MOUSE METABOLIC PHENOTYPING CENTERS FOR MODELS OF DIABETES AND ITS COMPLICATIONS

Release Date:  February 8, 2000

RFA:  DK-00-014 (This RFA has been renewed, see RFA-DK-05-008)

National Institute of Diabetes and Digestive and Kidney Diseases

Letter of Intent Receipt Date:  June 12, 2000
Application Receipt Date:       July 12, 2000

PURPOSE

This Request for Applications (RFA) solicits applications to establish 
national centers for the purpose of detailed metabolic phenotyping of 
knock-out mice and other mouse models potentially useful for 
understanding diabetes, its complications, obesity and related 
metabolic diseases or conditions.  These facilities are expected to 
provide a range of standardized procedures to characterize metabolism, 
body composition, feeding behavior, activity, tissue pathology, and 
other physiologic, anatomic or pathological alterations that may occur 
in these mice. The user group for these centers is expected to be NIH 
grantees and others, both inside and outside the institution, who wish 
to submit their various mice for detailed metabolic and physiologic 
phenotyping beyond what would be possible or cost-effective in their 
individual laboratories.  Because the mice to be characterized will 
have been developed on a variety of genetic backgrounds, 
characterization must be applicable to the major mouse strains used for 
research.  Applicants should propose plans to prioritize use of the 
facility and for cost recovery from users.  Coordination among the 
Mouse Metabolic Phenotyping Centers established in response to this RFA 
will be required.  Finally, Centers are expected to develop improved 
methods to characterize the mice using a Pilot and Feasibility Project 
mechanism.

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 
Metabolic Phenotyping Centers for Models of Diabetes and Its 
Complications), is related to the priority area of Diabetes and Chronic 
Disabling Conditions.  Potential applicants may obtain a copy of 
"Healthy People 2010" at http://odphp.osophs.dhhs.gov/pubs/hp2000

ELIGIBILITY REQUIREMENTS

Applications may be submitted by domestic for-profit and nonprofit 
organizations, public and private, such as universities, colleges, 
hospitals, units of State and Local governments, and eligible agencies 
of the Federal government.  Foreign institutions are not eligible, 
although they may apply for Pilot and Feasibility funds from the Mouse 
Metabolic Phenotyping Centers.  Racial/ethnic minority individuals, 
women, and persons with disabilities are encouraged to apply as 
principal investigators.

MECHANISM OF SUPPORT

This RFA will use the National Institutes of Health (NIH) cooperative 
agreement (U24) award mechanism.  The cooperative agreement is used 
when participation by NIH staff is warranted to support and/or 
stimulate the recipients' activities by working jointly with the award 
recipients as a partner.  However, NIH staff will not assume prime 
responsibility or take a dominant role in the activity.  Details of the 
responsibilities, relationships, and governance of the studies funded 
under cooperative agreements are discussed below in "Terms and 
Conditions of Award" under SPECIAL REQUIREMENTS.  Except as otherwise 
stated in this announcement, awards will be administered under National 
Institutes of Health (NIH) grants policy as stated in the NIH Grants 
Policy Statement.

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 March 1, 2001.

FUNDS AVAILABLE

The NIDDK intends to commit approximately $3,000,000 in FY 2001 to fund 
up to 4 new cooperative agreements in response to this RFA.  An 
applicant may request a project period of up to 5 years and a budget 
for direct costs of up to $750,000 per year.  Budget requests should 
make explicit the anticipated operating costs including fees charged to 
users for services.  Because the nature and scope of the proposed 
research may vary, it is anticipated that the size of the awards will 
also vary.  Although the financial plans of the NIDDK provide support 
for this program, awards pursuant to this RFA are contingent upon the 
availability of funds and the receipt of a sufficient number of 
applications of outstanding scientific and technical merit.  At this 
time, it is not known if this RFA will be reissued.

