Carnegie Mellon University

Monday, July 19, 2010

Josef Franke

Josef Franke Awarded AHA Fellowship

Josef Franke, a postdoctoral fellow in the Department of Biological Sciences recently received the Spring 2010 Fellowship Research Award from the American Heart Association (AHA). For the next two years, the prestigious award will support Franke, a member of Associate Professor Peter Berget’s laboratory, as he develops a novel biosensor assay to dissect the molecular mechanisms by which mutations in the rod domains of myosin II heavy chain proteins lead to cardiac disease.

“Josef is an extremely accomplished researcher and it has been wonderful to have him in the lab,” said Berget who received the Julius Ashkin Award for Excellence in Teaching last year. “This fellowship gives him an opportunity to train in an area of research that will not only position him to be an effective researcher but also a good teacher. ”

Franke received his Ph.D. in Cell Biology at Duke University in 2005, where he first became interested in studying the myosin II family of contractile proteins. These proteins function as molecular machines that bind actin filaments and hydrolyze ATP to generate the force required for constriction of the actin cytoskeleton; depending on the context, the myosin-based constriction leads to cell-shape changes or to the contraction of muscle fibers in muscle cells. Franke’s doctoral work was focused on understanding the role of a myosin II protein in facilitating cell-shape changes critical for embryonic development in Drosophila melanogaster, commonly known as fruit flies. In addition to characterizing these proteins in Drosophila, Franke also studied their human versions, particularly how the structure of these proteins affects their ability to assemble. Following the completion of his graduate work, he joined Rockefeller University as a postdoctoral fellow in 2006 where he further pursued his work on the relationship between protein structure and function. While at Rockefeller, Franke investigated the secondary structure of different protein components of the nuclear pore complex in yeast. Here at CMU, Franke will combine his knowledge of protein structure and the innovative biosensor technology to further assess the disease-causing structural abnormalities in myosin II proteins.

Dominant point mutations in the rod domains of three different myosin II heavy chain proteins, two cardiac muscle heavy chains MYH6 and MYH7 and a smooth muscle heavy chain MYH11, lead to a variety of coronary diseases; however, the molecular mechanisms underlying the pathology of these mutations are largely unknown. The myosin rod domains are required for the assembly of these proteins into higher order secondary structures to form bipolar filaments, which mediate myosin-based contractility. Franke is interested in investigating how mutations in these regions affect dimer structure and assembly characteristics that lead to disease. “As most affected individuals have one wild type and one mutant locus it is predicted that the predominant dimer species will be mutant/wild type heterodimers, in addition to wild-type and mutant homodimers. Interestingly, the presence of heterodimers has not been determined experimentally. Therefore, it is unknown if heterodimers display structural or functional defects which contribute to the pathogenicity of these diseases. I plan to answer these unresolved questions,” said Franke.

To address these questions, he is working to construct a novel, in vivo fluorescence-based biosensor assay using the Fluorescence Activating protein (FAP) and single chain antibody molecule (ScFv) technology developed by Berget in collaboration with the Molecular Biosensor and Imaging Center (MBIC) and the National Technology Center for Networks and Pathways (TCNP). “ This could be a great system to look at and determine if and how these dominant mutant heterodimers are formed. In addition, it can serve as an excellent platform to eventually analyze myosin protein-protein interactions,” Franke explained.

Franke is also a part of FIRST VI, a nation-wide program funded by the National Science Foundation (NSF) that is directed towards enriching the teaching abilities of postdoctoral fellows and future faculty in the sciences. As an active participant, he has attended numerous summer workshops and teaching seminars over the last two years.

Megha Kapur