**November 9, 2007 CSR Integrated Biological II Open House Breakout
Groups**

**Report Out Summary**

The substantive focus of the November 9, 2007 CSR Integrated Biological
II Open House was the breakout groups. These groups provided a forum for
external participants to respond to two science-focused questions. Each
breakout group was led by a Study Section chair and a Professional
Society representative who co-facilitated the group as two Scientific
Review Officers (SROs) recorded the discussion. At the conclusion of
each breakout group session, participants reconvened in the auditorium,
where each group reported the top consensus issues listed below.
Post-meeting comments regarding these report-out issues can be e-mailed
to <CSRIB2oh@csr.nih.gov>. The post-meeting comment period will close on
December 17, 2007.

**Question 1:**

**What will be the most important questions and/or enabling technologies
you see forthcoming within the science of your discipline in the next 10
years?**

**Cellular, Molecular, and Developmental Mechanisms I**

1.  Overlap in areas of research, e.g., inflammation is involved in a
    wide range of diseases (either as a cause or response), including
    many diseases of aging including cancer, heart, brain, muscle,
    autoimmune.

2.  Integrate clinical, biochemical, mathematical and physiological and
    database sharing and analysis, e.g., toxicology/pharmacology to
    forefront, cell biology, and glycobiology. Integrative approaches to
    interdisciplinary areas of science, e.g., neuroimmunoendocrine
    interactions, aging/obesity/diabetes/cardiology, oxidative stress
    and inflammation, respiratory, cardiovascular and aging.

3.  Functional consequences of genetics and epigenetics in biology and
    disease.

4.  Integration of multiple models and humans is appropriate, e.g.,
    mouse, but also the continued use of higher or lower organisms.

5.  Technology:

    A.  in vivo functional/dynamic imaging/sensing in real time in cells
        and animals/humans, e.g., nanotechnology/bioengineering.

    B.  High-throughput chemical screens, new ways to perform multiplex
        chemical/small molecule screens, plus the emergence of
        high-content screens. It will be challenging to identify the
        likeliest most significant output to date, and be as certain as
        possible of not supporting the simple collection of datastreams
        with limited relevance.

    C.  New proteomic approaches.

    D.  Sequencing; histone code/epigenetics and chromatin structure;
        post-translation proteolytic regulation; proteomic analysis and
        protein sequencing data.

    E.  Classical molecular biology approaches will continue to be
        needed.

    F.  Epigenetics at single cell and real-time resolution.

6.  *Data bases*: proteomics; genomics; systems biology

    A.  Team approaches will increase.

    B.  Developmental biology: availability of data on web;
        user-friendly formats will continue to be invented, with biology
        at the forefront, and training of "interface" scientists needed.

    C.  Computational mathematical modeling, engineering/physical
        sciences will be important; functional meta-analysis of enormous
        amounts of data already collected.

7.  *Immunology*:

    A.  Animal Models -- mouse vs. non-human primates.

    B.  Understanding mechanism of genomic instability in hematopoiesis;
        identify causes for susceptibility to disease.

8.  Glycobiology will increase in importance, e.g., how ECM works, etc.

9.  Move to examination of complex cellular environments (e.g., biofilm
    biology).

10. Stem cell biology and induction of regeneration, especially with
    respect to understanding the epigenetic coding of gene regulation.

11. Developmental toxicology, pharmacology and birth defects in
    mammalian models.

12. Biosensor development to monitor cellular and tissue processes in
    vivo in a variety of model organisms, ultimately leading towards
    mammals, primates and humans.

13. Genetics in the traditionally exploitable organisms such as
    Drosophila will continue to be important as we move forward into the
    fundamental exploration of the complex area of for example,
    glycobiology.

14. There will be a focus on integrated studies of organogenesis and
    morphogenesis. High-quality, high-precision descriptive data will be
    generated and there will be a substantial need to identify the key
    reviewers, or train new ones, who are capable of recognizing the
    highest impact, highest significant amongst these types of
    applications.

15. Cross-training of individuals who will be able to conduct research
    in and converse in as well as review grant applications that involve
    various divergent disciplines and biological topics and
    math/engineering.

**Cellular, Molecular, and Developmental Mechanisms II**

1.  Studies on stem cells are rapidly expanding into different areas.
    Either new study sections need to be created or expertise is needed
    across study sections to adsorb this in the context development and
    regeneration as this may become a dominant theme in multiple
    disciplines.