RESEARCH OBJECTIVES

Background

Mutant mouse models, generated either by directed knock-out or 
transgenic techniques or by large-scale mutagenesis, are important 
tools for understanding the role of specific genes in health and 
disease. Genetic factors are thought to underlie the initiation, 
progression, and severity of complex diseases of interest to NIDDK: 
diabetes, obesity, and the devastating micro- and macrovascular 
complications of diabetes, such as nephropathy, neuropathy, 
retinopathy, and atherosclerosis.  These diseases have proven difficult 
to study, partly due to lack of very good animal models and partly due 
to the complexity of the problem.  Good animal models may allow for 
more rapid development and assessment of therapies and preventive 
measures.  Candidate genes for diabetes and related disorders are being 
identified and mutated in directed research projects.  These new mice 
include animals containing multiple altered genes or genes altered in 
specific tissues.  Heterozygous knock-out mice are also potentially 
useful models for complex metabolic disease.  New large-scale 
mutagenesis programs are expected to generate animal models of complex 
metabolic diseases in addition to other disorders.

The resultant mice from both these approaches may have subtle 
phenotypes that could be particularly difficult to detect with simple 
high throughput tests, or with data taken at a single time point.  
Defects may be exposed only in the presence of physiologic or 
nutritional stress.  Moreover, simple genetic manipulations could 
result in a very complex phenotype due to minor alterations in a large 
number of pathways and organs, or in their interaction.  The types of 
experiments that are currently available to study metabolic processes--
glucose and insulin clamps, indirect calorimetry, or organ balance, 
PET, NMR and other tracer studies--are very difficult to do in tiny 
animals, and require specialized equipment and expertise.  
Characterization of diabetic complications via measurement of 
glomerular filtration rate, cardiac or renal hemodynamics also become 
technically challenging when done in mice.  Therefore, researchers 
would benefit from a few centralized, well-equipped facilities to which 
they could submit their mice for detailed phenotyping.

Objectives and Scope

A national Mouse Metabolic Phenotyping Center must be an identifiable 
unit within a single institution such as a university, or a consortium 
of cooperating institutions including an affiliated university.  An 
existing program of excellence in biomedical research in the area of 
diabetes or diabetes complications would be considered a strength.  The 
center would be available to study mice generated by NIH-funded and 
other investigators from both outside and inside the institution.  

In general, Centers will be comprised of several components.  Examples 
include a phenotyping laboratory and analysis core, an animal care 
core, a research and development program, and an administrative core.  
In addition, a Center may house an informatics core, a modeling 
project, or other cores deemed necessary.  It is hoped that Centers 
will play a leadership role in the standardization of currently 
available phenotyping tests and in the development of new technologies.  
Centers are encouraged to propose a Pilot and Feasibility program 
capable of supporting small research projects within and outside the 
parent institution for the development of new technologies.  

The Centers funded by this RFA will be expected to interact with each 
other to maximize and coordinate service to the diabetes research 
community.  A National Steering Committee comprised of funded principal 
investigators, NIH staff, and external advisors will be established in 
order to oversee and coordinate the funded Centers, and it is expected 
to meet about once a year.  Applicants should propose a description of 
this body and its duties.

A more thorough description of possible cores follows.

A. Phenotyping Laboratory And Analysis Cores

Centers will design or adapt and standardize a variety of tests that 
can be conducted on living animals or on body fluids and tissue 
samples.  These tests would constitute a metabolic phenotyping 'exam' 
for potential mouse models of diabetes, diabetic complications, obesity 
and complex metabolic diseases.  Emphasis will be placed on 
technologies that study live animals, although Centers may accept 
tissue samples (pancreas, kidney, heart, liver, fat) or body fluids 
(blood, plasma, urine) as well as whole live animals from users for 
phenotyping.  Centers may choose to provide either standard or 
customized 'exams' for various animal models, and should propose a 
method to advise users in order to determine the appropriate series of 
tests.  Phenotyping tests may be designed to identify: 1) metabolic, 
signaling or endocrine alterations that result in altered glucose 
metabolism, obesity or feeding behavior, insulin resistance, 
dyslipidemia, diabetes, or other metabolic diseases; 2) altered 
susceptibility to or progression of diabetes, obesity, etc.; 3) defects 
in hormone production, secretion, receptor recognition, or 
intracellular action; 4) developmental alterations leading to diabetes, 
alterations in severity of diabetic complications, obesity, or other 
metabolic disorders; or 5) susceptibility to the sequelae of diabetes 
such as nephropathy, macrovascular disease, retinopathy, or neuropathy.  
In addition, a series of high-throughput tests may be proposed to 
identify other possible disease models of interest to NIDDK.

