Lack of physical activity is central to numerous health problems. Despite this, we have limited understanding of the molecular components which confer the benefit of physical activity and their diverse impacts across tissues with respect to age, sex, genetics, environment and other objective physiologic, morphometric, and metabolic measures. Identifying these molecular signatures offers to provide new opportunities for treatment and therapeutics. The goal of the Molecular Transducers of Physical Activity in Humans Consortium (MoTrPAC) is to assemble a comprehensive map of the molecular changes that occur in response to physical activity and, when possible, relate these changes to the benefits of physical activity. This map will be greatly facilitated by the application of ?omics technologies to identify exercise-responsive genes and to relate their benefits across multiple tissues and contexts. We propose to aid in the construction of this map as the Stanford/Salk MoTrPAC Genome, Epigenome and Transcriptome (GET) Chemical Analysis Center. We will leverage our production and analysis experience to engage in MoTrPAC study design, enable the production of high quality and low cost genomes, epigenomes and transcriptomes and facilitate and engage in bioinformatics analysis with the MoTrPAC Bioinformatics Center. Key activities will include coordination and collaboration with all the MoTrPAC sites from tissue management to data delivery. Through these activities we will sequence 3000 genomes and at least 40000 epigenomes and 40000 transcriptomes for samples collected at MoTrPAC animal and human study sites. Our site will engage in multiple levels of quality control from tissue collection to sequence mapping. Generated data in common data formats will be immediately available to MoTrPAC investigators and the Bioinformatics Center through the Google Cloud. In addition, as part of our proposed site, and in coordination with both the MoTrPAC Steering Committee and investigators, we will leverage our expertise in both studies of exosomes and chromatin accessibility sequencing with ATAC-seq to conduct two early pilots that aim to elucidate the systemic and molecular changes in response to physical activity. Additional features of our proposed site are analytical opportunities that include leveraging multiple exercise-related ?omics data sets, such as the DGN study where we have genetic data, transcriptomes and exercise activity recorded for 922 people and have already identified multiple differentially expressed genes and gene-by-environment variants in response to exercise, and diverse and novel -omics methods for gene-by-environment, multi-omics and longitudinal data analysis. Our expectation is that this combination of production experience, exercise-relevant data and novel methods will support diverse and impact research outcomes in the MoTrPAC.

Public Health Relevance

Identification of molecular transducers of physical activity will provide new options to improve the benefit of physical activity and preserve health. A focus of the Molecular Transducers of Physical Activity Consortium (MoTrPAC) is to comprehensively identify these molecular changes with rapid delivery of high quality, low-cost genomics, epigenomics and transcriptomics data. We have proposed to establish a collaborative MoTrPAC Genome, Epigenome and Transcriptome (GET) site which will combine high-throughput technologies with state-of-the-art algorithms and datasets to enable new breakthroughs in identifying the molecular characteristics of exercise and its benefits on human health.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Resource-Related Research Projects--Cooperative Agreements (U24)
Project #
5U24DK112348-03
Application #
9660563
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Maruvada, Padma
Project Start
2016-12-13
Project End
2022-11-30
Budget Start
2018-12-01
Budget End
2019-11-30
Support Year
3
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Stanford University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94304
Luo, Chongyuan; Hajkova, Petra; Ecker, Joseph R (2018) Dynamic DNA methylation: In the right place at the right time. Science 361:1336-1340