2.  Integrative or systems biological approaches on complex biological
    systems (e.g., the brain and the immune system) are emerging
    including *in vivo* functional imaging, computational biology,
    bioinformatics and high throughput technology. There is concern that
    these approaches are reliably looking at function. Need more
    emphasis on how to analyze complex data sets. There is a need for
    interdisciplinary approaches, mechanisms through which different
    disciplines communicate with each other, and an NIH mechanism to
    foster multiple approaches. There is also concern about emphasis on
    detail versus looking at systems. A systems appreciation is needed
    for groups to review cross-discipline research. Examples of emerging
    areas for study include human, whole organ, integrative signaling
    networks, systems level, as well as cellular and organelle
    functions.

3.  Need for more animal models? There is a need for more or different
    technologies to develop better (e.g., other regulated in vivo
    inducible systems in addition to Cre-lox), more useful, and relevant
    model systems for evaluation. The movement is presently toward, for
    example, inducible versus transgenic mouse model systems. There is a
    need for expertise in these evolving new systems. There is also a
    need for more documentation and database sharing availability on the
    web, i.e., a central place for this information about the quality of
    already available mouse model systems. In addition, aging and gender
    need to have greater consideration (e.g., cardiovascular systems) in
    the development of these systems.

4.  Epigenetics, functional genomics, and proteomics are emerging areas,
    including studies on gene function and regulation or pathways
    analysis. There is a need for centers so that individual
    investigators do not have to invest in these changing technologies.
    The alternative is to form collaborations with persons with these
    expertise.

5.  Nonotechnology and bioengineering (ex vivo and in vivo approaches)
    are also emerging areas. Do these require separate study sections or
    should they be integrated into existing study sections? It was noted
    that these were developed by chemists, but there is a need for input
    from biologists and toxicologists (e.g., drug delivery).

6.  Translational science and technology training. Need for workshops
    and continuing education for training to keep basic scientists up to
    date with in depth understanding of these new technologies, like
    sabbaticals, CME.

7.  Integrated signal transduction -- need for understanding these broad
    based pathways as they become more complex -- need a way to present
    this in a way for better understanding of these "Krebs cycle" --like
    complexities.

**Clinical**

1.  Use of genetics, imaging, biomarkers and behavior to formulate
    non-invasive predictors for early stages of diseases and responses
    to treatment. Increase precision of diagnoses to detect early stages
    of disease to facilitate risk stratification and improve patient
    oriented outcomes.

2.  Understanding the effects of inactivity, aging, and sleep disorders
    on mechanisms and bioepidemiology of chronic disease, for example,
    obesity, diabetes, cardiovascular disease.

3.  Need for computational skills to handle enormous amounts of data.
    Involve [bio]{.underline}-statisticians in early stage of design.
    Include clinically relevant assessment.

4.  Need for state-of-the-art technologies and flexibility of design in
    clinical trials, including those in regenerative medicine. Serve as
    platform to ask other scientific questions.

5.  Need to understand interactions at all levels, e.g., cells, organs,
    individuals, conditions, health care systems, etc., to facilitate
    integration across different areas.

6.  Deal with barriers to research, e.g., management of consent process,
    emergency room, large data bases, and diversity inclusion.

**Preclinical and Translational Research**

1.  Develop preclinical and translational tools from many sources --
    proteomics, genomics, biomarkers, statistical analysis paradigms,
    systems biology approaches to clinical practice, making it more
    likely animal model research will be more predictive of clinical
    efficacy, outcomes, and disease prevention. Science to do this does
    not exist.

2.  Development of preclinical and translational enabling technologies,
    including imaging (static and functional, improving temporal and
    special resolution), nanotechnology, high throughput screening,
    better quantitative measures, drug discovery.

3.  Overarching studies of problems such as impact of obesity,
    inflammation and aging on multiple organ systems at all stages of
    life, focusing both on prevention and treatment.

> **Question 2:**

**Is the science of your discipline, in its present state, appropriately
evaluated within the current study section alignment? Suggestions?**

**Cellular, Molecular, and Developmental Mechanisms I**

1.  *Recruiting Best Reviewers*: Better incentives, "points" for Study
    Section service, applicants need to be taught how to:

    A.  Provide suggests for reviewers in specific expertise/topic
        areas, while maintaining the review confidentiality barrier.

    B.  Target their application to the most appropriate study section.

    C.  Write their application in any shortened format to identify in
        the most concise and coherent manner the significance of the
        questions being approached or addressed.

2.  *Multidisciplinary Research: Systems analysis and integrative
    analytical approaches are not the same -- care will be needed in
    defining these terms.*

> Need generalists to bridge, as well as specialists for
> multidisciplinary research review; dual assignment in Study Sections.
>
> With respect to collaborative/multi-investigator research, the middle
> author position, currently seen by some to be taken as a disadvantage,
> needs to be re-evaluated within the context of it identifying an
> unusually strong scientific collaborative arrangement.

