Scholar Profile
Abeer Asaly
Supervisor: Prof.
Abdussalam Azem & Dr.
Natalia Borovok
Research Topic:
The Molecular Basis of a Neurodevelopmental Delay Disease that is Associated with a Mutation in the Sec16A Gene
Research Overview:
Recently, our group was involved in the discovery of a new rare disease in a family with two children suffering from a neurodevelopmental genetic disorder characterized by severe intellectual disability, bilateral congenital cataracts, hypotonia, dysmorphic features, and sporadic epilepsy.
Next-generation sequencing analysis revealed that a omozygous variant in the Sec16A gene (NM_001276418.1: c.5309C>T:p.Pro1770Leu) is most probably the cause of the disease in the affected patients. Sec16A plays a key role in ER-Golgi transport, initiating and regulating the assembly of COPII vesicles that facilitate cargo transport in an anterograde manner between the Endoplasmic Reticulum (ER) and Golgi apparatus.
Protein transport and delivery between cellular compartments are essential and evolutionarily conserved processes in all eukaryotic cells. The traffic between the ER and Golgi complex, mediated by coated vesicles, serves
multiple roles in the life cycle of membrane-bound transport intermediates, including lipid bilayer
remodeling, cargo selection, and targeting to an acceptor compartment.
The fact of a homozygous mutation in Sec16A does not provide direct evidence that the mutation is the cause of the disease. The general aim of this study is to uncover the molecular basis of the disease.
We examined the effect of the mutation on the expression of Sec16A and its partner proteins, the interaction of Sec16A with its partner proteins, its effect on cellular localization, and its impact on the cellular proteome. Our results indicate that the mutation in Sec16A affects the normal vesicular transport process.
This research aims to provide valuable insights into the functional significance of Sec16A in maintaining proper protein transport between cellular compartments. By comprehending the cellular consequences of the mutation associated with this neurodevelopmental disease, we can advance our understanding of the disorder's molecular mechanisms. This understanding has the potential to pave the way for targeted therapeutic interventions.