Applicants must carefully justify methodologies, technologies, 
statistical analytical tools, and costs, and describe the limitations 
of the approaches.  Applicants must indicate the number of tests that 
can be performed each year.  Potentially interesting mice will have 
been developed on a variety of genetic backgrounds.  Therefore 
characterization must be applicable to the major mouse strains used for 
research.  Centers will be required to establish 'normal' parameters 
for each test on the appropriate wild type background strains.  A 
quality control method for establishing, maintaining, and documenting 
the reliability of all tests should be proposed.

Many of the proposed tests are likely to require significant 
development and standardization during the funding period.  A detailed 
plan for such development should be included in the application.  
Applicants are encouraged to work with members of other communities, 
specifically researchers that already have important techniques used in 
rats, in order to miniaturize or otherwise adapt these extant 
techniques for use in mice.

Each funded center will have unique strengths, either because of the 
technologies available to it, or because of expertise in some aspect of 
metabolism, diabetes, diabetic complications, etc.  It is expected that 
each center will work closely with the others through a National 
Steering Committee to take full advantage of these strengths and 
provide the best possible range of tests.  Ongoing research to provide 
new tests, with an emphasis on novel technologies and miniaturization, 
should also be coordinated through this body.

Examples of phenotyping tests include, but are not limited to:

o Glucose and insulin clamps;

o  Carbon-13 NMR studies of metabolic pathway flux;

o  PET or other imaging measurements of regional nutrient uptake;

o  Whole body or organ balance tracer measurements of carbohydrate, 
protein, amino acid, or lipid uptake and production;

o  Body composition measurements;

o  Appetite, food intake, whole body energy balance and activity 
measurements;

o  Glomerular filtration rate, proteinuria, and renal hemodynamics;

o  Exercise stress testing;

o  Physiologic measurements, such as blood pressure, cardiac output, 
regional blood flow, or nerve function;

o  Anatomy and tissue pathology;

o  Hormone, cytokine, metabolite, ion, enzyme profiles in very small 
volumes of body fluids;

o  Physiologic and/or metabolic response to exogenous hormones or 
altered diet;

o  Alterations in development;

o  Immune parameters, especially those that are significant for 
development of type 1 diabetes and diabetic complications; or

o  Vulnerability of tissues to complications of diabetes.

B. Animal Care Core

Investigators will receive, house, feed, monitor and maintain the 
health of submitted mice for the duration required for the phenotyping 
exam.  Proposals must include policies, procedures, and anticipated 
costs for these items.  It is not anticipated that these animals will 
be returned to the users.

C. Research and Development Core

This RFA aims to foster the development of new technologies and tests 
that will enhance and enlarge the capability of the centers to 
characterize mouse models of diabetes, obesity and metabolic disorders, 
and diabetic complications.  This might include, for example, novel 
technologies applied to living animals, miniaturization of existing 
assays, or contracting or collaborating with investigators from other 
areas to lend their expertise to develop new technologies or assays.  A 
detailed plan for these projects should be submitted in the 
application.  In addition to in-house research and development efforts 
that would take place under the auspices of the principal or co-
investigators, the Centers are encouraged to propose a Pilot and 
Feasibility program.  This would provide short-term grant support (1-2 
years) to fund projects in new technology and test development and 
would provide a mechanism to draw upon technologies yet to be developed 
or expertise not found within the Center.  Centers would be expected to 
dedicate at least $150,000 of direct costs during years 2-5 for these 
projects, which would be solicited from inside and outside the 
institution.  This money would be competitively distributed to 1) 
develop new technologies or miniaturization of existing technologies 
for use in mice; 2) develop applications of existing technologies for 
mouse phenotyping; 3) provide new tests to meet identifiable, 
outstanding needs of the Center(s); 4) establish new types of 
mathematical models, informatics, databases or products that otherwise 
augment the Centers.  These funds are not intended to support ongoing 
funded research of an investigator.  They would in most cases not be 
renewable.  Applications may contain examples of the sorts of Pilot and 
Feasibility projects that might be solicited.  These might outline 
goals, experimental approach, and the difficulties that would need to 
be overcome, but they need not be fully developed.  

