OSTers · Role of OligoSaccharyl Transferase enzymes in developmental signaling and congenital disorders of glycosylation

Role of OligoSaccharyl Transferase enzymes in developmental signaling and congenital disorders of glycosylation

The action” Role of OligoSaccharyl Transferase enzymes in developmental signaling and congenital disorders of glycosylation” focuses on genetic defects affecting the assembly and addition of (N)-glycans to proteins. N-glycosylation occurs in a dedicated compartment of the cells, the endoplasmic reticulum, by the Oligosaccharyl transferase (OST) complex. This work investigated what is the molecular mechanism by which mutations in OST complex cause abnormal phenotypes in animal development to decipher some aspects of patients’ clinical features with Congenital disorders of glycosylation (CDGs). The fellow conducting this research paid particular interest in the basic biology of glycosylation-related genes and how they affect protein folding, protein trafficking, and ultimately cell signaling. Recent advances in genome sequencing technologies are increasing the pace of discovery for new types of genetic diseases associated with glycosylation, opening questions on the biological relevance of the enzymes involved in the glycosylation machinery and how the disruption of such genes results in disease remains a constant challenge. Given the unknown nature of pathogenesis of the glycosylation-linked diseases, the research conducted in this MSCA action provides a link between the basic biology of glycosylation and clinical features of CGD patients for allowing the transfer of research knowledge to clinical practice. Importantly, understanding the role of glycosylation genes in cell functions offers useful insights not only for future therapies of CDG patients but also for patient stratification and monitoring, such as in cancer, nutrition, and immunology fields. Objectives of this Marie Skłodowska Curie Action (MSCA) have been to (a) characterize and compare the roles of OST complex during development in disease models; (b) understand the molecular basis for the regulation of developmental signaling pathway by N-glycosylation; (c) characterize the dysregulation of OST complex in mammalian cell models and OST-linked diseases. As a personal objective, the MSCA Individual Fellowship (MSCA-IF) has developed my potential for an advanced career, both in academic and entrepreneurial sectors connected to congenital rare diseases. Therefore MSCA-IF helped me to establish new collaborations with prominent scientists, with special attention to the Italian network, along with patient associations in the spirit of a synergic knowledge-building environment.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз