Summary and Recommendations
of the CSR Advisory Committee
Working Group on Skeletal Muscle Biology

March 15 - 17, 2001

The Muscle Biology Working Group considered principles of how best to structure the review of skeletal muscle biology research and whether there should be a special "home" for the review of these applications. It was noted that skeletal muscle applications are currently distributed across at least six study sections and that this had been viewed as a chronic concern that might have stifled the growth of the field. In particular, it was remarked that applications dealing with the muscular dystrophies have no single group of scientists reviewing them. Secondary to these considerations was the impact that removal of skeletal muscle applications from existing study sections would have.

Some discussion centered on the possibility that current review mechanisms were adequate and therefore nothing needs to be fixed. However, there was enough sentiment and fact to persuade the group that skeletal muscle biology applications would be more appropriately reviewed in a focused study section.

One model for structuring such a review group was to divide it into normal and diseased muscle. However, that idea was ultimately rejected because it is important to provide expertise on normal function and disease within one review panel. Another suggestion was to focus on separate biological processes, but it was felt that this would result in too many areas and a lack of focus. Some discussion also centered on whether methodology should be an organizational framework. The Working Group also decided in the end that tools and methodology should not be the focal point for a study section. Throughout these discussions considerable attention was paid to the issue of the health of Geriatrics and Rehabilitation Medicine (GRM) and Respiratory and Applied Physiology (RAP) study sections where many muscle applications are currently reviewed.

In the end it was decided to recommend formation of a skeletal muscle biology study section and to examine what would happen to the portfolios of GRM, RAP, and the Cell Development and Function -5 (CDF-5) study sections. The process was to decide whether the applications presented to the Working Group for consideration were, in fact, primarily focused on skeletal muscle biology and should be in the new focus group or whether they should be considered elsewhere. The abstracts reviewed were from applications submitted for the May 2000 Council round.

• Of the 79 abstracts reviewed, 53 applications were judged to be focused on skeletal muscle and could be reviewed in a new skeletal muscle biology group.
• The remaining 26 applications were considered to be more appropriately reviewed in one of the following study sections:

1. Geriatrics and Rehabilitation Medicine (GRM) (16)
2. Respiratory and Applied Physiology (RAP) (4)
3. Cell Development and Function -5 (CDF5) (3)
4. Medical Biochemistry (MED B) (2)
5. Metabolism (MET) (1)

The group of 53 skeletal muscle biology applications was further subdivided into those focused primarily on cellular and molecular biology, or those with an integrative and functional focus. A third set was considered to have components of both groups. Thirty applications were determined to be cellular and molecular and another 17 were integrative and functional, while the remaining 6 were considered to be both.

The Working Group felt that the total number in each of these sub-categories did not constitute a sufficient critical mass to support separate review groups and that there would be problems for the reviewers in calibrating their scores from one round to the next. After further deliberations, the Working Group decided to propose a single skeletal muscle biology review group with the caveat that if there was significant growth the study section could be sub-divided.

The Working Group also felt that the impact on GRM and CDF-5 study sections would be minimal while the consequences for RAP would be more significant. However, the Working Group noted that the 50 plus applications remaining in RAP would be focused on a unified subject area, respiratory physiology.

Because this proposed new review group would consider a broad range of science, the Working Group felt strongly that care must be given to selection of a Chair and SRA who would ensure that this study section would function as a cohesive, integrated group. The Working Group recommended that the name of the new review group be "Skeletal Muscle Biology" or SMB.

Proposed Referral Guidelines for a 
Skeletal Muscle Biology Study Section

This group will consider molecular, cellular, and integrative studies of normal and altered skeletal muscle that range from molecular genetics, to structure-function relationships, to integrative and functional studies on human mobility and health. Integrative projects include studies using multidisciplinary methods and models and studies that transcend organizational levels and systems. Integrative studies may also include development and aging as well as gender and ethnicity difference in muscle function. The goal is to provide a comprehensive review of skeletal muscle biology and muscle diseases, including dystrophies.