Each Center will be required to administer a finite portfolio of Pilot 
and Feasibility Projects, which will likely be a subset of those 
selected under the auspices of the National Steering Committee.  These 
will be funded through the parent U24 awards as subcontracts to outside 
institutions, or as subprojects within the parent institution.   It is 
expected that the Pilot and Feasibility programs will be overseen by 
the National Steering Committee, which will work with the NIH and all 
funded Centers to determine the appropriate methods for national 
solicitation, selection, and administration of these awards.  The U24 
application should propose methods by which these will be accomplished.  

D. Administrative Core

Applicants must provide methods to maintain center records, establish, 
standardize, document and distribute protocols, and to provide for 
quality control and budgetary oversight.  Applicants must also provide 
methods for establishing priorities among submitted mice, and a plan 
for full or partial cost recovery from users.  The same priority 
criteria and reimbursement structure should be applied to submitted 
animals from all investigators, whether inside or outside the parent 
institution.  Applicants should plan to advise users on the appropriate 
'exam' for their particular animal model and research goals.  They must 
plan to distribute funds for Pilot and Feasibility projects, and inform 
the research community of the available phenotyping exams.  An internal 
advisory board consisting of the principal and co-investigators and 
other important personnel should be proposed in order to oversee the 
daily operation of the center.  The Applicant should describe how the 
center 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.

E. Databases and Data Sharing

Timely sharing of information, materials, protocols and technology will 
speed scientific discovery by permitting researchers access to 
well-characterized resources as quickly as possible.  At the same time, 
data collected on submitted mouse models cannot be considered public 
information.  Applicants are expected to propose appropriate means of 
recording data and interacting with the research community.   They 
should comment regarding the confidentiality of data collected on 
submitted mouse models.  It is hoped that databases, web sites, etc. 
will be able to serve the needs of all centers established by this 
initiative.  

SPECIAL REQUIREMENTS 

Applicants must indicate their willingness to be part of a National 
Steering Committee consisting of representatives of each Phenotyping 
Center, NIH staff, and members of the scientific community who are 
unaffiliated with funded centers, and who will act in an advisory 
capacity.  The annual meetings will be held to encourage exchange of 
information among investigators who participate in this program.  A 
major goal of these meetings is to facilitate progress by providing a 
forum that will lead to sharing skills, ideas, technology, data, and 
biological reagents.  At the meetings, participants will also discuss 
quality assurance, informatics, coordination, sharing, means of 
informing the research community of services offered by the Phenotyping 
Centers, and training.  Applicants must indicate their willingness to 
work together to develop a range of phenotyping tests that are 
complimentary.  If duplication is absolutely necessary, centers should 
expect to use similar protocols.  The National Steering Committee will 
also participate in administering the Pilot and Feasibility arms of the 
Centers.  Applicants must include travel funds that will allow the 
Principal Investigator and at least one other key research scientist to 
participate each year for a one-day meeting in Bethesda, Maryland.

During the course of the funding period, technologies will improve, and 
the rate of progress and focus of work supported by the cooperative 
agreement may change.  It is expected that the Principal 
Investigator(s), in consultation with NIDDK program staff and the 
National Steering Committee, will make any 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.

