P7: Structural elements of muscle

Subproject Speakers
Berlin: Michael Gotthardt, MD, Prof.
Paris:  Gisèle Bonne, PhD

The giant muscle protein titin functions as elastic scaffold to aid the orderly assembly of the sarcomere and determines the biomechanical properties of muscle. Both features depend on titin's protein domain composition, which is regulated by alternative splicing. Recently, additional functions for titin have been proposed based on its interaction with metabolic enzymes and proteins involved in signal transduction, as well as the titin kinase (TK) domain. The TK domain resides at titin's M-band and shows homology to the serine/threonine kinase domain of smooth muscle myosin-light chain kinase (MLCK) and the invertebrate muscle proteins twitching and stretching-MLCK. In our preliminary studies we used mouse genetics to address titin's role in cardiac signal transduction in vivo and uncovered crosstalk between adrenergic and titin signaling at the level of Ca2+ handling. Here, we will build on the data obtained in our conditional knockout of titin's M-band region that mimics the phenotype of human patients described by Dr. Ferreiro.



Maria Chatzifrangkeskou, MyoGrad doctoral student 2013-2016

Completed doctoral project:
Roles of ERK1/2 signaling in LMNA-cardiomyopathy

Date and place of thesis defense:
November 8, 2016 in Paris
Joint doctoral degree from UPMC, Paris VI and from FU Berlin



Laurianne Davignon, MyoGrad doctoral student 2010-2015

Completed doctoral project:
Identification and characterization of new genes associated to multiminicore disease

Date and place of thesis defense:
January 20, 2015 in Paris
Joint doctoral degree from UPMC, Paris VI and  from FU Berlin



Nada Essawy, MyoGrad doctoral student
Master, Pharmacogenetics and Stratified Medicine
University College London, UK

Working title
Emerin missense mutations in patients with isolated cardiac defects: self-assembly, interactions and phosporylation


Martina Fischer, MyoGrad doctoral student 2013-2017


Completed doctoral project:
Mechanosensing defects and YAP-signaling in LMNA-related dystrophy

Date and place of thesis defense:
June 28, 2017 in Berlin
Joint doctoral degree from UPMC, Paris VI and from FU Berlin



Coline Macquart, MyoGrad doctoral student 2014-2017


Completed doctoral project:

Role of gap junctional protein connexion-43 in the cardiac disease caused by mutations in the gene encoding A-typ lamins

Date and place of thesis defense:
December 14, 2017 in Paris
Joint doctoral degree from UPMC, Paris VI and from FU Berlin



Christopher Polack, MyoGrad doctoral student 2010-2015

 

Completed thesis project:

Function of titin in striated muscles in health and disease

Date and place of thesis defense:
October 15, 2015 in Berlin
Doctoral degree from FU Berlin



Christine Schwartz, MyoGrad doctoral student 2012-2016


Completed PhD project:

Muscle LIM protein and nesprin-1 in mechanotransduction

Date and place of thesis defense:
September 29, 2016 in Berlin
Joint doctoral degree from UPMC, Paris VI and from FU Berlin



Esma Ziat, MyoGrad doctoral student 2011-2015

Completed doctoral project:

Emery-Dreifuss muscular dystrophy-associated FHL1 gene mutations: study of molecular and functional consequences in skeletal muscle

Date and place of thesis defense:
September 29, 2015 in Paris
Doctoral degree from UPMC Paris VI