•  Molecular characterization of skeletal muscle proteins, including but not limited to actin, myosin, and titin; and supramolecular structures;
• Characterization of skeletal muscle receptors and anchor proteins, including but not limited to dystrophin and the membrane cytoskeleton;
• Cell-cell and cell-matrix interactions, including the basement membrane;
• Generation of force at the molecular and higher levels of organization, and transmission to tendon and bone, including molecular generation of force, mechanical properties of single muscle fibers;
• Supra-molecular assembly and degradation, and regulation thereof;
• Signal transduction pathways in normal and altered states, including but not limited to calcium regulation and acetylcholine receptor structure/function;
• Excitability, EC coupling, and ion channels in skeletal muscle (myotonia, periodic paralysis, malignant hyperthermia);
• Signals and communications in muscle cells and tissues;
• Growth factors, and their receptors;
• Growth, injury, regeneration and repair;
• Molecular and cellular definition of muscle degeneration and regeneration cascades;
• Muscle metabolism and metabolic interactions with other systems;
• Development of skeletal muscle genetic models;
• Mapping, cloning, and mutation/SNP analysis of normal and altered genes;
• Physiological evaluation of skeletal muscle gene function;
• Molecular pathophysiology of skeletal muscle disorders;
• Muscle disease and cell and gene therapy;
• Stem cell biology;
• Pharmacological interventions and pre-clinical approaches to muscle diseases with a special emphasis on the muscular dystrophies, muscle atrophy and inflammatory myopathies;
• Genetic, molecular, biochemical and physiological basis of skeletal muscle adaptation: particularly atrophy, exercise, and inactivity, including maturation and the aging process;
• Muscle cell and organ properties that influence the output of the nervous system;
• Normal and abnormal neural control of muscle fiber type and molecular phenotype;
• Inflammatory processes of muscle at its various levels of organization;
• Mechanisms involved in alterations of skeletal muscle function and capacity due to systemic diseases or to their treatments, such as Type II diabetes and congestive heart failure;
• Physiological interactions between muscle and other systems when skeletal muscle function is the primary focus; and
• Imaging of muscle properties, metabolism, and mechanical dynamics - for example PET, MRS, MRI, and ultrasound.

General Areas of Shared Interest/Overlap Include:

• Studies designed to address general principles of protein or membrane structure, or cell function, and that use skeletal muscle elements primarily as a convenient source of material, should be considered under the auspices of study sections such as: Biological Chemistry and Macromolecular Biophysics, Molecular Approaches to Cell Function, and Interactions; or Fundamental Bioengineering and Technology Development.
• Systemic diseases and treatments that influence muscle function secondarily are not appropriate for review by SMB; when the primary focus is on muscle function SMB may be an appropriate study section.
• The use of skeletal muscle as a platform for gene delivery for non-muscle diseases, such as for hemophilia, or for vaccine development, may be best reviewed elsewhere.
• Application of gene delivery technologies when it is specific for muscle and muscle diseases may be appropriate for SMB, however, development of novel technologies should be reviewed elsewhere.
• Studies designed to address the use of imaging methods primarily to gather information for the diagnosis and differentiation of muscle, tendon and soft tissue diseases belong to the Surgery, Radiology and Bioengineering IRG study sections on Diagnostic Imaging and Diagnostic Radiology. When imaging methods and science are used to elucidate muscle function, to distinguish mechanisms or to test structure-function hypotheses, they are appropriate for review by SMB.
  
  

Areas of Shared Interest/Overlap

Musculoskeletal and Dental Sciences IRG (Specifically, Geriatrics and Rehabilitation Medicine (GRM) and Orthopedics (ORTH) Study Sections)

• Muscle biology and sarcopenia in studies of aging and disability:

1. Studies on muscle-specific mechanisms affecting muscle, function, growth, or atrophy should be reviewed by SMB.
2. Studies on muscle involving interactions with age-related changes in other physiological systems should be reviewed by GRM. This includes both studies of effects of age-related muscle changes on other systems and effects of age-related changes in other systems on muscle.
3. Studies on muscle that are testing hypotheses about mechanisms of aging that affect multiple systems or non-muscle tissues should be reviewed by GRM (e.g., hypotheses on mechanisms of extension of lifespan by caloric restriction).
4. Studies on age-related changes in muscle mass or properties that are part of studies of multiple age-related changes in physiology or body composition (e.g. fat, cardiovascular and bone) should be reviewed by GRM.