3.  *Scoring:* Especially with respect to streamlined/unscored
    applications, make the raw preliminary scores available to the
    applicant as a way of indicating any disparate levels of enthusiasm,
    or the "degree to which it was unscored"; indicate whether an
    application was discussed. It is important than an unscored
    applicant know whether the application was unscored because it was
    just barely below the cut off point or a poor application.

4.  *Study Section Uniformity*: Guidelines regarding the review process
    need to be uniformly applied across study sections R01, R21 & R03s.
    For example, reviewers should not require preliminary data for an
    application mechanism that does not require preliminary data.

5.  *Adding and Removing Study Sections:*

    A.  Alcohol, Immunology and Toxicology have no home.

    B.  Need Study Sections between CMAD and ASG.

    C.  Exercise physiology is not appropriately reviewed when combined
        with vascular biology and cardiac hypertrophy.

6.  Non-Hypothesis/Discovery Driven Grants: There needs to be a
    considerable degree of retraining of study section evaluators to
    ensure fairness and a valued review of descriptive and technology
    driven applications.

**Cellular, Molecular and Developmental Mechanisms II**

1.  The current SRG alignment does not permit crossing alignment
    boundaries, e.g., alcohol. There is only one study section for that
    area and it is a poor fit. Need for cross-disciplinary study
    sections. Need mechanism-cross study sections, rather than disease.

2.  Need for more Study Sections if applications received in any area
    are greater than an optimal number, or some areas are not covered by
    current study sections.

3.  Tissue or organ related aging applications are not well covered.
    Some corresponding new Study Sections may be needed. For example, in
    aging, there are two SRGs that review these areas now. Need a new
    one focused on tissues, e.g., heart, lung. The muscle SRG now does
    not address aging well.

4.  The published descriptions of some of the study sections need to be
    updated to more appropriately reflect the areas being reviewed. For
    example, the Electrical Signaling, Transport and Arrhythmia (ESTA)
    Study Section guidelines need to broaden so that electrophysiology
    and arrhythmias falls better within the scope and purview of the
    study section.

5.  Regeneration medicine area is covered in diverse study sections. A
    Study Section for cardiovascular stem cells and regeneration
    medicine may be needed.

6.  There is concern about the review of orphan diseases and how CSR
    deals with areas that do not receive grants in a certain area
    because the people are not getting funded in that area. CSR and the
    NIH should be sensitive to these still important areas (e.g., Staph
    aureus and MERSA).

7.  *Some Process Issues:*

    A.  Difficulty to the evaluate significance of applications dealing
        with studies in established and rapidly growing areas.

    B.  *Format of Review Meetings*: Telephone reviewers are not good
        for Study Section meeting. Other alternative reviews were not
        impressive.

    C.  *Quality of Reviewers:* Training of new reviewers needs to be
        enhanced. Ad hoc service is good for training and Web-based
        training may be developed. Possible training by institution.

**Clinical**

1.  K awards not reviewed well in some Institutes/Study Sections; should
    be put in K award Study Sections with specific expertise.

2.  Multidisciplinary applications: (1) fragmented expertise in study
    sections not conducive to consistent review; (2) difficult to know
    where to direct for review. Maybe reviewed by standing ad hoc panel?

3.  Not enough integrated expertise within study sections for some
    areas, e.g., alcohol/toxicology, exercise/integrative systems,
    physiology. Sometimes applications in these areas given inadequate
    review.

4.  Clinical trials: not consistent appropriate Study Sections for
    review. Need discussion between Institutes and CSR.

5.  Need flexibility in time of service for reviewers with expertise
    hard to find.

6.  Not clear how willing scientists get involved as reviewers.

**Preclinical and Translational Research**

1.  Studies of fundamental human biology that are not clinical trials
    sometimes have problems finding an adequate review.

2.  Review process works well for in depth studies, but when we come to
    multidisciplinary applications it is more of a problem.

3.  General concern for new investigator reviews in all disciplines.

**Conclusion**

The Center for Scientific Review will carefully review these comments
and suggestions and will consider appropriate steps to address concerns.
For example, CSR plans to address the challenges facing review of
translational and multidisciplinary applications. To ensure stakeholder
participation and broad perspective, results from Open House
deliberation will be presented to the NIH Peer Review Advisory Committee
(PRAC) for its consideration before changes are implemented.

Center for Scientific Review

National Institutes of Health

U.S. Department of Health and Human Services

December 4, 2007