(FOA)-MoTrPAc
Phase 2 Animal Studies (U01 Clinical Trial Not Allowed); February 20,
2020
Agency
NIH
Description
The
purpose of this FOA is to invite applications for Preclinical Animal Study Sites
(PASS) as part of the Molecular Transducers of Physical Activity in Humans
Consortium (MoTrPAC) (http://commonfund.nih.gov/MolecularTransducers).
Awards made through this FOA will support preclinical mechanistic studies on a
range of molecular compounds identified in the initial PASS exercise protocol
which was designed to complement and substantially expand the data from the
human clinical study in MoTrPAC. This FOA is
expected to support up to 4-6 additional Preclinical Animal Study Sites (PASS)
as part of the MoTrPAC.
The
work of the three existing PASS is divided into two phases. In Phase 1, the
investigators developed and utilized treadmill running and tissue sampling
protocols for Fisher 344 rats that parallel and greatly expand the potential
impact of the MoTrPAC clinical protocols for active
and sedentary volunteers. The PASS Phase 1 included two separate arms to examine
the response of two age groups (6 and 18 months) of male and female animals to
either an acute bout of exercise or to an intensive and progressive aerobic (70%
VO2max) training protocol ranging from one to eight weeks in length. Harvesting
tissues from both acutely- and training-exercised Fisher 344 rats along with
appropriate sedentary controls has been completed, and the tissues have been
distributed to the Chemical Analysis Sites for analysis according to MoTrPAC guidelines
In
Phase 2 the three original PASS study sites are designing and conducting
detailed mechanistic studies to identify the sources, signaling pathways,
physiological targets, and functions of mobilized and identified molecular
transducers of physical activity; recognize feedback and interaction effects
among different pathways and tissues; and discover specific roles of the
molecules associated with specific health benefits. The original three PASS
sites have begun analyses of mechanisms involved in transducing the effects of
exercise. Preliminary data from five abundant PASS tissues indicate that
molecular signals produced by physical activity are abundant and diverse (MoTrPAC-data.org)
In
view of the enormous number of molecules mobilized in the two treadmill exercise
arms of the study, this new RFA calls for additional applications to join the
consortium for the remainder of the MoTrPAC funding
period to explore the mechanistic links between the candidate molecular
transducers of physical activity and functional effects of exercise in tissues.
Building on existing and future animal and human data, such preclinical studies
will extend knowledge of the benefits of molecular transducers of exercise.
Overall, data from existing and newly funded PASS studies are anticipated to
substantially increase our understanding of how tissues and organs other than
muscle, fat and blood adapt to the exercise induced changes. Data from the 19
PASS tissues will extend the analyses of candidate transducers of physical
activity from the clinical study (muscle, adipose tissue and plasma) across
multiple organs and tissues that are not accessible from human participants.
Applicants should propose what they think is the best strategy and approach for
investigating how these mobilized compounds synergize to coordinate the overall
homeostatic response to exercise in a variety of tissues. Grantees from this RFA
will work in conjunction with the MoTrPAC Steering
Committee (of which they will be members) to finalize the molecules that will be
investigated
The
MoTrPAC Bioinformatics Center (BIC) will conduct a
data Webinar for interested applicants at a date to be announced on the MoTrPAC Data Hub Website, the MoTrPAC site, and the Common Fund site soon after
publication of this FOA.
Activity
Code
U01
Announcement
Number
RFA-RM-20-009
Closing
Date
Letter
of Intent (optional) due Feb. 20, 2020. Application due March 20,
2020.
Link
to Full Announcement
https://grants.nih.gov/grants/guide/rfa-files/RFA-RM-20-009.html