Grant: Foundation Grant

University of Calgary

$2,420,842.00

Cellular and Molecular Biomechanics of the Musculoskeletal System

FY 2014-15

Summary

Overarching Direction and Major Questions: I am a musculoskeletal biomechanist and a Canada Research Chair in Cellular and Molecular Biomechanics. My group’s research has been focussed on two areas of continued CIHR support: (i) exploring the molecular mechanisms of striated muscle contraction, and (ii) determining the molecular and cellular mechanisms causing osteoarthritis (OA). In the field of muscle contraction, we demonstrated that major properties of muscle cannot be explained with the primary paradigm of muscle contraction: the cross-bridge theory. Using pioneering approaches, we established that the structural protein titin is involved in force regulation in striated muscles. However, the molecular details of titin’s role remain unknown. Our overarching research question will be to identify the role of titin in force regulation in healthy and diseased skeletal and cardiac muscles. In the area of OA onset and progression, we developed novel technologies for live cell imaging and used these approaches in conjunction with pre-clinical models of post-traumatic and metabolic OA. We also developed techniques for detecting structural and metabolic changes in experimental joints within days of intervention. Our overarching focus in this area will now be on (i) identifying interventions that will slow, or stop, the progression of OA, and (ii) translating the pre-clinical model results to viable interventions in clinical environments. Effects of Anticipated Results: In striated muscle contraction, we will change the fundamental understanding of how muscles produce force and will be able to explain many previously unexplained properties of muscle. Mutations of the titin gene cause more than 40 forms of dilated cardiac myopathies and a dozen skeletal muscle dystrophies. A basic understanding of titin’s functional role might lead to effective treatment interventions for these diseases. In the area of OA research, we will test pharmaceutical, exercise, and nutritional interventions in our post-traumatic and metabolic pre-clinical models of OA. Our results will inform research on human patients, and we will attempt to translate these findings into clinical studies and the health care system through the Alberta OA Team which I am directing. Core Expertise: In the area of muscle contraction, we were the first to perform mechanical and physiological testing on single sarcomeres. We are also leading technological advances in single myofibril testing, and remain the only group that has the equipment and expertise to perform mechanical testing of muscle tissue on all structural levels: from protein-protein interactions to whole muscles. In the area of OA, we pioneered technologies of in vivo cell mechanics and signaling, and the early detection of structural changes in cartilage following experimental interventions. We also established a first reversible, pre-clinical model of muscle weakness, and developed a reliable model of diet-induced obesity resulting in metabolic OA. Mentoring: I am currently mentoring/supervising a team of 8 research associates and 21 trainees. My trainees are exposed to state of the art molecular and cellular biomechanics approaches using micro-, nano- and pico- technologies in an environment of expert support. We have weekly group and individual meetings, and trainees are embedded in an environment of cutting edge equipment and facilities, outstanding research personnel support, and a track record of scientific excellence.

Department

Canadian Institutes of Health Research

Program

Foundation Grant

Recipient

University of Calgary

Location

Alberta, Canada

Recipient Type

Academia

Type

Grant

Source

CIHR Funding Decisions Database

As published

312403

Name

Herzog Walter

Region

Alberta

Country

Canada

Orgtype

Institution Paid; Research Institution

Instname2

Musculoskeletal Health and Arthritis

Theme2

Biomedical

Prcname2

Foundation Grant

Projecttitle

Cellular and Molecular Biomechanics of the Musculoskeletal System

Programtype2

Operating Grants

Orgnameinp2

University of Calgary

Cihramount2

$2,420,842

Cihrequipment2

Programname2

Foundation Grant

Keyworddelim

Cardiac Muscle; Cartilage; Cellular Biomechanics; Cerebral Palsy; Mechanisms Of Contraction; Molecular Biomechanics; Muscular Dystrophies; Osteoarthritis; Pre-Clinical Models Of Msk Disease And Injury; Skeletal Muscle

Competitiondate

201409

Approvedterm2

7 yrs 0 mth

Pinamesdelim

Herzog, Walter

Approvedterm

7 ans 0 mois

Cihrcontribution2

~ $2,420,842~ $0~

Abstract

<html> <body> Overarching Direction and Major Questions: I am a musculoskeletal biomechanist and a Canada Research Chair in Cellular and Molecular Biomechanics. My group’s research has been focussed on two areas of continued CIHR support: (i) exploring the molecular mechanisms of striated muscle contraction, and (ii) determining the molecular and cellular mechanisms causing osteoarthritis (OA). In the field of muscle contraction, we demonstrated that major properties of muscle cannot be explained with the primary paradigm of muscle contraction: the cross-bridge theory. Using pioneering approaches, we established that the structural protein titin is involved in force regulation in striated muscles. However, the molecular details of titin’s role remain unknown. Our overarching research question will be to identify the role of titin in force regulation in healthy and diseased skeletal and cardiac muscles. In the area of OA onset and progression, we developed novel technologies for live cell imaging and used these approaches in conjunction with pre-clinical models of post-traumatic and metabolic OA. We also developed techniques for detecting structural and metabolic changes in experimental joints within days of intervention. Our overarching focus in this area will now be on (i) identifying interventions that will slow, or stop, the progression of OA, and (ii) translating the pre-clinical model results to viable interventions in clinical environments. Effects of Anticipated Results: In striated muscle contraction, we will change the fundamental understanding of how muscles produce force and will be able to explain many previously unexplained properties of muscle. Mutations of the titin gene cause more than 40 forms of dilated cardiac myopathies and a dozen skeletal muscle dystrophies. A basic understanding of titin’s functional role might lead to effective treatment interventions for these diseases. In the area of OA research, we will test pharmaceutical, exercise, and nutritional interventions in our post-traumatic and metabolic pre-clinical models of OA. Our results will inform research on human patients, and we will attempt to translate these findings into clinical studies and the health care system through the Alberta OA Team which I am directing. Core Expertise: In the area of muscle contraction, we were the first to perform mechanical and physiological testing on single sarcomeres. We are also leading technological advances in single myofibril testing, and remain the only group that has the equipment and expertise to perform mechanical testing of muscle tissue on all structural levels: from protein-protein interactions to whole muscles. In the area of OA, we pioneered technologies of in vivo cell mechanics and signaling, and the early detection of structural changes in cartilage following experimental interventions. We also established a first reversible, pre-clinical model of muscle weakness, and developed a reliable model of diet-induced obesity resulting in metabolic OA. Mentoring: I am currently mentoring/supervising a team of 8 research associates and 21 trainees. My trainees are exposed to state of the art molecular and cellular biomechanics approaches using micro-, nano- and pico- technologies in an environment of expert support. We have weekly group and individual meetings, and trainees are embedded in an environment of cutting edge equipment and facilities, outstanding research personnel support, and a track record of scientific excellence. </body> </html>

View source data CIHR Funding Decisions Database (Canadian Institutes of Health Research)