TERMS AND CONDITIONS OF AWARD
 
The administrative and funding instrument used for the Centers is a 
cooperative agreement (U24), an "assistance" mechanism in which 
substantial NIH scientific and programmatic involvement with the 
awardee is anticipated during the performance of the agreement.
 
Under the cooperative agreement, NIDDK's purpose is to work with the 
Center as a partner to assist and stimulate the Centers' planning and 
implementation.  NIDDK will not assume primary direction, 
responsibility, or a dominant operating role in the Center.  The 
primary role and total responsibility for Center programs resides with 
each Center.  The Center and the NIDDK as noted below will share 
specific tasks and activities in completing the agreement.
 
These special Terms of Award are in addition to and not in lieu of 
otherwise applicable U.S. Office of Management and Budget 
administrative guidelines, HHS Grant Administration Regulations at 45 
CFR Parts 74 and 92, and other HHS and NIH Grant Administration 
policies.
 
1.  Awardee Rights and Responsibilities
 
The Awardee will have primary and lead responsibilities for the project 
as a whole, but is expected to collaborate and cooperate with the 
National Steering Committee, as well as with NIDDK staff.  The Awardee 
is expected to administer the Center, design and provide mouse 
phenotyping tests for the diabetes and metabolic diseases research 
community, and facilitate and support research as outlined in the 
application.
 
The Awardee will establish an Internal Advisory Committee to provide 
scientific and administrative oversight.  The Advisory Committee will 
be composed of the lead center personnel, and other technical or 
research personnel.  These individuals are not limited to center 
faculty.  The committee is expected to meet at least monthly.  Minutes 
of these meetings will be made available to NIH staff upon request.
 
The Advisory Committee is charged with both prioritizing projects 
submitted to the Center and periodically reviewing Center activities to 
ensure that Center objectives, as outlined in the application, are 
being met.

Data on normal mouse background strains shall become public and 
available.  The users will retain custody of, and have primary rights 
to, the data taken on their particular mouse models, subject to 
Government rights of access consistent with current HHS and NIH 
policies.  These data may be made public with permission of the 
investigator to whom the animals belong.
 
2.  NIH Staff Responsibilities
 
The NIDDK Program Officer will have substantial scientific and 
programmatic involvement in the Centers.  NIDDK will designate a 
Program Officer and a Grants Management Specialist to provide 
administrative oversight of the cooperative agreement.  The NIDDK and 
the awardees will jointly select members of the National Steering 
Committee.  The NIDDK Program Officer will assist the awardees in 
coordinating activities among the Centers, providing information to 
researchers about the availability of services, and in developing 
policies for prioritization of use of these services.

3.  Collaborative Responsibilities
 
A National Steering Committee, composed of the principal investigators 
of each supported Metabolic Phenotyping Center, the NIDDK Program 
Officer, and external advisors, has the primary responsibility for 
developing and implementing common procedures, guidelines, and criteria 
across Centers.  It will also be responsible for establishing common 
procedures and guidelines for Pilot and Feasibility programs, and for 
reviewing submitted applications.  The Mouse Metabolic Phenotyping 
Centers agree to use any common guidelines and procedures set by the 
National Steering Committee (e.g., process for systematic review of 
quality control, protocols, record keeping, database management, report 
formats).
 
4.  Arbitration
 
Any disagreement that may arise on scientific and programmatic matters 
within the scope of the cooperative agreement and between award 
recipients and NIDDK may be brought to arbitration.  An arbitration 
panel will be composed of three members: one selected by the Center 
Principal Investigator; a second member selected by NIDDK; and, the 
third member selected by the two prior selected members.  This special 
arbitration procedure in no way effects the awardee's right to appeal 
an adverse action that is appealable in accordance with PHS regulations 
at 42 CFR Part 50, Subpart D, and HHS regulation at 45 CFR Part 16.

