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2012”N2ŒŽ2“ϊi–؁j16:00-18:00

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Attila Glatz@”ŽŽm

 

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Membrane-associated gardedams: from cyanobacteria to fission yeast

 

 

Molecular chaperones are known to interact with damaged proteins preventing their aggregation and promoting their folding. Using Synechocystis PCC6803 as a model, we were able to show that the chaperone genes (especially hsp17) is induced under isothermal conditions when cells were treated with membrane perturbing agents. This led to the gmembrane as sensorh idea supposing that not only unfolded proteins, but changes in membranefs physical state might induce the overexpression of chaperones. Moreover, Hsp17 is able to bind and protect membranes upon heat stress. Other chaperones (eg. GroESL) can also associate to membranes while retaining their intact gfoldaseh activity. Recently, we have started to study the chaperone systems of a gmicromammal modelh Shizosaccharomyces pombe. We could demonstrate that the two alpha-crystallin type-HSPs of the fission yeast are differently induced upon heat stress. In addition, both recombinant sHSPs tested are able to bind to model membranes made of S. pombe lipids and preferentially to lipid membranes derived from low temperature adapted cells, indicating that sHSP-membrane interactions might have stress protecting role in higher Eukaryotes as well.

 

 

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Imre Gombos@”ŽŽm

 

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Membrane as a heat sensor: Membrane imaging from heterogeneous cell populations to single molecules

 

 

The heat shock response (HSR) is one of the most ancient and evolutionarily conserved protective mechanisms found in nature. The study of the cellular stress response is of great importance to our understanding of how cells respond and adapt to various changes in their environments especially during different pathophysiological conditions. We demonstrated that not only heat induced protein denaturation can initiate HSR but cellular membranes are also act as sensitive thermal sensors even for mild heat stress. The present knowledge of gene expression and cellular responses is known to derive from analyses of heterogeneous populations. Although this approach provides useful insights into average population responses, they do not furnish information on individual cells or subpopulations. In my presentation: 1.) I will characterize the individual variability in the stress response of genetically homogeneous cell population with ultrasensitive high content imaging. More specifically, to link the population heterogeneity of the heat shock response and membrane structure (raft organization and dynamics) in mammalian cell cultures. The identification of specific changes in membrane domain structure leading to selective refinement of heat shock proteins in a heterogeneous cell population could help us to understand why a small subpopulation of cells could determine the outcome of important disease states. 2.) As an exploitation of the above principles next I will introduce the mode of action of a small molecule heat shock protein (HSP) co-inducer. In my presentation I will discuss in vitro molecular dynamic simulation, experiments with lipid monolayers and in vivo ultrasensitive fluorescence microscopy, which showed that BGP-15 alters the organization of cholesterol-rich membrane domains. Imaging of nanoscopic long-lived platforms demonstrates that BGP-15 prevents the transient structural disintegration of rafts induced by fever-type heat stress and able to remodel cholesterol-enriched lipid platforms. BGP-15 inhibits heat shock factor 1 (HSF1) acetylation thereby prolongs the duration of HSF1 binding to heat shock elements. These data indicate that BGP-15 has the potential to become a new class of pharmaceuticals for use in emembrane-lipid therapyf.