NIDDK BIOTECHNOLOGY CENTERS

Release Date:  October 30, 2000

RFA:  DK-01-019

National Institute of Diabetes and Digestive and Kidney Diseases

Letter of Intent Receipt Date:  December 22, 2000
Application Receipt Date:       January 19, 2001

PURPOSE

The purpose of this RFA is to make comprehensive gene expression technologies 
widely available to researchers working in areas supported by NIDDK.  This 
RFA seeks to establish Biotechnology Centers that will provide genomic 
profiling resources to investigators working in research areas within the 
NIDDK’s mission. 

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 nonprofit 
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 for this 
solicitation.  Racial/ethnic minority individuals, women, and persons with 
disabilities are encouraged to apply as Principal Investigators.

MECHANISM OF SUPPORT

This RFA will use the NIH grant-in-aid resource-related mechanism grant (R24) 
award.  Except as otherwise stated in this announcement, awards will be 
administered as stated in the NIH Grants Policy Statement.

This RFA is a one-time solicitation.  The total requested project period for 
an application submitted in response to this RFA may not exceed three years.  
The maximum dollar request is limited to $350,000 of direct costs for each 
budget year.  It is anticipated that the budget for the second and third 
years will provide for pilot and feasibility studies of future projects using 
this technology.  Responsibility for the planning, direction, and execution 
of the proposed project will be solely that of the applicant.  The 
anticipated award date is July 1, 2001.

FUNDS AVAILABLE

For FY 2001, $3 million will be committed to fund applications submitted in 
response to this RFA.  It is anticipated that about six Biotechnology Centers 
will be funded; however, this funding level is dependent upon the receipt of 
a sufficient number of applications of high scientific merit.  Although this 
program is provided for in the financial plans of the NIDDK, the award of 
grants pursuant to this RFA is also contingent upon the availability of funds 
for this purpose.

RESEARCH OBJECTIVES

A. Background

The tremendous acceleration in pace of scientific discovery over the last 
decade, coupled with development of many new high-throughput technologies, 
has created an era of unparalleled opportunity to uncover the causes of 
disease and identify effective therapies.  In particular, the Human Genome 
Project and related efforts to identify at least some unique pieces of all 
expressed genes (expressed sequence tags, ESTs) in the human genome has 
resulted in an explosion of data and potential tools that will aid research 
in virtually all fields of medicine. The recent development of genome-wide 
expression profiling (chip or microarray) allows a comprehensive high-
throughput screening of the effects of an insult (genetic, physiologic, 
pathologic, etc.) on gene expression in tissues and specific cell populations 
of interest.  These techniques may aid in determining the function of a gene 
or discovering new biomarkers and therapeutics for patients with disease. 
Many investigators with hypothesis-driven research programs want access to 
these emerging technologies.  Cost is a major obstacle to the application of 
these techniques by large numbers of investigators.  The investment required 
to obtain essential equipment and personnel to establish this technology is 
more than can easily be borne by a single investigator.

B. Objectives and Scope

This RFA is intended to support the cost-effective introduction of techniques 
to measure patterns of gene expression in specific tissues of interest to the 
NIDDK-supported investigators.  This RFA will allow the formation of support 
facilities that may include, but are not limited to:

1. cDNA Microarrays.  The applicant might propose to print, read, and analyze 
microarrays.  The arrays might contain mixtures of cDNAs obtained from 
commercial vendors, the Cancer Genome Anatomy Project (CGAP), or ESTs 
obtained locally and of specific interest to the investigators.  It is 
anticipated that each printing unit will distribute arrays to 7 to 20 NIDDK 
investigators. Applicants are expected to identify the sources of the cDNAs, 
reference all genes to a genomic database (Entrez, Unigene, Locus Link, 
etc.), and indicate plans to distribute arrays to the NIDDK community at a 
reasonable cost.  Applicants need not include budgets for equipment for 
printing or reading arrays or for bioinformatics support if they can obtain 
the necessary reagents or support from collaborative efforts or commercial 
sources.

2. Oligonucleotide Chips.  The applicant might propose to produce, hybridize, 
read, and/or analyze gene chips from commercial or academic sources.  
Applicants are expected to discuss the source and composition of the chips, 
and details of the bioinformatic support. 

