Exploring the DISC1-VGF connection in chronic mental illness
Daniela Moutinho (daniela.moutinho@usc.es)
Supervisor: Jesus Requena, PhD (jesus.requena@usc.es)
CIMUS Biomedical Research Institute, University of Santiago de Compostela, Spain
I am a Bachelor of Molecular Cell Biology and a Master of Molecular Genetics and Biomedicine both from the Universidade Nova de Lisboa in Portugal. My master thesis involved the crystallization of a human protein, ceruloplasmin, in combination with neurotransmitters, which can be related to neurodegenerative disorders, such as Alzheimer’s or Parkinson’s diseases.
Before I started my PhD I have worked in several projects involving infectious and genetic human diseases. I have worked in a project involving the modulation of the immunogenic and antigenic properties of Human Immunodeficiency Virus envelope polypeptides by sialylation for six months. I dedicated the next years studying the Antley-Bixler Syndrome related mutations of cytochrome P450 oxidoreductase and for 1 year and a half I have been working for Merck Serono Company in several projects concerning the crystallization of human proteins with biomedical interest for further structural studies and drug design.
As a part of the INSENS training network I aim to study the role of the neuropeptide VGF and the protein DISC1 in chronic mental illness. DISC1 regulates the expression of VGF, which has potent antidepressant properties, and it is thought that some of the roles of DISC1 deficits in mental disease might be mediated by reduced expression of VGF. I aim to investigate the molecular mechanisms of this pathway at a molecular, cellular and behavioral level using expression constructs, neuronal cells and animal models. In particular, I will try to elucidate the signaling pathways connecting DISC1 and VGF, to identify VGF receptors and develop receptor agonists, and to study the effect of VGF-derived peptides and VGF receptor agonists on behavioral deficits of DISC1-deficient mouse models. I will also try to pursue the tridimensional structure of VGF, as it can be of great value when trying to understand its role at molecular and cellular level, and in the search for possible receptor agonists for treatment of some neurological diseases as depression or schizophrenia.
