Job ID: 61632

Pasteur Institute International PhD Programme PPU

Position: Ph.D. Student

Deadline: 28 October 2021

City: Paris

Country: France

Institution: Institut Pasteur

Department:

Description:

Role of human auto-antibodies to nicotinic receptors in neurological and psychiatric disease

Mental disorders are the most debilitating and costly diseases in developed countries. It is estimated that 38.2% of the European population is affected at some point in their lives. For many diseases, no adequate treatments are available. There is a growing realisation that the immune system may be a key player. For example, in a major genome-wide association study (GWAS) linking genetic alterations to schizophrenia, the Major Histocompatibility Complex (MHC) locus was the major “hit” in the genome, far ahead of any genes expressed in the central nervous system.

Psychotic disorders, encompassing schizophrenia (SZ) and bipolar disorders (BD), are major health problems worldwide. Due to their complexity, their heterogeneity and the absence of biomarkers to identify homogeneous subgroups, our understanding of the causes of psychotic disorders remains limited and hence, development of new pathway-related treatment is hampered. However, it is now well-established that immune dysfunction, including auto-immunity, are clearly associated with psychotic disorders opening up new avenues for the discovery of biomarkers, the understanding of mechanisms and the implementation of innovative treatments. Furthermore, the importance of auto-immunity in major psychosis has been strongly reinforced by the association of auto-immune disorders with psychotic disorders and by the discovery of anti-neuronal auto-antibodies (AAbs) that alter synaptic transmission, such as the anti-NMDA receptor antibodies (NMDAR-AAb) in what is called “auto-immune psychosis” . Thus, the role of auto-immunity against neuronal receptor targets in the pathogenesis of psychotic disorders has gained tremendous support (6) over the last years and urgently requires multidisciplinary in-depth investigations to explore new AAbs against brain receptors, to characterise patients carrying these AAbs and to unravel the molecular mechanisms underlying psychosis in order to offer new therapeutic strategies in homogeneous subgroups of patients.