Day 1 :
Cleveland Diagnostics, USA
Time : 9:35-10:05
Boris Y Zaslavsky is a Bioanalytical Chemist. He graduated from Moscow State University in 1967, PhD in 1972; DSc in 1985 from USSR Academy of Sciences, Moscow, USSR. From 2012-present, he is a Chief Scientific Officer of Cleveland Diagnostics, Cleveland, OH, from 1997-present, he is a Vice President, Director of Research and Cofounder of Analiza, Inc., Cleveland, OH. He has over 180 publications in peer-reviewed journals, 1 monograph, over 10 USA and international patents issued. His research interests are: Clinical proteomics, role of water in biology, and aqueous two-phase systems.
Coordination of numerous cellular biochemical reactions in space and time is achieved by compartmentalization. In addition to intracellular membranes acting as physical barriers for several cellular organelles there is a multitude of membrane-less organelles formed by liquid-liquid phase separation. The principles governing phase separation and functions of such organelles in vivo are poorly understood as of now. However, the much better studied aqueous two-phase systems formed by two polymers may serve as a model of membrane-less organelles. Such systems originate from polymer influence on the solvent properties of water. The phase forming polymers may include proteins and polysaccharides. The differences between solvent features of aqueous media in the two phases may be quantified and manipulated by polymers’ concentrations and additives of inorganic salts or small organic compounds, such as sucrose, sorbitol, etc. The differences between electrostatic properties of the phases as well as those between solvent features may be quantified using partitioning of homologous series of charged compounds and solvatochromic dyes as molecular probes for the solvent dipolarity/polarizability, solvent H-bond donor acidity, and solvent H-bond acceptor basicity. The differences between solvent features and electrostatic properties of the phases govern unequal distribution of proteins and other natural compounds in aqueous two phase systems and in membrane-less organelles. This solvent-driven partitioning, and not the “normal” protein-protein interactions, might cause enrichment of some proteins within the membrane-less organelles. It will be shown that proteins may influence solvent features of water and their effects are similar or exceeding those displayed by common macromolecular crowding agents and organic osmolytes. It is suggested that the effects of proteins on the solvent features of aqueous media may regulate the phase separation in vivo.
Kaohsiung Medical University, Taiwan
Time : 10:05-10:35
Bin Huang obtained his PhD degree from the Department of Plant Science, National Taiwan University. He then focused on Cardiology during his Postdoctoral studies. He became experienced in the gaseous molecule-mediated post-translational proteome, particularly in the NO-mediated S-nitrosylation when studying endothelial cells of the vascular system. He became interested in the behavior of mitochondrial fusion/fission when studying cell aging and drug-resistance of cancer cells. In addition to these research interests, he develops the Center for Stem Cell Research of Kaohsiung Medical University as the Vice Director.
Nitric oxide (NO), an endogenous evolutionary gaseous molecule with labile character can bind to cysteine residues (Cys-NO, S-nitrosylation) and then alter the enzyme activity. NO is regarded as a mild reactive oxygen/nitrogen species (ROS/RNS) that can compete with other, more potent ROS/RNS, and protects cells from irreversible oxidative stress caused by free radicals. At present available methodologies applied to study the implications of NO in physiological responses include Western blotting to measure the phosphorylation of endothelial nitric oxide synthase (eNOS) at Ser1177 and Ser633 residues and detecting gaseous NO by Griess reagent. However, this reagent is greatly affected by the presence of peroxinitrite (ONOO−). Therefore, the new fluorescent probe - 5-amino-2-(6-hydroxy-3-oxo-3H-xanthen-9-yl) benzoic acid methylester (FA-OMe) - that specifically binds to endogenous NO, was developed and utilized. As a result, the elevated production of NO can be estimated not only by eNOS phosphorylation in Western blots but also by direct quantification using FA-OMe. Once it became possible to confirm the production of NO, the identification of the subsequent protein S-nitrosylation resulted from NO binding to the cysteine residues became important. The utilizations of commercialized antibody and mass spectrometric devices were reported to detect the Cys-NO residue directly. However, for the reason of poor antibody specificity and weak chemical binding of Cys-NO, both two methods were not reliable. We therefore designed a tag-based labeling system on cysteine residue that modified from biotin-switch, (e.g. IAA, IAM and iTRAQ). Cys-NO will be replaced by these tags and was then detected either by 2-DE-based Western blot or mass spectrometry with identical molecular weight shifts. The whole profiles of enzyme activation, gaseous NO molecule production, and the subsequent protein S-nitrosylation could be analyzed simultaneously to explain more details about the physiological mechanisms of action in protein S-nitrosylation.
