Day 2 :
Keynote: Tissue specific secretomes – A treasure chest for the identification of disease related marker proteins
Time : 09:30-10:30
Stefan Lehr is a Biologist. He is recognized in the field of Clinical Proteome Research particular for his work on tissue specific secretomes and interorgan communication in the context of metabolic disorders. He has published more than 70 papers in ISI journals with more than 1100 SCI citations and an H-factor of 20.
Modulations of tissue-specific secretome profiles, triggered by obesity and sedentary lifestyle or influenced by physical activity are supposed to play a crucial role in the development, prevention and therapy of metabolic diseases including type 2 diabetes. The Deutsches Diabetes-Zentrum (DDZ) established an analysis platform to profile tissue specific secretomes and provide secretome profiles for adipose tissue, skeletal muscle and islets. These comprehensive protein maps, available under diabesityprot.org, will help to achieve a deeper understanding for the complex and dynamic interplay of proteins involved in the communication between different tissues and its alteration in disease pathophysiology. The most crucial step to get closer to this goal is utilizing an adequate sample processing. Preparation according to standard operation procedures combined with close quality control is irreplaceable in order to achieve high quality samples suitable for secretome analysis. Next to this, integration of different proteomic profiling techniques (Gel-based and gel-free MS approaches, Multiplex Immunoassays) is necessary to allow a comprehensive characterization of the complex tissue secretomes. Ultimately, this provides a treasure chest of novel tissue-specific secretion products, which potentially can be used for diagnostic or therapy purpose of metabolic disorders.
Tai Long Pan has been committed to Chinese Medicine Therapy upon hepatic diseases as well as toxicology of environmental factors with functional proteome platform for many years. He has also established a feasible model to systematically and effectively identify the panel markers associated with clinical diagnosis and prognosis. In this study, functional proteome analysis of plasma may provide a promising tool for developing therapeutic strategies and can serve as the basis for further research.
Chromium is an emergent class of toxic metal, which is widely used in numerous industrial processes, and it is difficult to avoid contact or absorption through the skin. In natural environments, chromium generally occurs in two forms: trivalent (Cr3+) and hexavalent (Cr6+) states. Piles of studies have indicated that heavy metals such as chromium compounds are closely linked to cytotoxicity and carcinogenicity via the skin. Meanwhile, exposure to chromium usually results in large-scale protein alterations which reflect pathologic states. Thus, merely exploring the genomic data is not sufficient to reveal biological function caused by chromium compounds. In this regard, the impact of chromium on the human health and the underlying pathogenic processes were further revealed with functional proteome tools combined with a network analysis to statistically explore candidate protein targets and related pathways predicted to be changed in the presence of chromium compounds. Our findings showed that the most meaningful changes were observed amongst proteins involved in inflammation, carbohydrate metabolism, endoplasmic reticulum (ER) stress, calcium homeostasis and apoptosis. Pathway analytical tools suggest that Cr6+ might induce the accumulation of misfolded proteins and adverse effects leading to cell apoptosis and liver injury, while Cr3+ was shown to be non-mutagenic and is actually required for normal metabolism. Taken together, we systemically detect the protein profiles as well as to correlate the proteome results with data from other functional studies in the presence of topically applied chromium compounds. The proteins and molecules identified are key components in determining the inflammatory responses, hepatic pathology and carcinogenesis. The current researches provide important information on the protein panel markers and mechanisms associated with chromium cytotoxicity and advanced damage in the public health.
Yoshitaka Bessho is a Structural Biologist recognized in the field of Nucleic Acid and Protein Research, with a particular focus on tRNA and the genetic code. He served as an Assistant Professor at Nagoya University, Japan in 1992. After his service as a Japanese Governmental Overseas Research Fellow at SUNY Buffalo in 1998-99, he moved to RIKEN Yokohaama Institute in 2001 as a Researcher for Protein Structural projects. Since 2009, he has served as the Team Leader of the Functomics Biology group at RIKEN SPring-8 Center, Japan. He is now a Visiting Professor at Academia Sinica, Taiwan, seeking to promote international collaboration projects between Japanese/Taiwanese synchrotrons. His research is focused on developing structure-based system biological science, and he is engaged in the technical development of the synchrotron and the XFEL (X-ray Free Electron Laser). In addition, he is a Founder of the Japanese Society for the study in origin and evolution of primary biomaterials for common cellular activities. His achievements include research in the origin and the evolution of the central dogma of life.
Advances in X-ray technologies have contributed to the development of structural biology and life sciences. In this research, the principles underlying the central dogma of life will be clarified by structure-based analyses of nucleic acids and their related enzymes, involved in tRNA maturation and ribosomal translation, as the key elements for the genetic and protein composition systems. X-ray crystallography is the one of most important core technologies for protein structural analysis. Recent progress in protein microcrystallography now allows us to analyze extremely small crystals that have grown poorly or suffer from rapid radiation damage. In addition, the further technological development of the X-ray Free Electron Laser (XFEL) is expected to enable the observation of the structural fluctuations of proteins in solution or in the transition states of certain reactions. XFEL has the potential to facilitate bio-molecular imaging in solution in very short times, with accuracy on the ten-femto-second order. We have successfully obtained genuine coherent X-ray speckle patterns from living bacterial cells, as well as from purified gigantic bio-molecules, such as ribosomes. High-quality coherent X-ray diffraction patterns were recorded from intact Microbacterium lacticum cells. An image re-constructed from the X-ray diffraction pattern revealed the natural nanoscale structures within live cells, thus providing clues toward understanding nucleoid structures, which are inaccessible by other methods. The technologies of this research will potentially create breakthroughs in whole cell biology, and contribute toward single-molecule imaging in the future with XFEL. Through structural and functional analyses, as well as basic research in bio-imaging, the entire networks of the molecules could be revealed in the future, as the complete cellular system. We will discuss the recent results of our projects in this presentation.