Creation and maintenance of these technologies may require the collaboration 
of investigators with expertise in many fields, such as molecular biology, 
robotics, bioinformatics, genomics, and statistics.  In addition, key aspects 
of infrastructure may also be supported and might include the development and 
maintenance of appropriate databases and specialized equipment.  It is 
important to emphasize that there are a variety of approaches to genome-wide 
expression analysis.  Therefore, a given strategy must be rigorously 
justified and must demonstrate that all key personnel are involved in the 
formulation of the rationale and approach.

An objective of this RFA is to provide biotechnology support for both on-
going and new hypothesis-driven research projects. Therefore, applicants will 
be required to describe projects that will benefit from these technologies.

C. Annual Meetings

The Principal Investigator must be willing to be part of a Steering Committee 
consisting of representatives of each Biotechnology Center.  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, bioinformatics, coordination, and 
training.
	 
D. Sharing Data and Biological Materials in Human Genetic Research

Timely sharing of information, materials, and technology will speed 
scientific discovery by permitting researchers access to sufficiently large 
and well-characterized resources as quickly as possible.  This sharing of 
materials and data, including those that have not yet or may never be 
published, is essential to rapid progress and will help to avoid unnecessary 
duplication of large data collections. 

It is recognized that time may be required to verify the accuracy of data, to 
perform initial analyses, and to protect intellectual property rights to 
ensure that inventions, including therapeutic agents, are pursued and 
developed rapidly for the benefit of the public.  Thus, a protected period, 
from the time data and materials are collected to the time they are made 
available to other qualified investigators, may be appropriate.  The onset 
and duration of the period will vary, depending upon the nature of the 
research project.  Applicants must justify the length of the protected 
period.

Where appropriate, grantees may work with the private sector to make unique 
resources available to the larger biomedical research community at a 
reasonable cost. Applicants may request funds to defray the costs of sharing 
materials or submitting data, with adequate justification. 

E. Post-Award Management
 
During the course of the grant period, technologies will improve, genomic 
technologies will evolve, and the rate of progress and focus of work 
supported by the grant(s) may change.  It is expected that the Principal 
Investigator(s), after consultation with NIDDK program staff, will make any 
necessary adjustment in scientific direction to accommodate the changing 
environment.  

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 December 22, 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
Democracy 2, Room 655
6707 Democracy Blvd MSC 5452
Bethesda, MD 20892-5452
Telephone: (301) 594-8897
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 your 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
Democracy 2, Room 655
6707 Democracy Blvd MSC 5452
Bethesda, MD 20817-5452
Telephone: (301) 594-8897
FAX: (301) 480-3505

Applications must be received by January 19, 2001.  If an application is 
received after that 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

The applicants must carefully justify methodologies, technologies, 
bioinformatics, statistical analytical tools, and costs, and describe the 
limitations of the approaches. Genome-wide expression analysis is a rapidly 
evolving field. Hence, applicants must discuss how they will be poised to 
take advantage of technical and methodological advances and their impact on 
the throughput and costs proposed.

The application should clearly identify both source and number of clones to 
be arrayed, hybridization and standardization protocols, quality control both 
of RNA and fabricated arrays, signal detection and quantitation.   Particular 
attention should be given to biostatistical and bioinformatics issues in both 
experimental design and data analysis.

Scientific Application to Hypothesis-Driven Research Projects: Applicants 
must include descriptions of five to ten ongoing representative projects that 
will use the gene profiling technology.  Applicants must also include 
descriptions of several pilot and feasibility studies for new projects that 
will use this technology.  These projects should be proposed for budget years 
2 and 3.  Each project description should be approximately one page in length 
and be included in the Experimental Design and Methods portion of the 
application.  Project descriptions should include a rationale for application 
of array technology to the experimental problem.  Experimental details should 
include the tissue sources, time course, number of replicates and expected 
results.  The study section will consider the appropriateness of the data 
analysis plan including statistics and data interpretation and prioritization 
for follow-up studies.

Training and Education: Currently, only a few NIDDK-supported investigators 
are in a position to use genomic technologies.  To address this deficiency, 
each application must include plans to establish training and education 
programs.  These programs should train local investigators to use these 
techniques.  In addition, the applicants should indicate their willingness to 
provide service and training to the larger NIDDK community.  The methods and 
procedures for selecting qualified individuals and the duration and types of 
service or training should be delineated in the application.

Internal Advisory Committee: The application must describe the composition 
and functions of an internal advisory committee that would meet to discuss, 
for example, quality control, prioritization of resources, funding of pilot 
projects in the second and third years, training, sharing of reagents and 
experimental data, and adaptation to changing technologies. 

Annual Meetings: 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.  
Applications should include a statement indicating willingness to participate 
in these meetings.

