One single neurotransmitter, the amino acid L-glutamate, regulates countless biological systems in animals ranging from worms and insects to human beings.
Interdisciplinary team: Ted Berger (BME); Michel Baudry (LAS); Jean-Marie Bouteiller (BME)
But even though scientists have known for decades that glutamate functions as a neurotransmitter, and have found that numerous diseases, including possibly schizophrenia, are linked to "glutamatergic" transmission malfunctions, no drugs to treat these malfunctions yet exist, despite intense efforts.
Researchers on an interdisciplinary private-academic study hope to learn enough to change this situation, using intensive computer modeling to try to predict synergistic interactions within glutamate systems that might be targets for new drugs.
Michel Baudry (USC College of Letters, Arts and Sciences Department of Biological Sciences), Ted Berger (Viterbi School of Engineering Department of Biomedical Engineering, ), and a French drug discovery company (Rhenovia Pharma) in Mulhouse, France, have been awarded a Biomedical Research Partnership (BRP) by NINDS of the NIH.
Baudry is the PI of the project; Berger is the Co-PI, and Dr. Serge Bischoff is the CEO of Rhenovia Pharma. Successful funding of this proposal is a notable achievement in the sense of the uniqueness of the structure of the research team, and in terms of the novelty of the scientific approach, says Baudry. The grant will support joint research by the three partners for four years, with the total amount of funding reaching $2.3M.
In the lab: Baudry at work.
"This approach will not only provide an intimate understanding of the contribution of specific molecular events to synaptic plasticity and ultimately overall systems function, but also will facilitate the design of better and safer therapeutic strategies for learning and memory impairments."
While the ultimate goal is to enable effective development of drugs, the research proposed is basic understandings, according to Baudry. "The problem with glutamate in terms of pharmaceuticals is that this molecule is absolutely ubiquitous throughout the body. What is therapeutic in one area can be toxic in another. The trick is to find out a way to home in on the specific neural cells you want to affect, without disturbing the others."
Hippocampal cells illuminated to show glutamate activity.
The research to be conducted by the USC and French research teams is centered on a detailed model of glutamatergic synaptic transmission, called EONS, first developed by
Jean-Marie Bouteiller, a Research Assistant Professor working in Dr. Berger's laboratory.
Bouteiller and Berger's research on EONS was, and still is, supported by the USC Biomedical Simulations Resource (BMSR), a Center in the Biomedical Engineering Department of the Viterbi School of Engineering, dedicated to the development of new methods for mathematically modeling physiological systems."
Thus, says Baudry, the collaboration was a "natural," and represents an example of the new emphasis on "translational" science, realized through collaborations that extend to, and include, industry, including researchers at USC, the University Louis Pasteur in Strasbourg, not far from the Mulhouse home of Rhenovia, and engineering and scientific staff at Rhenovia Pharma itself.
Coordination and management are accomplished through weekly conference calls, e-mail, and travel to and from Mulhouse France. In fact, the group just held their first "kick-off" meeting in France to mark the beginning of this trans-Atlantic collaborative effort. This project represents a "bridging of barriers" at the level of disciplines, USC Schools, academia and industry, and the US and the EU.
Glutamate activity in glial cells.
Meetings have so far arrived at the following 'thinking points' regarding the strategy to be used by the USC-Rhenovia team: