Objective
Research objectives and content
Titin is a giant protein of vertebrate striated muscles. Titin has a molecular weight of 3,000 kDa, and is the largest known protein. Single titin molecules are more than I mum long, and form a filament system which links the Z-discs to the M-lines. Little is known about the interactions that integrate the titin filament into the sarcomere. My first objective is to perform a covering search for ligands of the titin filament by the yeast two-hybrid approach. Identified clones that possibly interact with the titin will be sequenced and expressed in E. coli. Proteinbiochemical studies will test which clones are indeed titin-binding proteins, and will allow a fine-mapping of the interacting domains. The titin filament also contains domains of presumably regulatory functions such as calpain protease binding domains, and a kinase domain. Possibly, novel insight into the muscle physiology and pathophysiology of striated muscle will be obtained by the study of factors which interact with titin's regulatory elements. My second objective will be to test the functions of the novel titin ligands. I will express the identified titin ligands transiently in myocytes, and characterize in detail the functional consequences of this on the myogenesis, and on sarcomeric assembly.
Training content (objective, benefit and expected impact)
The team I will join is internationally leading in titin research and is well-integrated into a network of international collaborations. My PhD project will introduce me to techniques for expressing protein domains in a variety of heterologous overexpression systems (yeast, E. coli, mammalian cells). I will purify identified domains to homogeneity, and thereby obtain a thorough training in proteinbiochemical methods. The study of the interaction of titin and titin ligand domains will use modern methods of evaluating protein/protein interactions in vivo and in vitro. I expect to publish relevant findings in internationally well known and peer-reviewed journals, and to obtain my PhD from EMBL.
Links with industry / industrial relevance (22)
My master thesis project was carried out in the company, Novo Nordisk A/S, which is internationally engaged in molecular diagnostics. Therefore, I have already obtained some insight into how biotechnology applications are relevant to industry. My PhD project will give me a thorough training in modern molecular biology, which at a later stage may make me able to establish myself in the general field of biotechnology and molecular medicine, possibly in a sector which links basic and applied research.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences basic medicine physiology pathophysiology
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences biological sciences molecular biology
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
69012 Heidelberg
Germany
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