Moving towards new cancer therapies with computer simulations at IDSIA USI-SUPSI

From a research hypothesis in experimental biology to the possible application in the field of anticancer therapies, through computer simulations. This is the essential course of an interdisciplinary and international research project that has identified the mechanisms by which particular peptides can penetrate cell membranes and contribute to the elimination of tumors. The study, conducted by the University of Lausanne and involving the research group in computational biophysics of the Dalle Molle Institute of USI and SUPSI, has been published in the prestigious scientific journal PNAS.

In biology, the Cell-Penetrating Peptide (CPP) is a molecule, composed of a few dozens of amino acids, capable of penetrating the cell membrane, which is why it is also called "Trojan peptide". They exist in nature but are also created by humans, and represent an effective method of transferring bioactive molecules into cells. On the mechanisms of this penetration - among other things - Prof. Andrea Danani, head of the Computational Biophysics Group at the Dalle Molle Institute for Artificial Intelligence Studies (IDSIA, a joint USI-SUPSI institute) has been working for several years. "Prof. Christian Widmann of the Department of Physiology at the Faculty of Biology and Medicine, University of Lausanne, involved us to do a few computer simulations to test some hypotheses about the mechanisms governing the penetration into cell membranes of a class of CPPs," Danani explains. "We were able to unravel these mechanisms, allowing them to be successfully tested in the Lausanne labs."

In the context of this collaboration, recent research work involving several institutions in Switzerland, Germany, France and the United States has established how one of these Trojan peptides is able to penetrate cell membranes and selectively lyse cancer cells, without using known cell death programs. "This is a relevant discovery, which paves the way for a possible application of this peptide in existing anticancer therapies," says Prof. Danani.

The research article TAT-RasGAP 317-326 kills cells by targeting inner leaflet-enriched phospholipids is available online at 
www.pnas.org/content/117/50/31871