LETTER OF INTENT 

Prospective applicants are asked to submit by June 12, 2000 a letter of 
intent that includes a descriptive title of the proposed research; the 
name, address, and telephone number of the Principal Investigator; the 
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 a subsequent application, the information 
that it contains allows NIDDK staff to estimate the potential review 
workload and avoid conflict of interest in the review.

The letter of intent is to be sent to:

Chief, Review Branch 
Division of Extramural Activities, NIDDK
Room 653
6707 Democracy Boulevard MSC 5452
Bethesda, MD 20892-5452 
(Bethesda, MD 20817 for express/courier service)
Telephone:  (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 grants.  These forms are available at most 
institutional offices of sponsored research and may be obtained from 
the Division of Extramural Outreach and Information Resources, National 
Institutes of Health, 6701 Rockledge Drive, MSC 7910, 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 2 
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 time of submission, two additional copies of the application must be 
sent to:

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

Applications must be received by July 12, 2000.  If an application is 
received after this date, it will be returned to the applicant without 
review.  Supplemental documents containing significant revision or 
additions will not be accepted, unless applicants are notified by the 
Scientific Review Administrator.  

The Center for Scientific Review (CSR) will not accept any application 
in response to this RFA 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 substantial revisions of applications previously 
reviewed, but such applications must include an introduction addressing 
the previous critique.

SPECIAL INSTRUCTIONS TO APPLICANTS

Applicants must carefully describe methodologies, technologies, quality 
control measures, record keeping, statistical tools, costs and cost 
recovery strategies, and known limitations of proposed tests.  
Applicants should outline strategies for research and development of 
new tests, or implementation of tests that will take place during the 
funded period.  Since new techniques are being developed rapidly, the 
applicant should discuss how they will take advantage of technical and 
methodological advances as they occur.

Pilot and Feasibility Program:  Applicants may include brief 
descriptions of sample Pilot and Feasibility studies to demonstrate the 
sort of projects likely to be solicited.  Applicants should outline 
strategies for solicitation and review of Pilot and Feasibility 
applications, and for administering awards.  It is expected that all 
awarded Centers will work with NIH, each other, and the National 
Steering Committee to finalize and implement policies regarding the 
Pilot and Feasibility programs. Each Center will be required to 
administer a subset of awarded Pilot and Feasibility Projects, either 
as subcontracts under the parent U24 award to other institutions, or as 
subprojects within the parent institution.

Internal Advisory Committee:  The application should describe the 
composition and functions of an Internal Advisory Committee that would 
establish priorities for the Center, discuss issues of quality control, 
cost recovery, record keeping, new technologies, etc. 

National Steering Committee:  One external National Steering Committee 
will be established to oversee all funded Centers.  Applicants should 
propose strategies for staffing this committee, and an outline of its 
duties.

Annual Meetings:  Applicants must include travel funds that will allow 
the Principal Investigator and at least one other key person to 
participate each year in a one-day meeting in Bethesda, Maryland.  
Applications should include a statement indicating willingness to 
participate in these meetings.  

REVIEW CONSIDERATIONS

Upon receipt, applications will be reviewed for completeness by the CSR 
and responsiveness by the NIDDK.  Incomplete and/or non-responsive 
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.

Applications for Mouse Metabolic Phenotyping Centers will be reviewed 
in the context of their ability to support and expand NIDDK's goals to 
study and treat diabetes and its complications, obesity, and other 
complex metabolic diseases.  Specific review criteria are:

o Proposed Phenotyping Tests: Will the proposed tests characterize a 
reasonable range of metabolic phenomena, and provide information that 
would otherwise be unavailable to most laboratories, or more cost-
effective to conduct centrally?  Do they utilize state-of-the-art 
technology?  Is the necessary technical and analytical expertise 
available?  Will the proposed tests help researchers characterize 
existing mouse models of disease and identify new ones? 

o Innovation: Does the application demonstrate potential for in-house 
development of important new tests and technologies that will expand 
the scope and quality of the available phenotyping exam?  In addition, 
does it indicate a willingness to participate in a Pilot and 
Feasibility program that would also contribute new tests and 
technologies to the Center?  Are adequate mechanisms proposed for 
collecting and reviewing applications and administering funds for this 
program?