Sharing of Data and Biological Materials: In order to ensure the timely 
sharing of information and materials, applicants will be requested to 
describe in detail how, when, and in what manner data, materials, and 
technology will be made available to the scientific community.  In addition, 
the applicant should outline how the rights and interests of the participants 
in genetic research will be assured.

Applicants should discuss any pre-existing intellectual property rights, 
including options to for-profit research sponsors, who might be associated 
with the clones, sequences, and experimental results that may be generated.

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 may 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.

Review Criteria

The goals of NIH-supported research are to advance our understanding of 
biological systems, improve the control of disease, and enhance health.  In 
the written comments, reviewer will be asked to discuss the following aspects 
of the application in order to judge the likelihood that the proposed 
research will have a substantial impact on the pursuit of these goals.  Each 
of these criteria will be addressed and considered in assigning the overall 
score, weighting them as appropriate for each application.  Note that the 
application does not need to be strong in all categories to be judged likely 
to have major scientific impact and thus deserve a high priority score.  For 
example, an investigator may propose to carry out important work that by its 
nature is not innovative but is essential to move a field forward.

o Approach: Will the technology resources significantly improve progress made 
by the projects.  Are the conceptual framework, design, methods, and analysis 
adequately developed, well-integrated, and appropriate to the aims of the 
projects?  Does the applicant acknowledge potential problem areas and 
consider alternative tactics? Are the applicant’s plans for quality control 
of all materials adequate?  Is the biostatistics and bioinformatics support 
adequate?  Is the applicant willing and able to participate actively in a 
collaborative program?  Will the applicant share resources and release data 
in a timely manner, and will they train and educate other investigators in 
the use of these data and materials?

o Innovation: Do the 5-10 representative projects employ novel concepts, 
approaches, or methods?  Do the projects challenge existing paradigms or 
develop new methodologies or technologies?  Are the 2-3 new pilot and 
feasibility studies innovative?

o Investigator: Are the investigators appropriately trained and well suited 
to carry out this work?  Is the work proposed appropriate to the experience 
level of the investigators?

o Significance: Do the scientific projects address important problems? If the 
aims of the application are achieved, how will scientific knowledge be 
advanced?  What will be the effect of these studies on the concepts or 
methods that drive the fields?

o Environment: Does the scientific environment in which the work will be done 
contribute to the probability of success?  Do the proposed technologies take 
advantage of unique features of the scientific environment or employ useful 
collaborative arrangements?  Is there evidence of institutional support?

The initial review group will also be asked to examine how the scientific 
projects will benefit from the new technologies, and how this will further 
NIDDK programmatic interests.

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

o Adequacy of plans to include both genders, minorities and their subgroups, 
and children as appropriate for the scientific goals of the research. Plans 
for the recruitment and retention of subjects will also be evaluated.

o The reasonableness of the proposed budget and duration to the proposed 
research.

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.

AWARD CRITERIA

The anticipated date of award is July 1, 2001.

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

o Scientific merit as determined by peer review;

o Availability of funds;

o Programmatic priorities, including program relevance of the hypothesis-
driven scientific projects that will be aided by the advanced technology;

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.  Applicants are 
encouraged to review the NIDDK website for updates or responses to frequently 
asked questions at http://www.niddk.nih.gov/fund/crfo/highlights.htm#biotech.

Direct inquiries regarding programmatic issues 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 MSC 2560
Bethesda, MD 20892-2560
Telephone: (301) 594-7715
FAX: (301) 496-2830
E-mail: Robert_Star@nih.gov

Philip F. Smith, Ph.D.
Division of Diabetes, Endocrinology, and Metabolic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Blvd RM 693 MSC5460
Bethesda MD 20892-5460
Telephone: (301) 594-8816
FAX: (301) 480-3503
E-mail:	ps56z@nih.gov

Jose Serrano, M.D., Ph.D.
Division of Digestive Diseases and Nutrition
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Blvd RM 671 MSC5450
Bethesda MD 20892-5450
phone:	(301) 594-8871
FAX: (301) 480-8300
E-mail:SerranoJ@extra.niddk.nih.gov

Direct inquiries regarding fiscal and administrative matters to:

Donna Huggins
Division of Extramural Activities 
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Blvd RM 637 MSC5456
Bethesda, MD 20892-5456
Telephone: (301) 594-8848 
FAX: 301-480-3504
E-mail: HugginsD@extra.niddk.nih.gov

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance No. 
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 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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