Yin Yao Dong
MRC Career Development Fellow
- Principal Investigator
N-glycosylation and its importance to neuromuscular junctions
N-glycosylation is one of the most common forms of post-translational modification, and is present on most membrane and secreted proteins. It is essential to all eukaryotic life, yet we know little about the function of the vast majority of N-linked glycans. Mutations that lead to abnormalities in N-glycosylation can lead to the devastating multisystem disorder Congenital Diseases of Glycosylation (CDG) or the milder Congenital Myasthenic Syndromes (CMS), where patients mainly suffer from dysfunctional neuromuscular junctions.
The focus of my group's research is to better understand the process of N-glycosylation, and why abnormalities in this ubiquitous process can lead to the specific dysfunction in neuromuscular junctions. To achieve this, we use a multidisciplined approach combining techniques in biochemistry, structural biology, molecular biology and glycomics.
N-glycosylation at the neuromuscular junction (NMJ)
The aim of this project is to study the effects of disease associated mutations on the N-glycosylation of proteins known to be important to the development and function of the NMJ. Students working on this project will learn to use gene editing, cell culture, molecular biology and protein purification. This project will be co-supervised by Prof David Beeson of NDCN, and will involve collaboration with Dr Stuart Haslam of Imperial College who's group will conduct glycomic and glycoproteomic analysis of purified samples.
Structure and function of N-glycosylation enzymes
The focus of this project is to use a combination of structural biology and biochemistry to study the structure and function of enzymes involved in N-glycosylation, and create a model system to study and treat disease associated mutations. This project will be co-supervised by Prof Liz Carpenter at the Structural Genomics Consortium.
Fundamental biochemistry of N-glycosylation
The focus of this project is to better understand the mechanism and kinetics of N-glycosylation enzymes. This involves the large scale expression and purification of enzymes, and the chemical synthesis of the complex glycans and glycolipids. The mechanism and kinetics of the enzymes will then be assessed using biochemical methods and mass spectrometry. This project will be co-supervised by Prof Ben Davis of the Department of Chemistry.