From physical chemistry to biological systems

The main research activity of Françoise Remacle focusses on molecular logic (see Molecules have logic) and, “ they belong to hard core physical chemistry, like for example the simulation of the response of molecules to very intense and very short laser pulses “, indicates the scientist. “I am doing a lot of research on the how to implement logical operations at a molecular level by targeting and controlling the response of molecules to perturbations which are either photon or electric pulses. This is really the essence of my research activity and in this context I am coordinating the European project MULTI, having already coordinated two other European projects in this area, MOLDYNLOGIC and MOLOC. I am also involved in the European project TOLOP, coordinated by HITACHI the aim of which is to apply these concepts to CMOS-type architecture”, she explains. Besides this, Françoise Remacle is gradually developing another research avenue: the study of phase transitions in biological systems. “I have been in contact with James Heath of the Institute of Technology of California for twenty years and together we have identified phase transitions in physicochemical systems such as networks of metallic quantum dots. It was quite natural for me to continue to collaborate with him by using the same kind of concepts although these were applied to very different systems, and to see to what extent these concepts are relevant and how they make it possible to explain the response to more complex systems”, continues the researcher. The idea is therefore to characterize the response of biological systems to perturbation by using concepts of physical chemistry and thermodynamics which are very different to the methods of statistical analysis which are usually used in biochemistry and medicine. 

A point of balance between two phases

But what is a phase transition? “There is a phase transition for example between liquid water and ice”, explains Françoise Remacle. “ And when we are at the point of balance where water and ice coexist, we cannot change the temperature, even if we supply energy to the system. The temperature will remain at 0°C as long as there is both ice and water at the same time”, explains the scientist. What is involved here then is a very specific point or value in a system of several phases to which the supply of energy will not elicit any response. “This is what we identified in the response to the signalling pathways of mTor”, continues Françoise Remacle. By looking more closely at the response of mTor to variations in oxygen pressure in the cells, researchers have identified a point located somewhere between a level of oxygen pressure of 1.5% and 2%, at which it is impossible to inhibit the activity of mTor. In addition, they showed that hypoxia, that is to say a reduced quantity of oxygen distributed by blood to the tissues, affects and alters the signaling pathway of mTor. “If the oxygen pressure is higher than 2%, mTor is involved in certain types of signaling pathways and when the oxygen pressure is less than 1.5% mTor becomes involved in other signaling pathways”, indicates Françoise Remacle. The results of this study have been published in the journal PNAS (1).

(1) Wei Weia, Qihui Shia, Francoise Remacle, Lidong Qin, David B. Shackelford, Young Shik Shin, Paul S. Mischel, R. D. Levine, James R. Heath. « Hypoxia induces a phase transition within a kinase signaling network in cancer cells » in PNAS, 25/03/201. DOI : 10.1073. Abstract