigators state their willingness 
to collaborate extensively and share information fully?  Are the Material 
Transfer Agreements and Mouse Transfer Agreements straightforward?  Do the 
investigators state their willingness to abide by the priorities and policies 
agreed upon by the Steering Committee?  Have the applicants proposed sound 
strategies for communication among themselves, with the other MMDC 
components, and with the NIH?

7.  Budget.  Assess the appropriateness of the proposed budget and duration 
in relation to the proposed research. Does the budget for fundamental 
infrastructure, model development, characterization and validation, and 
technology development indicate that the applicants understand the 
requirements of managing this sort of model-building enterprise? 

8. Coordinating and Bioinformatics Unit. Does the Unit employ novel concepts, 
approaches or methods? Are the principal investigator and collaborators 
appropriately trained and well suited to provide support for multiple 
investigative teams and to design and implement internet-based Web sites and 
databases? Are the computer facilities (hardware, software, and personnel) 
sufficient to support the endeavor?  Are there adequate plans for providing 
meeting support, Internet-based communication, databases, and web sites for 
use by the MMDC Consortium?  Have the applicants addressed data sharing 
policies, confidentiality issues, and security considerations?  Are there 
adequate plans for open access to these databases and web sites by the 
general research community?

AWARD CRITERIA

The intent of this RFA is to enable the NIDDK to assemble a Consortium of 
highly qualified Units of investigators whose complementary scientific skills 
and expertise will enable them to achieve the goal of deriving validated 
mouse models that are analogous to human diabetic complications.  The NIDDK 
will choose Units for the Consortium that will collectively provide the most 
creative approaches to mouse model design, and have a range of research 
focus, experience, technology, and resources to ensure that a range of models 
of diabetic complications are rapidly derived and validated.

Applications recommended by the NIH Advisory Councils will be considered for 
award based upon (a) scientific and technical merit as determined by peer 
review, (b) the importance of the proposed models for research in diabetic 
complications, (c) the degree of originality and innovation in model design, 
(d) the creativity of the approaches and technologies for model derivation, 
characterization, and validation, (e) the likelihood for substantial 
contribution by the applicants to a successful collaborative MMDC, (f) the 
evidence for willingness to work cooperatively, (g) the quality and 
availability of animal research infrastructure and resources, (h) program 
balance, including, in this instance, sufficient compatibility of features to 
make a successful collaborative program a reasonable likelihood, and (i) the 
availability of funds.

Schedule
Public Information Meeting:       December 2000
Letter of Intent Receipt Date:    February 28, 2001
Application Receipt Date:         March 28, 2001
Peer Review Date:                 June-August 2001
Council Review:                   September 2001
Earliest Anticipated Start Date:  September 30, 2001

INQUIRIES

A public information meeting will be held in December 2000 in Bethesda, 
Maryland.  The date and time of this meeting, answers to frequently asked 
questions, and other updates about this RFA will be posted on the NIDDK Web 
site (or http://www.niddk.nih.gov/fund/crfo/highlights.htm) as they are 
developed.  Applicants are highly encouraged to visit this Web site regularly 
in the course of preparing applications.  Potential applicants are encouraged 
to subscribe to the MMDC Discussion List at list.nih.gov/archives/mmdc-l.html
. These sites will contain the most current information available.

Written and telephone inquiries concerning this RFA are encouraged.  The 
opportunity to clarify any issues or questions from potential applicants is 
welcome.  Direct inquiries regarding programmatic issues that are not 
addressed at the website to:

Robert A. Star, M.D.
Division of Kidney, Urologic, and Hematologic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases
31 Center Drive, Room 9A35
Bethesda, MD 20892-2560
Tel:  (301) 594-7717
Fax: (301) 496-2830
E-mail: Robert_Star@nih.gov

Momtaz Wassef, Ph.D.
Atherosclerosis Research Group
Division of Heart and Vascular Diseases
National Heart, Lung, and Blood Institute
Rockledge 2, Room 10193Bethesda, MD 20892-7956
Tel: (301) 435-0550
Fax:(301) 480-2858
E-mail: Wassefm@NIH.gov

Nancy L. Nadon, Ph.D.
Head, Office of Biological Resources and Resource Development
National Institute on Aging
7201 Wisconsin Ave./ GW 2C231
Bethesda, MD 20892
Tel: (301) 496-6402 
Fax: (301) 402-0010
E-mail: nadonn@exmur.nia.nih.gov 

Dennis F. Mangan, Ph.D.
Infectious Diseases and Immunity Branch
Division of Extramural Research
National Institute of Dental and Craniofacial Research
45 Center Drive, Room 4AN-32F
Bethesda, MD 20892-6402
Tel: (301) 594-2421
Fax: (301) 480-8318
E-mail: Dennis.Mangan@nih.gov

Direct inquiries regarding fiscal matters to:

Teresa Farris
Division of Extramural Activities 
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 630 MSC 5456
Bethesda, MD 20892-5456
Tel:  (301) 594-7682
Fax: (301) 480-3504
E-mail: FarrisT@extra.niddk.nih.gov

Ms. Jane R. Davis
Grants Operations Branch
Division of Extramural Affairs
National Heart, Lung, and Blood Institute
Rockledge 2, Room 7174
Bethesda, MD 20892-7926
Tel: (301) 435-0149?
Fax: (301) 480-3310
E-mail: Davisj@NIH.Gov

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance No. 
93.121, 93.837, 93.847, 93.848, and 93.849.  Awards are made under 
authorization of the Public Health Service Act, Title IV, Part A (Public Law 
78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered 
under NIH grants policies and Federal Regulations 42 CFR 52 and 45 CFR Parts 
74 and 92.  This program is not subject to the intergovernmental review 
requirements of Executive Order 12372 or Health Systems Agency review.

The PHS strongly encourages all grant and contract recipients to provide a 
smoke-free workplace and promote the non-use of all tobacco products.  In 
addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking 
in certain facilities (or in some cases, any portion of a facility) in which 
regular or routine education, library, day care, health care or early 
childhood development services are provided to children.  This is consistent 
with the PHS mission to protect and advance the physical and mental health of 
the American people.



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