Human cells produce a variety of proteins, many of which are secreted into the external environment while others are displayed at the cell surface. These proteins are almost always decorated with sugars. Hence, they are called glycoproteins (from the Greek glukus ‘sweet’) and the process by which they are modified with sugars is called glycosylation. The sugar decorations are important for proper protein function as defects cause Congenital Disorders of Glycosylation (CDG) diseases. For example, children with genetic defects in protein glycosylation present diseases with severe symptoms, including failure to thrive, developmental and speech delays, vision loss, seizures, and stroke-like episodes. While certain symptoms can be treated there is no cure. For these reasons, it is important to understand exactly how proteins are decorated with sugars at the endoplasmic reticulum (ER), a membrane compartment inside the cell.
The goal of my Gateway Fellowship project at Weill Cornell Medical College is to elucidate the molecular function of the membrane protein RFT1 which is known to be involved in the first part of the glycosylation pathway that occurs in the ER. Mutations in RFT1 causes CDG, but the underlying molecular defect is not well understood. I will use a suite of state-of-the-art methods to test my hypothesis that RFT1 is a lipid binding protein that is critical for glycosylation. My results should help us to understand the basis of CDG caused by RFT1 deficiency and thus formulate therapies.
My PhD thesis was about parameters of human brain physiology that can be modulated with non-invasive brain stimulation (NIBS) techniques. The application of NIBS in neuropsychiatric disorders has recently attracted much attention and is very promising considering its fewer side effects. Schizophrenia is a brain disorder marked with pervasive cognitive deficits and brain functional abnormalities. Few studies have applied NIBS in schizophrenia but the underlying mechanisms of the effects are not well-known. Combining neuroimaging methods (fMRI) with NIBS techniques is among the most sophisticated methods in human neuroscience and allows us to investigate the underlying mechanism of effects. Very few labs worldwide have the facilities for conducting such research. The NINET lab at the University of British Columbia (UBC) and the NBML at the University of Tehran are among those labs and will be my host institutes during my gateway fellowship. The NINET lab, which is supervised by Dr. Fidel Vila-Rodriguez at UBC, provides the analytical and methodological support for this project and the NBML is where the data will be collected as access to the target patients and required facilities is more feasible. I am very delighted that the gateway fellowship provides the opportunity for me to conduct one of my favorite and at the same time timely research questions in the NENET lab and NBML. The flexibility of the fellowship that allows doing multicenter research projects abroad is quite unique and very helpful for early-career researchers.