All living cells respond to a non-lethal heat shock by undergoing changes in gene expression. Central to this altered pattern of expression is the induction of a highly conserved group of genes collectively referred to as Heat Shock Genes. In 1988 conventional wisdom had it that heat-induced protein denaturation was the trigger responsible for the induction of the genes responsible for Heat Shock (HS) protein production. However, intrigued by the paradoxical observation that HS gene induction is down regulated as heat shocked cells acclimate to growth at the higher temperature, work in my laboratory concentrated on searched for an alternative explanation to this "heat-induced protein denaturation hypothesis". After some initial resistance our first paper, challenging the accepted paradigm, was accepted for publication in 1993 ( ref.5). In it we demonstrate that the temperature required to trigger the HS response can be altered by as much as 10 0 C by simply altering the percentage of unsaturated fatty acids present in the cell. Since then we have published a series of papers that unequivocally demonstrated that lipids play a vital role in how cells detect stress and in the cross protection of stressing agents with one another (refs 2-4). Moreover, we have recently accumulated evidence that free radicals are also important players in this response (ref.1).

A New Paradigm of Stress Response and Cross-Tolerance. Based on our results it is now apparent that the activation of the HSR trigger is determined, not simply by the temperature, but is also critically dependent upon the type and percentage of unsaturated fatty acids present in the cell. This provides a completely new paradigm for how cells detect and respond to stressful conditions and it also leaves this laboratory uniquely poised to address the fundamental biological question: What is the primary trigger of the cellular HSR? Intriguingly a novel biosensor (see below) currently being developed in collaboration with Dr. Ted VanderNoot, an electrochemist, might just allow us answer this.

Our Heat Shock research strongly suggests that the primary trigger of the Heat Shock Response is intimately associated with a change in the electrochemical gradient across the plasma-membrane. However it is difficult directly to measure these minute changes in electropotential. We are therefore collaborating with Dr. Ted VanderNoot, an electrochemist, in the development of an electronic device that can sense tiny fluctuations in a cell's electrochemical gradient. Uniquely able to monitor cellular metabolism through glass this device reveals cellular activity in real-time. Our prototype device allows us to monitor alcohol toxicity and thermotolerance in yeast, and it has provided for the first time a glimpse of ionic fluxes across the cell membrane during the first few seconds of heat shock. Quite apart from monitoring heat stress, the biosensor has also been used to study light-induced changes in photosynthesis in both single algal cell suspensions and leaf-tissue sections. The device can therefore make valuable contributions to understanding cellular metabolism in a wide variety of biological contexts. We are currently seeking to develop a salt-insensitive version of this device. More details can be found at www.cognitrix.com