Andrea Heinz
Dr. Andrea Heinz
Institute of Pharmacy, Pharmaceutical Technology and Biopharmacy
Wolfgang-Langenbeck-Straße 4
06120 Halle (Saale)
Tel.: +49 (0) 345-55 25220
Email: andrea.heinz@pharmazie.uni-halle.de
Structure, formation and turnover of elastic fibers
The project aims to investigate the structure of the important extracellular matrix protein and core protein of elastic fibers, elastin. The biopolymer elastin exhibits unique properties including elasticity and extreme durability and is, hence, critical for the long-term function of various vertebrate tissues and organs including lung, skin and major blood vessels. The project also deals with the investigation of interactions between elastin and elastic-fiber proteins such as fibrillin, fibulins and microfibril-associated glycoproteins to get insight into the formation and structure of elastic fibers.
Even though it is known that elastin is composed of units of its precursor tropoelastin, which are connected via lysine residues and form a variety of polyfunctional cross-links, almost nothing is known about the exact structure and cross-linking pattern of elastin due to its remarkably high hydrophobicity and resistance that make structural investigations challenging. However, elucidating elastin’s structure would be of great importance to better understand its functions in healthy tissues as well as structural changes that go along with cardiovascular diseases such as atherosclerosis and lung emphysema. Therefore, in the scope of this project, intact elastin fibers will be isolated from human aorta, skin and cartilage using a method optimized for small tissue biopsies. Subsequently, elastin samples will be degraded using specific elastases and an identification of cross-linked peptides by complementary mass spectrometric techniques will allow determining the exact positions of cross-links as well as the domains of tropoelastin molecules involved in cross-linking. Moreover, the interactions of tropoelastin, fibulin-5 and fibrillin-1 will be investigated in detail. Overall, the project will provide a comprehensive and significant insight into the structure of elastin which will aid in the development of directed therapies against diseases of elastic tissues.