Bio-Modeling Systems, France
Keynote: The future of systems medicine: Everything you always wanted to know about the “reality” of big data and AI “big mirages” but were afraid to ask
Time : 10:55-11:25
Manuel Gea is a Serial Entrepreneur, Co-Founder of the world’s first Mechanisms-Based Medicine Company, thinking & doing out of the box applying “general semantics” principles and Augmented Intelligence vs. Artificial Intelligence. He is a Keynote Speaker, independent board member, expert & business angel developing disruptive innovations (technologies, novel therapies & business models) in the life sciences, IT, pharma, healthcare & cosmetic sectors. He is graduated from Ecole Centrale Paris in operational research and data integration, and has Sociology of Organizations degree from Paris IX Dauphine University. He is also Chairman of the Independent trans-discipline biotech Think Tank Adebiotech, and the Co-founder and Chairman of Centrale-Santé, the French Health Think-Tank gathering 2500 members, professional involved in sector innovations and creating value for patients. He is Co-founder, CEO & VP R&D IT of BMSystems, dedicated to the discovery of cost-effective new therapeutic, diagnostic & preventive solutions.
Statement of the Problem: With a 95% failure rate, the Big Pharma R&D model focused on testing new patentable compounds for novel targets based on KOL concepts is not more pertinent for at least 3 reasons: 1) Despite decades of investments in Omics technologies and Systems Biology programs produced few relevant results due to 3 “side effects” and a conceptual mistake: Life mechanisms are complex not complicated! 2) The “mirage” of Artificial Intelligence (AI) that MUST follow rules in a world where humans massively do not. 3) The unreliability of scientific and clinical publications is increasing, and the valuable negative results are not published. Why the transfer of the digital tools and methods does from the internet world to the life sciences R&D world does not work properly. One reason is that the founding basements of the two worlds do not obey the same rules. The challenge is not a question of technologies only, its needs to redefine discovery concepts.
The Future of Systems Medicine: 1) Understanding and validating the mechanisms of a disease/disorder becomes the first objective. 2) Finding the most adapted solutions is a necessary consequence. The Mechanisms-Based Medicine Concept gives the basements to apply CADI™ (Computer Augmented Deductive Intelligence) Discovery that addresses life mechanisms complexity and the unreliability of scientific and clinical publications by combining the strengths of human and artificial intelligences in the right order.
The 5 CADI™ Discovery Principles: 1) Mechanisms-Based Medicine Concept; 2) Architectural Principle; 3) Negative Selection Principle; 4) Steps Validation Principle; 5) Integrated Solutions Principles.
Conclusions: CADI Discovery already led to a world’s first in neurodegenerative diseases, 1 therapeutic spin-off and 1 exclusive our license, 4 issued patents, 10 publications, and 39 CADI™ programs among completed or open for collaboration.
1. F Iris F, D Filiou, Ch W Turck (2014) Differential proteomics analyses reveal anxiety-associated molecular and cellular mechanisms in cingulate cortex synapses. American Journal of Psychiatry and Neuroscience 2(3): 25-42.
2. Iris F (2012) Psychiatric systems medicine: closer at hand than anticipated but not with the expected portrait. Pharmacopsychiatry 45 (Suppl. 1): S12–S2.
3. Turck CW, Iris F (2011) Proteome-based pathway modelling of psychiatric disorders. Pharmacopsychiatry 44 (Suppl 1): S54-61.
4. Iris F, Gea M, Lampe PH and Santamaria P (2009) Production and implementation of predictive biological models. Med Sci. 25: 608-16.
5. Iris F, Gea M, Lampe PH and Santamaria P (2009) Production and implementation of predictive biological models. Med Sci. 25: 608-16.