Thesis topic proposal
Zsolt Török
Cell-to-cell variation of stress response: role of plasma membrane nanostructure


Institute: University of Szeged
environmental sciences
Dcotoral School of Environmental Sciences

Thesis supervisor: Zsolt Török
Location of studies: Szegedi Tudományegyetem
Abbreviation of location of studies: SZTE

Description of the research topic:

Cellular stress response is of great importance to our understanding of how cells respond and adapt to various changes in their environment especially during pathophysiological conditions. Considerable evidence has been accumulated to the favor of the "Membrane Sensor Hypothesis" which predicts that the level and ratio of stress proteins (HSPs) are changed as a result of alterations to the plasma membrane. The aim of the current project is to identify heat induced specific alterations of membrane nanostructures leading to the generation of stress signals by combining molecular stress biology and single molecule microscopy. We aim to study the individual variability of membrane nanostructure in isogenic mammalian cell population by combining state of the art ultrasensitive microscopy, lipidomics and proteomics. Since a deregulated stress response is found in a large number of important diseases this study will offer new opportunities for clinical interventions and innovative therapies.
Our specific objectives are to 1) link the population heterogeneity of heat sensing with the membrane nanoscopic organization and dynamics, to 2) elucidate the correlation between membrane composition and structural responsiveness, to 3) identify the sequence of early events during the perception of temperature stress and to 4) identify novel membrane localized sensors.
During the imposition of stress on cells we zoom in on individual cells using ultrasensitive, fluorescent microscopy with a very high spatial and temporal resolution. In parallel with detailed lipidomics and proteomic analysis single molecule microscopy and image fluorescence correlation spectroscopy (ImFCS) is applied. We are optimizing these methods to characterize the cellular individuality of the stress response and of mapping the changes in the composition of plasma membrane enabeling us the identification of the early events of stress sensing- and signaling.
REF: Török, Z. et al. (2014) Plasma membranes as heat stress sensors: From lipid-controlled molecular switches to therapeutic applications. Biochim. Biophys. Acta., 1838:1594-1618.

Recommended language skills: angol
Number of students who can be accepted: 1

Deadline for application: 2016-12-31

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