o Coordination:  Is the applicant willing and able to provide a 
phenotyping service for the national diabetes, metabolism, and NIDDK 
research communities?  Does the applicant state a willingness to work 
with the NIH, other awarded Centers and a National Steering Committee 
to develop the best possible set of phenotyping tests?  Will this 
service be accessible to outside investigators, and are the criteria 
for prioritizing the testing of submitted mice fair and equitable?  Is 
the applicant willing to share protocols and technology with the 
research public?  Is the applicant willing to participate in developing 
a national database of test results on control animals from appropriate 
background strains, and other appropriate information? 

o Management:  Are the applicant’s plans for oversight, animal care, 
quality control and record-keeping adequate?   

o  Investigators:  Are the investigators appropriately trained and well 
suited to carry out this work?  Do they have experience with metabolic 
research, with mice, and with the proposed technologies?  Is the 
proposed work appropriate to the experience level of the principal 
investigator and other researchers? 

o  Resources and Environment:  Does the institutional environment in 
which the work will be done contribute to the probability of success?  
Is there evidence of institutional support?  Are there appropriate 
facilities and equipment, and will the Center have access to them?  Is 
there an intellectual research community available to participate in 
test development?  Are there candidate users at the applicant 
institution?

In addition to the above criteria, in accordance with NIH policy, all 
applications will also be reviewed with respect to the following:

o  The reasonableness of the proposed budget.

o  The adequacy of the proposed protection of humans, animals, or the 
environment, to the extent that they may be adversely affected by the 
project proposed in the application.

Schedule
Letter of Intent Receipt Date:    June 12, 2000
Application Receipt Date:         July 12, 2000
Peer Review Date:                 November-December, 2000
Council Review:                   January, 2001
Earliest Anticipated Start Date:  March 1, 2001

AWARD CRITERIA

Award criteria that will be used to make award decisions include:

o Merit of the proposed service and scientific projects as determined 
by peer review;

o Programmatic priorities, including geographic location of the 
applicant organization, diversity of phenotyping tests, willingness to 
work with other institutions to minimize overlap between centers, and 
relevance of the phenotyping tests to advance the understanding of 
diabetes and diabetic complications;

o Availability of funds; and

o Total cost of the project.


INQUIRIES

Inquiries concerning this RFA are encouraged.  The opportunity to 
clarify any issues or questions from potential applicants is welcome.

Direct inquiries regarding programmatic issues to:

Maren R. Laughlin, Ph.D. 
Division of Diabetes, Endocrinology and Metabolic Diseases
NIDDK   45/5AN-24J
45 Center Drive MSC 6600
Bethesda, MD 20892-6600
Telephone:  (301) 594-8802
FAX:  (301) 480-3503
E-mail:  maren.laughlin@nih.gov

Robert A. Star, M.D.
Division of Kidney, Urologic, and Hematologic Diseases 
NIDDK  45/6AS-13K
45 Center Drive MSC 6600
Bethesda, MD 20892-6600
Telephone:  (301) 594-7715
FAX: (301) 480-3510
E-mail:  StarR@extra.niddk.nih.gov

Direct inquiries regarding fiscal matters to:

Mary Kay Rosenberg
Division of Extramural Activities 
NIDDK  45/6AS-49D
45 Center Drive MSC 6600
Bethesda, MD 20892-6600
Telephone:  (301) 594-8891 
FAX: (301) 480-3504
E-mail:  RosenbergM@extra.niddk.nih.gov

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance 
No. 93.93.847, 93.848 and 93.849.  Awards are 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 NIH 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 NIH mission to 
protect and advance the physical and mental health of the American 
people.

Weekly TOC for this Announcement
NIH Funding Opportunities and Notices

	Office of Extramural Research (OER)			National Institutes of Health (NIH) 9000 Rockville Pike Bethesda, Maryland 20892			Department of Health and Human Services (HHS)
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