This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Familial hypertrophic cardiomyopathy (FHC) caused by mutation in the gene encoding cardiac myosin binding protein-C (cMyBP-C) is estimated to affect one in 1,500 Americans. This genetic disorder of the heart is characterized by increased growth in thickness of the left ventricular wall. Despite over 30 years of research, the exact structural location and function of cMyBP-C in muscle cells is far from clear. Our research investigates the structural changes in hearts from genetically-engineered mice which lack cMyBP-C or have cMyBP-C that has been altered to mimic this protein's conformation as it changes in health and disease. We believe cMyBP-C acts to 'put the breaks' on the speed of the contracting cycle in heart muscle cells. Using the approach of X-ray diffraction (on the BioCAT beamline, Argonne National Laboratory), we will probe for changes in the molecular structure of heart muscle cells that arise from removing or altering cMyBP-C in our genetically-engineered mice. In support of our hypothesis, we have already found profound effects on the molecular structure in mice lacking this protein. Additionally, altering the conformation of cMyBP-C affects cardiac function, which may be due to changes in its molecular 'charge'. We will therefore examine structural changes arising from changing the charge on cMyBP-C. Despite advances in biomedicine, the 5-year mortality of heart failure patients remains well above 50%. Thus, understanding the role of cMyBP-C in governing contraction of the heart can lead to development of new treatments such as gene therapy and drugs that control the conformation of cMyBP-C.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR008630-13
Application #
7722750
Study Section
Special Emphasis Panel (ZRG1-BCMB-E (40))
Project Start
2008-04-01
Project End
2008-12-31
Budget Start
2008-04-01
Budget End
2008-12-31
Support Year
13
Fiscal Year
2008
Total Cost
$50,585
Indirect Cost
Name
Illinois Institute of Technology
Department
Other Basic Sciences
Type
Schools of Arts and Sciences
DUNS #
042084434
City
Chicago
State
IL
Country
United States
Zip Code
60616
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