• Effects of exercise in relation to aging and disability:

1. Effects on muscle-specific functioning (e.g. contractility, signal transduction mechanisms) should be reviewed by SMB.
2. Effects of exercise on broader age- or disability-related outcomes, physical performance abilities, or other physiological systems should be reviewed by GRM.

• Motor control including studies of normal, disabled, and elderly individuals is best reviewed in GRM or a neuroscience-oriented study section;
• Biomechanics related to muscle activation and control may be reviewed by either SMB or GRM;
• Biomechanical studies involving kinematics of movement and neural control of movement or function should be reviewed by GRM. Biomechanical studies related to gait could also be reviewed by ORTH;
• Study of prostheses, analysis of joint mechanics, and gait studies are not appropriate for review by SMB; these are reviewed by GRM and ORTH; and
• Imaging studies related to muscle (such as metabolic imaging) that are of general interest should be reviewed by SMB. Applications with specific relevance to rehabilitation and aging should be reviewed by GRM. (See also shared interest with MET).

Nutrition and Metabolic Sciences IRG

The following areas of science are most appropriately reviewed in the NMS IRG, except where noted:

• Acute and chronic effects of exercise or hormonal intervention on glucose and lipid metabolism and insulin sensitivity in health and disease;
• Metabolic imaging or spectroscopy of muscle related to glucose or lipid metabolism;
• Dietary changes that effect metabolic function, obesity, insulin; and
• Applications that focus on the effect of nutrition on muscle mass should be reviewed by SMB.
  

Pathophysiological Sciences IRG (specifically, Respiratory and Applied Physiology (RAP Study Section)     

The following areas of science are most appropriately reviewed in the PPS IRG (particularly RAP Study Section), except where noted:

• Applications dealing with the effects of exercise on skeletal muscle should be referred to SMB. Applications dealing with the effects of exercise on the cardiovascular system (e.g., exercise and the control of blood pressure, thermoregulation, etc.) or the respiratory system (e.g., exercise and control of respiration) should be referred to RAP;
• Airway smooth muscle applications should be referred to RAP if they deal with muscle cell contractility per se, or to the Lung Biology and Pathology (LBPA) study section if they deal with asthma/airway reactivity;
• By definition, the SMB study section has excluded cardiac muscle. However, the exercise physiology application involving cardiac muscle remaining in RAP will lack a critical mass. Consideration should be given to grouping the cardiac muscle exercise applications with the exercise applications being moved to SMB. Alternatively, they should be considered in the Cardiovascular Sciences A (CVA) study section; and
• Traditionally, respiratory muscle applications (diaphragm and intercostals muscles) have been reviewed in RAP. These have been few in number and, by chance, none were included in the applications reviewed for the May 2000 Council round. Again, there would not be a critical mass in RAP. It is recommended that applications dealing with the ventilatory action of respiratory muscles should be referred to RAP. Research projects that involve respiratory muscles but are examining basic aspects of muscle function should be referred to SMB.

Cell Development and Function IRG

The following areas of science are most appropriately reviewed in the CDF IRG (particularly CDF-5 Study Section), except where noted:

• Studies examining early events in development, even if they are relevant to skeletal muscle; and
• Other overlapping interests may include regulation of the cell cycle, apoptosis, and skeletal muscle cell senescence.
  
  

Neuroscience IRGs (MDCN, IFCN, or BDCN)

When the issue is motor control and the primary focus is on neural structure and function, the neuroscience groups are most appropriate to review these applications. When the issue is motor control and the primary focus is on the role of skeletal muscle force production, SMB should review the application.

Cardiovascular Sciences IRG

SMB may be an appropriate review venue for cardiomyopathy in Duchenne Muscular Dystrophy.

GENETICS IRG

The following areas of science are most appropriately reviewed in the Genetics IRG:

• Studies of quantitative genetics, genetic epidemiology and genetic analysis of complex traits; and
• Genetically engineered animals with an emphasis on systems physiology.