Speaker

 Prof.Peter Csermely,Semmelweis University, Department of Medical Chemistry, P.O.Box 260, H-1444 Budapest 8, Hungary

　　Title

   Determination of overlapping network communities and their implications from marketing to drug design   

　　Time

　　Venue

　　Hall

　　Abstract

Our multidisciplinary group (www.linkgroup.hu) uses the general properties of networks as ‘highways’ making the transfer of concepts between various disciplines rather easy. This allows the utilization of the ‘wisdom’ of biological systems surviving crisis events for many billions of years. As an example of ‘crisis’ in biological systems the community structure of the protein-protein interaction network of stressed yeast cells was studied using our Moduland program, which is a novel method family to detect pervasively overlapping communities (PLoS ONE 7, e12528, www.linkgroup.hu/modules.php). Upon heat shock the compactness of yeast protein communities increased and the number of community-bridging nodes decreased (PLoS Comput. Biol. 7, e1002187). The stress-induced decrease of inter-modular connections was beneficial, since it A.) allowed a better focusing on vital functions, and thus spared resources; B.) localized damage to the affected communities; C.) reduced the propagation of noise; D.) allowed a larger ‘degree of freedom’ of the individual communities to explore different adaptation strategies; and E.) allowed a more adaptive re-organization of the network from pre-formed elements during/upon relief from stress. From this and other studies community reorganization emerges as general and novel systems level mechanism of cost-efficient adaptation, evolvability, learning and memory formation.

Our studies showed that community-bridging nodes play a particularly important role in adaptive processes. In yeast stress inter-community contacts were maintained and developed by key proteins of cell survival. Our signaling database, SignaLink (www.SignaLink.org) revealed that cross-talks between signaling pathways are much more characteristic to humans than to C. elegans or Drosophila. Community-bridging nodes have a key role in protein structure, metabolic and social networks. We proposed to call highly dynamic community-bridging nodes as creative nodes in 2008. These nodes can be identified by their efficiency in perturbation-propagation using our recently developed Turbine program (www.linkgroup.hu/Turbine.php) or by their game centrality, i.e. the ability of a node or edge to establish or break cooperation in a repeated social dilemma game using our program NetworGame (www.linkgroup.hu/NetworGame.php).

Network-based drug targets are often hubs, i.e. central nodes of the networks. However, most diseases affect differentiated cells, which have rigid networks. If rigid networks are attacked at their most central nodes, they easily become over-saturated, over-excited. This may lead to increased side-effects and toxicity. Therefore, rigid networks need to be attacked at their most plastic segments, which are in the neighborhood of the most central network nodes. Importantly, this is the drug targeting strategy of differentiated cells in all other diseases (Pharmacology & Therapeutics, 138, 333-408). Plastic segments often connect rigid clusters and involve inter-community, creative nodes.

In conclusion, community-bridging nodes emerge as novel regulators of adaptation, evolvability, as well as important targets from marketing strategies to drug design.

　　Affiliation

   生于1958年10月7日。Peter Csermely教授在生物化学、系统生物学和复杂网络等研究领域都有突出的成就。他在1985年首次发现了锌在淋巴细胞活化中的重要作用，多年后神经和免疫细胞中的锌信号通路才被人们普遍接受。他还发现了Hsp90的一个低亲和力ATP结合。他提出并初步证实了一个理论，即衰老引起的分子伴侣超负荷，导致了蛋白质的错误折叠，是产生许多文明病的重要原因。在生物医药公司担任首席科学家的经历使得Csermely教授认识到在网络水平上研究多靶点药物会更加有效。于是从2003年开始，他将越来越多的时间和精力都投入到复杂网络及其在生物学与生物化学中的应用研究中。他和他的研究团队开发了多个网络分析软件。他将这些工具用于大量的实际网络中，发现了网络模块之间的重叠和桥梁对于网络在危机事件中的适应机制具有重要作用。