BACKGROUND

Jose Ramon Bayascas was born and educated in Barcelona, were he graduated in Biological Sciences from the University of Barcelona in 1992 and received a Ph.D. in Biological Sciences in 1998 under the supervision of Professor Emili Saló, University of Barcelona. He then carried out postdoctoral research for nine years, first with Professor Joan Comella at the University of Lleida from 1998 to 2002, and then with Professor Dario Alessi at the University of Dundee, Scotland, from 2002 to 2007, were he became proficient in the analysis of cell signaling in metabolism, cancer and neurobiology. In 2007 he joined the Departament de Bioquímica i Biologia Molecular of the Universitat Autònoma de Barcelona, were he has leadershipping a new Institut de Neurociencies research team ever since, first as a Ramon y Cajal Fellow and from October 2014 as a Serra Húnter Associate Professor. His current research aims to define the neurodevelopmental functions of the PDK1 signaling network and its consequences to neurodegenerative and mental illness.

STRATEGIC OBJECTIVES

The research activity of our group aims to understand the importance that the dysfunction of the mechanisms of signal transduction might play in brain pathology. The group focussed on the PI 3-kinase/Akt signaling pathway, which controls essential roles during neuronal development and is deregulated in different mental disorders. We generated brain-specific conditional knock-in mice expressing two distinct rationally designed, crystal structure-based, point mutant forms of the PDK1 kinase, a master hub on this signaling pathway. In the PDK1 K465E mice, activation of Akt is selectively impaired, whereas in the PDK1 L155E mice, activation of most of the effectors of this signaling axis including S6K, RSK, SGK, and PKC, but not Akt, is abolished. These mice become instrumental to define the neurodevelopmental functions of the PDK1 signalling network and its consequences to neurodegenerative and mental disease.

MAIN RESEARCH LINES

1) To investigate whether the PDK1 K465E mice are protected from Alzheimer Disease. In the PDK1 K465E knock-in mice, reduced activation of Akt caused subtle morphogenetic defects that did not lead however to adverse behavioral outputs. We learned that the hypomorphic reduction of the Akt axis protected these mice from a number of insults disrupting homeostasis, which might singularly be also protected from neurodegeneration.

 2) To define the contribution of the PDK1 substrates different from Akt to mental disease. In the PDK1 L155E mice, the normal and exclusive activation of Akt among the different PDK1 substrates caused profound defects in the patterning of the central nervous system, leading to severe mental disorders reminiscent of human schizophrenia.